Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication CABENUVA is indicated as a complete regimen for the treatment of HIV-1 infection in adults and adolescents 12 years of age and older and weighing at least 35 kg to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or… FDA label
Also known as CAB LA, CAB ULA, Cabotegravir long-acting, Cabotegravir (CAB) tablet, Cabotegravir - Injectable Suspension (CAB LA), Cabotegravir- Injectable, Cabotegravir Tablets, Cabotegravir Injectable Suspension
Cabotegravir · 25 trials · 4 indications
A virologic suppression is defined by HIV-1 RNA less than (\<) 50 copies (c)/mL.
Relevant characteristics of new HIV infections will be assessed, including presence of viral resistance to CAB.
Blood samples were collected at indicated time points for PK analysis.
Blood samples were collected at indicated time points for PK analysis.
Blood samples were collected at indicated time points for PK analysis.
Blood samples were collected at indicated time points for PK analysis.
Blood samples were collected at indicated time points for PK analysis.
Blood samples were collected at indicated time points for PK analysis.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis.
Blood samples were collected for PK analysis.
Blood samples were collected for PK analysis.
Blood samples were collected for PK analysis.
Blood samples were collected for PK analysis.
Blood samples were collected for PK analysis.
Blood samples were collected for PK analysis.
Blood samples were collected for PK analysis.
Blood samples were collected for PK analysis.
Blood samples were collected for PK analysis.
Blood samples were collected for PK analysis.
Blood samples were collected for PK analysis.
Percentage of participants with plasma HIV 1 RNA \>= 50 c/mL at month 12 was assessed using the food and drug administration (FDA) snapshot algorithm. For the Q2M arm, data from the Q2M OLI participants at Month 12 visit and Q2M D2I participants at Month 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 12 visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL), along with study drug discontinuation status. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.
Percentage of participants with plasma HIV 1 RNA \>= 50 c/mL at month 12 was assessed using the food and drug administration (FDA) snapshot algorithm. For the Q2M arm, data from the Q2M OLI participants at Month 12 visit and Q2M D2I participants at Month 11 visit were combined as the study objective was to demonstrate the non-inferior antiviral activity of (Q2M) (OLI+ D2I combined) compared to BIK. For BIK arm, data was collected at month 12 visit. Month 12/11 refers to the Month 12 (OLI and BIK) visit/Month 11 (DTI) visit. The FDA snapshot algorithm defines a participant's virologic response status using only the viral load at the predefined time point within a window of time (HIV-RNA equal to or above 50 copies/mL and HIV-RNA below 50 copies/mL), along with study drug discontinuation status. The third category of the FDA snapshot ("No virologic data") is not pre-defined as an endpoint and therefore not reported separately.
AIM is a four item survey that assessed the acceptability of an implementation process. The staff study participants were asked to indicate how much they agreed or disagreed with each of the 4 items in the AIM based on their current experiences with implementing the CAB + RPV injection treatment on a five point rating scale (1=completely disagree to 5=completely agree). The AIM total score ranges from 1 to 5 with 1 indicating the least acceptability and 5 the most acceptability. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
AIM is a four item survey that assessed the acceptability of an implementation process. The staff study participants were asked to indicate how much they agreed or disagreed with each of the 4 items in the AIM based on their current experiences with implementing the CAB + RPV injection treatment on a five point rating scale (1=completely disagree to 5=completely agree). The AIM total score ranges from 1 to 5 with 1 indicating the least acceptability and 5 the most acceptability. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
AIM is a four item survey that assessed the acceptability of an implementation process. The participants were asked about their impressions of the CAB LA + RPV LA injection treatment for treating HIV on a five point rating scale (1=completely disagree to 5=completely agree). The AIM total score ranges from 1 to 5 with 1 indicating the least acceptability and 5 the most acceptability. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
AIM is a four item survey that assessed the acceptability of an implementation process. The participants were asked about their impressions of the CAB LA + RPV LA injection treatment for treating HIV on a five point rating scale (1=completely disagree to 5=completely agree). The AIM total score ranges from 1 to 5 with 1 indicating the least acceptability and 5 the most acceptability. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
IAM is a four item survey that assessed the appropriateness of an implementation process. The staff study participants were asked to indicate how much they agreed or disagreed with each of the 4 items in the IAM based on their current experiences with implementing the CAB + RPV injection treatment on a five point rating scale (1=completely disagree to 5=completely agree). The IAM total score ranges from 1 to 5 with 1 indicating the least appropriateness and 5 the most appropriateness. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
IAM is a four item survey that assessed the appropriateness of an implementation process. The staff study participants were asked to indicate how much they agreed or disagreed with each of the 4 items in the IAM based on their current experiences with implementing the CAB + RPV injection treatment on a five point rating scale (1=completely disagree to 5=completely agree). The IAM total score ranges from 1 to 5 with 1 indicating the least appropriateness and 5 the most appropriateness. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
IAM is a four item survey that assessed the appropriateness of an implementation process. The participants were asked to indicate how much they agreed or disagreed with each of the 4 items in the IAM based on their current experiences with implementing the CAB + RPV injection treatment on a five point rating scale (1=completely disagree to 5=completely agree). The IAM total score ranges from 1 to 5 with 1 indicating the least appropriateness and 5 the most appropriateness. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
IAM is a four item survey that assessed the appropriateness of an implementation process. The participants were asked to indicate how much they agreed or disagreed with each of the 4 items in the IAM based on their current experiences with implementing the CAB + RPV injection treatment on a five point rating scale (1=completely disagree to 5=completely agree). The IAM total score ranges from 1 to 5 with 1 indicating the least appropriateness and 5 the most appropriateness. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
FIM is a four item survey that assessed the feasibility of an implementation process. The staff study participants were asked to indicate how much they agreed or disagreed with each of the 4 items in the FIM based on their current experiences with implementing the CAB + RPV injection treatment on a five point rating scale (1=completely disagree to 5=completely agree). The FIM total score ranges from 1 to 5 with 1 indicating the least feasibility and 5 the most feasibility. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
FIM is a four item survey that assessed the feasibility of an implementation process. The staff study participants were asked to indicate how much they agreed or disagreed with each of the 4 items in the FIM based on their current experiences with implementing the CAB + RPV injection treatment on a five point rating scale (1=completely disagree to 5=completely agree). The FIM total score ranges from 1 to 5 with 1 indicating the least feasibility and 5 the most feasibility. Baseline is defined as the latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.
Percentage of participants with HIV-1 RNA \>=50 c/mL as per FDA snapshot algorithm at Week 48 was assessed to demonstrate the non-inferior antiviral activity of CAB LA+RPV LA Q8W compared to CAB LA + RPV LA Q4W regimen over 48 weeks in HIV-1 infected ART experienced participants. The HIV-1 RNA \>=50 c/mL per Snapshot algorithm was determined by the last on-treatment HIV-1 RNA measurement within the Week 48 analysis visit window. Intent-to-treat-Exposed (ITT-E) Population comprised of all randomized participants who received at least one dose of study treatment. Participants were assessed according to their randomized treatment, regardless of the treatment they received.
Number of participants with virologic failure endpoint (HIV-1 RNA\>=50 c/mL) as per Food and Drug Administration (FDA) snapshot algorithm at Week 48 was assessed to demonstrate the non-inferior antiviral activity of switching to intramuscular (IM) CAB LA+RPV LA every 4 weeks compared to continuation of current ART regimen over 48 weeks in HIV-1 infected ART-experienced participants. The HIV-1 RNA \>=50 copies/mL per snapshot algorithm was determined by the last available on-treatment HIV-1 RNA measurement within the analysis visit window of interest.
Percentage of participants with virologic failure endpoint (HIV-1 RNA\>=50 c/mL) as per Food and Drug Administration (FDA) snapshot algorithm at Week 48 was assessed to demonstrate the noninferior antiviral activity of switching to intramuscular (IM) CAB LA+RPV LA every 4 weeks compared to continuation of ABC/DTG/3TC regimen over 48 weeks in HIV-1 infected ARTexperienced participants. The HIV-1 RNA \>=50 copies/mL per snapshot algorithm was determined by the last on-treatment HIV-1 RNA measurement within the Week 48 analysis visit window (+/- 6 weeks) or at time of discontinuation (if discontinuation occurred prior to Week 48 for reasons other than Adverse Event).
CAB trough concentrations are evaluated at or above the target of 1.05 μg/mL for men and 1.39 μg/mL for women, once steady state has been achieved, but no earlier than Month 13 of the study.
Feasibility of CDTM+ assessed using the Intervention Measure: 4-item Likert scale, each item scored 1 (completely disagree) to 5 (completely agree) and averaged. Score range 4-20, higher scores reflect higher feasibility.
Assessed using the Theoretical Framework of Acceptability Questionnaire: 7-items, each scored on Likert scale 1 to 5 and averaged. Score range 7-35, higher scores reflect higher acceptability.
Assessed by the percentage of patients who have a documented 1st injection visit
Percentage of participants with HIV-1 RNA \>=50 c/mL as per FDA snapshot algorithm at Month 12 was assessed to demonstrate the antiviral activity of CAB LA+RPV LA Q2M and DTG + RPV regimen in HIV-1 infected antiretroviral therapy (ART) experienced participants. The HIV-1 RNA \>=50 c/mL per Snapshot algorithm was determined by the last on-treatment HIV-1 RNA measurement within the 12 months analysis visit window.
Percentage of participants with HIV-1 RNA\<50 c/mL was obtained using Food and Drug Administration (FDA) Snapshot algorithm. The algorithm treated all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) as well as participants who switch their concomitant antiretroviral therapy (ART) prior to the visit of interest as non-responders. The Intent-to-Treat Maintenance Exposed (ITT-ME) Population consisted of all randomized participants who received at least one injection or one dose of investigational product during the Maintenance Period of the study (on or after Day 1 visit).
Virologic failure was defined as any of the following: (1) Non-response as indicated by a less than 1.0 logarithm to base 10 (log10) c/mL decrease in plasma HIV-1 RNA after 4 weeks of starting the Induction Period, which is subsequently confirmed, unless the plasma HIV-1 RNA is \< 400 c/mL; (2) Rebound as indicated by two consecutive plasma HIV-1 RNA levels \>=200 c/mL after prior suppression to \< 200 c/mL; (3) Rebound as indicated by two consecutive plasma HIV-1 RNA that are \> 0.5 log10 c/mL increase in plasma HIV-1 RNA from the nadir value on study, where the lowest HIV-1 RNA value is \>=200 c/mL.
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, important medical events which may require medical or surgical intervention, drug-induced liver injury with hyperbilirubinaemia.
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, important medical events which may require medical or surgical intervention, drug-induced liver injury with hyperbilirubinaemia. Data presented includes all post-baseline induction period and maintenance period adverse events, as well as long-term follow-up period adverse events for those participants who did not enter the extension period.
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Toxicity was graded according to Division of Acquired Immunodeficiency Syndrome (DAIDS) grading criteria, where Grade 1-mild, Grade 2-moderate, Grade 3-severe, Grade 4-potentially life-threatening. Data presented includes all post-baseline treatment emergent Induction Period and MP toxicities, as well as LTFP toxicities for those participants who did not enter the extension period. Number of participants with post-Baseline adverse events by maximum toxicity Grade have been presented.
Clinical chemistry parameters aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), carbon dioxide(CO2) content/bicarbonate (HCO3), cholesterol, creatine kinase (CK), glucose, low density lipoprotein (LDL) cholesterol, lipase, potassium, and sodium, total bilirubin (TBIL) and triglycerides were evaluated. Toxicity was graded according to Division of Acquired Immunodeficiency Syndrome (DAIDS) grading criteria, where Grade 1-mild, Grade 2-moderate, Grade 3-severe, Grade 4-potentially life-threatening. Data presented includes all post-baseline treatment emergent Induction Period and MP toxicities, as well as LTFP toxicities for those participants who did not enter the extension period. Number of participants with any time post-baseline maximum emergent toxicities in any of the chemistry parameters have been presented.
Hematology parameters hemoglobin, platelet count, total neutrophils and white blood cell count were evaluated. Toxicity was graded according to DAIDS grading criteria, where Grade 1-mild, Grade 2-moderate, Grade 3-severe, Grade 4-potentially life-threatening. Data presented includes all post-baseline treatment emergent Induction Period and MP toxicities, as well as LTFP toxicities for those participants who did not enter the extension period. Number of participants with any time post-baseline maximum emergent toxicities in any of the hematology parameters have been presented.
Urinalysis dipstick included urine occult blood, urine glucose, urine ketones, urine nitrite, urine protein and urine leukocyte. The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters can be read as positive, trace, 1+, 2+ and 3+ indicating proportional concentrations in the urine sample. Data presented includes all post-baseline dipstick results during Induction and Maintenance Periods, as well as LTFP for those participants who did not enter the extension period.
Blood samples are collected at specific time points for PK analysis to determine Cmax.
Blood samples are collected at specific time points for PK analysis to determine Cmax.
Blood samples are collected at specific time points for PK analysis to determine Clast.
Blood samples are collected at specific time points for PK analysis to determine Clast.
Blood samples are collected at specific time points for PK analysis to determine AUC0-t.
Blood samples are collected at specific time points for PK analysis to determine AUC0-t.
Blood samples are collected at specific time points for PK analysis to determine C0h.
Blood samples are collected at specific time points for PK analysis to determine C0h.
Blood samples are collected at specific time points for PK analysis to determine post-dose concentrations.
Blood samples are collected at specific time points for PK analysis to determine post-dose concentrations.
A drug-related AE is any untoward medical occurrence in a clinical study participant considered related to the study intervention. The severity of events is graded using the DAIDS grading scale, where grades are defined based on numeric criteria as follows: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = potentially life-threatening. A higher grade indicates greater severity.
An SAE is defined as any untoward medical occurrence that is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or results in death. The severity of events is graded using the DAIDS grading scale, where grades are defined based on numeric criteria as follows: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = potentially life-threatening. A higher grade indicates greater severity.
An ISR is defined as an adverse event which is localized at the injection site, typically includes pain, tenderness, erythema, redness, induration, swelling, nodules or pruritus, but may also encompass other reactions. The severity of events is graded using the DAIDS grading scale, where grades are defined based on numeric criteria as follows: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = potentially life-threatening. A higher grade indicates greater severity.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention.
The analysis is performed using the 21-item perception of injection (PIN) questionnaire which includes 21 items grouped into 4 multi-item domains: 'Acceptance of ISR' scale score (2 items); 'Bother from ISR' scale score (6 items); 'Leg movement' scale score (4 items); 'Sleep' scale score (4 items); and 5 standalone items: pain during injection; anxiety before injection; anxiety after injection; willingness to be injected in the future; and overall satisfaction with mode of administration. Participant responses are scored on a 5-point Likert scale, where 1 represents the least favorable perception of injection and 5 the most favorable, with domain scores calculated as the mean of all items in that domain. "Acceptance of ISR" is reported in this outcome measure for 2 scores: "very acceptable ISR: and "totally acceptable ISR".
Clinical chemistry parameters such as Aspartate Aminotransferase (AST) / Serum Glutamic-Oxaloacetic Transaminase (SGOT), Alanine Aminotransferase (ALT)/ Serum Glutamic-Pyruvic Transaminase and (SGPT), Alkaline phosphatase (ALP) and Creatinine Phosphokinase (CPK) will be analyzed.
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of CAB.
Blood samples were collected at indicated time points for PK analysis of RPV.
Blood samples were collected at indicated time points for PK analysis of CAB.
Blood samples were collected at indicated time points for PK analysis of RPV.
Blood samples were collected at indicated time points for PK analysis of CAB.
Blood samples were collected at indicated time points for PK analysis of RPV.
Blood samples were collected at indicated time points for PK analysis of CAB.
Blood samples were collected at indicated time points for PK analysis of RPV.
Blood samples were collected at indicated time points for PK analysis of CAB.
Blood samples were collected at indicated time points for PK analysis of RPV.
Blood samples were collected at indicated time points for PK analysis of CAB.
Blood samples were collected at indicated time points for PK analysis of RPV.
Blood samples were collected for Pharmacokinetic (PK) analysis of CAB. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Blood samples were collected for PK analysis of CAB. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Blood samples were collected for PK analysis of CAB after intramuscular (IM) administration. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Blood samples were collected for PK analysis of CAB after intramuscular (IM) administration. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Blood samples were collected for PK analysis of CAB after intramuscular (IM) administration. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
KALA defined as the rate at which a drug is absorbed into the bloodstream after administration. Blood samples were collected at indicated time points. PK parameters were determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
KALA defined as the rate at which a drug is absorbed into the bloodstream after administration. Blood samples were collected at indicated time points. PK parameters were determined using standard non-compartmental methods. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Blood samples were collected for PK analysis of CAB. Ctau is the trough concentration at the end of the dosing interval. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze and compare the data for participants that received CAB 400 mg/ml formulation in this study, and historical data for CAB 200 mg/mL in ATLAS /FLAIR studies.
Blood samples were collected for PK analysis of CAB. Ctau is the trough concentration at the end of the dosing interval. PK parameter was determined using standard non-compartmental methods. The objective of this endpoint was to analyze and compare the data for participants that received CAB 400 mg/ml formulation in this study, and historical data for CAB 200 mg/mL in ATLAS /FLAIR studies.
Blood samples were collected for PK analysis of CAB. PK parameter was determined using standard non-compartmental methods. Ctau is the trough concentration at the end of the dosing interval. Ctau was expressed as geometric mean. For ATLAS /FLAIR: Historical data of CAB200 group, the geometric mean following dose normalization to 800mg was presented. The objective of this endpoint was to analyze and compare the data for participants that received CAB 400 mg/ml formulation in this study, and historical data for CAB 200 mg/mL in ATLAS /FLAIR and ECLAIRE studies.
Blood samples were collected for PK analysis of CAB. The PK parameters were calculated by non-compartmental analysis. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
Blood samples were collected for PK analysis of CAB. The PK parameters were calculated by non-compartmental analysis. The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
The objective of this endpoint was to analyze data for participants that received CAB 400 mg/ml formulation, therefore results are presented for those groups only.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, or other situations as per investigator's judgement.
Hematology parameters were graded according to Division of Acquired Immunodeficiency Syndrome (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events as Grade 0: none, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Higher grade indicates more severity. Clinical hematology parameters included: Activated partial thromboplastin time (APTT) prolonged, hemoglobin (Hb) (increased), white blood cells (WBC) (decreased), lymphocytes count (decreased), neutrophils (decreased), platelets (decreased), prothrombin international normalized ratio (Pro.INR) (increased). Baseline was the last available assessment prior to the time of the first dose. Maximum toxicity grade reached by a participant post-Baseline was summarized.
Chemistry parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events as Grade 0: none, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Higher grade indicates more severity. Clinical chemistry laboratory parameters included alanine amino transferase (ALT), albumin, alkaline phosphatase (ALP), Aspartate Aminotransferase (AST), bilirubin, calcium (hypercalcemia and hypocalcemia), carbon dioxide (CO2) (decreased), cholesterol (high), Creatine phosphokinase (CPK) increased, Creatinine increased, creatinine clearance (decreased), glucose (hyperglycemia and hypoglycemia), Hypophosphatemia, Potassium (Hyperkalemia and hypokalemia), Sodium (hypernatremia and hyponatremia), Hypertriglyceridemia, uric acid (increased). Baseline was the last available assessment prior to the time of the first dose. Maximum toxicity grade reached by a participant post-Baseline was summarized.
Urinalysis parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events as Grade 0: none, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Urinalysis parameters included: Protein. Baseline was the last available assessment prior to the time of the first dose. Maximum toxicity grade reached by a participant post-Baseline was summarized.
Vital signs were measured after participants had rested in supine position for at least 5 minutes. Clinical concern ranges were: systolic blood pressure (SBP) (Low: \<85 millimeters of mercury \[mmHg\], High: \>160 mmHg), diastolic blood pressure (DBP) (Low: \<45 mmHg, High: \>100 mmHg), pulse rate (Low: \<40 mmHg, High: \>100 mmHg). Worst case results are presented. Participants were counted in the worst case category that their value changes to (Low, Normal or High), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Number of participants withdrawn from study due to AEs is presented.
Injection site reactions were recorded via ISR diaries and managed through investigator assessment. Number of participants who experienced any injection site reaction (like pain, itching, bruising, bump, discoloration, redness, skin firmness, swelling, warm to touch etc.) is presented.
Blood samples were collected at the indicated time points for the determination of Ctau following oral dose of Cabotegravir and was calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for the determination of AUC(0-tau) following oral dose of Cabotegravir and was calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for the determination of Cmax following oral dose of Cabotegravir and was calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for the determination of Tmax following oral dose of Cabotegravir and was calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for the determination of CL/F following oral dose of Cabotegravir and was calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for the determination of t1/2 following oral dose of Cabotegravir and was calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for the determination of Lambda z following oral dose of Cabotegravir and was calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for the determination of Vss following oral dose of Cabotegravir and was calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for the determination of Ctau following IM dose of CAB LA and was calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for the determination of AUC (0-tau) following IM dose of CAB LA and was calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for the determination of Cmax following IM dose of CAB LA and was calculated by standard non-compartmental analysis.
Blood samples were collected at the indicated time points for the determination of Tmax following IM dose of CAB LA and was calculated by standard non-compartmental analysis.
Blood samples for PK analysis of CAB were collected at pre-dose (within 15 minutes prior to dose) on Days 13 and 14; and 1, 2, 3, 4, 8, 12, and 24 hours post-dose on Day 14, pre-dose (within 15 minutes prior to dose) on Days 26, 27 and 28; and 1, 2, 3, 4, 8, 12 and 24 hours post-dose on Day 28. AUC (0 to tau) was calculated using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid. PK Summary Population included participants who had CAB PK parameter estimates from both serial PK sampling time periods 1 and 2. Comparisons were made for the repeated dose PK parameters of CAB when given alone in Period 1 and when co-administered with steady-state RBT in Period 2.
Blood samples for PK analysis of CAB were collected at pre-dose (within 15 minutes prior to dose) on Days 13 and 14; and 1, 2, 3, 4, 8, 12, and 24 hours post-dose on Day 14, pre-dose (within 15 minutes prior to dose) on Days 26, 27 and 28; and 1, 2, 3, 4, 8, 12 and 24 hours post-dose on Day 28. Cmax was determined directly from the concentration-time data. Comparisons were made for the repeated dose PK parameters of CAB when given alone in Period 1 and when co-administered with steady-state RBT in Period 2.
AUC (0 infinity\[inf\]) is defined as the area under cabotegravir plasma concentration time curve from time zero (pre dose) extrapolated to infinite time.
AUC (0-t) is defined as area under cabotegravir plasma concentration time curve from time zero (pre dose) to the last time of quantifiable concentration.
Cmax is defined as the maximum observed plasma concentration of cabotegravir.
C24 is defined as the plasma concentration at 24 hours after administration of cabotegravir.
Plasma PK samples collected at the following time points: Period 1 pre-dose (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours post dose. Period 3 pre-dose Day 21 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours (Day 8) post dose.
Plasma PK samples collected at the following time points: Period 1 pre-dose (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours post dose. Period 3 pre-dose Day 21 (within 15 minutes prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 (Day 3), 72 (Day 4), 120 (Day 6), 168 hours (Day 8) post dose.
To evaluate the relative bioavailability of cabotegravir after single 30 mg dose in the fasted state, the following PK parameters will be assessed: area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC(0-infinity)), area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC (0-t)), maximum observed concentration (Cmax) and concentration at 24 hours post-dose (C24)
| Arm | Type | Description |
|---|---|---|
| CAB ULA+ RPV ULA | EXPERIMENTAL | Participants will receive CAB ULA+RPV ULA. |
| CAB LA+ RPV LA | ACTIVE_COMPARATOR | Participants will receive CAB LA+RPV LA. |
| CAB LA + RPV LA Group | EXPERIMENTAL | Participants receive initial injections at Day 1 and Month 1, followed by maintenance injections every 2 months for up to 24 months. |
| Oral ART Control Group | ACTIVE_COMPARATOR | Participants continue to take their current oral ART for 6 months, including a final dose at their first injection visit. |
| CAB LA 600 mg (Q8W) | EXPERIMENTAL | All enrolled participants have previously received CAB LA as part of the HPTN 083 and HPTN 084 parent studies or their sub-studies. Participants will continue receiving CAB LA 600 mg via gluteal intramuscular (IM) injection. |
| Cabotegravir Long Acting (CAB LA) 400 Milligrams (mg) + Rilpivirine Long Acting (RPV) LA 600 mg | EXPERIMENTAL | Participants received an intramuscular (IM) injection of CAB LA 400 mg and RPV LA 600 mg on week -4 during the Screening phase. Participants then received a sub-cutaneous (SC) injection of CAB LA 400 mg + RPV LA 600 mg on Day 1 of Week 1, Week 4 and Week 8 (once in every 4 weeks (Q4W)) for a total of 12 weeks during the SC abdominal Injection Phase. 4 weeks later, participants returned to the clinic for an IM gluteal injection (at Week 12) of CAB LA 400 mg + RPV LA 600 mg during the Return to Gluteal Injection Phase and subsequent gluteal injection occurred after Q4W at Week 16. |
| Participants receiving CAB LA 400 milligrams (mg) and RPV LA 600 mg | EXPERIMENTAL | Participants will receive an Intramuscular (IM) injection of CAB LA 400 mg on one lateral thigh and RPV LA 600 mg into the opposite lateral thigh on Day 1 in every 4 weeks (Q4W) for a total of 16 weeks during Thigh injection phase. Participants will then return to the clinic 4 weeks later to receive their first IM gluteal injection (at Week 16) of CAB LA 400 mg and RPV LA 600 mg during the Return to Gluteal Injection Phase. The subsequent gluteal injection will occur at Week 20. |
| Participants receiving CAB LA 600 mg and RPV LA 900 mg | EXPERIMENTAL | Participants will receive an IM injection of CAB LA 600 mg on one lateral thigh and RPV LA 900 mg into the opposite lateral thigh on Day 1 in every 8 weeks (Q8W) for a total of 16 weeks during Thigh injection phase. Participants will then return to the clinic 8 weeks later receive their first IM gluteal injection (at Week 16) of CAB LA 600mg and RPV LA 900 mg during the Return to Gluteal Injection phase. The subsequent gluteal injection will occur at Week 24. |
| Biktarvy (BIK) | ACTIVE_COMPARATOR | Participants with HIV-1 received BIK tablet orally until month 12. BIK was a fixed dose combination of 50 mg Bictegravir (BIC) + 200 mg Emtricitabine (FTC) + 25 mg Tenofovir alafenamide (TAF). |
| Oral lead-in phase (OLI) | EXPERIMENTAL | Participants with human immunodeficiency viruses (HIV)-1 who chose oral lead in (OLI) received oral 30 milligram (mg) Cabotegravir (CAB) tablet + 25 mg Rilpivirine (RPV) tablet once daily (QD) for one month. At the month 1 visit, the last dose of oral CAB + RPV was given, followed by the first 600 mg CAB long-acting (LA) + 900 mg RPV LA intramuscular injection (IM), and second injection of CAB LA 600 mg + RPV LA 900 mg at month 2, and then subsequent injections once every 2 months (Q2M) until Month 12 (Maintenance Phase). The participants had the option to continue the regimen in the Extension Phase |
| Direct to injections (D2I) | EXPERIMENTAL | Participants with HIV-1 who chose direct to injections (D2I) received the first injections of 600 mg CAB LA + 900 mg RPV LA, IM as initial loading doses at Day 1 one month, followed by second and third subsequent injections (CAB LA 600 mg + RPV LA 900 mg) at month 1 and month 3 followed by Q2M until Month 11. The participants had the option to continue the regimen in the Extension Phase. |
| Switch Q2M Group | ACTIVE_COMPARATOR | Eligible participants with HIV-1 who received BIK tablet orally switched treatment after month 12 (Extension Phase) to CAB LA 600 mg + RPV LA 900 mg regimen, administered once every 2 months. |
| Subjects with HIV infection | EXPERIMENTAL | HIV-infected subjects receiving CAB LA+RPV LA will be included in this arm. |
| Subjects in group 1 receiving study treatment once in 4 weeks | EXPERIMENTAL | Group 1 will consist of subjects randomized from current ART SOC therapy. Subjects in group 1 will be randomized to receive CAB LA plus RPV LA Q4W via intramuscular (IM) route. All subjects will receive oral therapy with CAB 30 mg + RPV 25 mg once daily prior to randomization. |
| Subjects in group 1 receiving study treatment once in 8 weeks | EXPERIMENTAL | Group 1 will consist of subjects randomized from current ART SOC therapy. Subjects in group 1 will be randomized to receive CAB LA plus RPV LA Q8W via IM route. All subjects will receive oral therapy with CAB 30 mg + RPV 25 mg once daily prior to randomization. |
| Subjects in group 2 receiving study treatment once in 4 weeks | EXPERIMENTAL | Group 2 will consist of subjects currently receiving CAB LA + RPV LA Q4W in ATLAS study. Subjects in Group 2 will be randomized to continue CAB LA plus RPV LA Q4W administration via IM route. |
| Subjects in group 2 receiving study treatment once in 8 weeks | EXPERIMENTAL | Group 2 will consist of subjects currently receiving CAB LA + RPV LA Q4W in ATLAS study. Subjects in Group 2 will be randomized to receive CAB LA plus RPV LA Q8W via IM route. |
| CAB LA + RPV LA every 4 weeks | EXPERIMENTAL | Eligible subjects receive Oral CAB 30 mg + RPV 25 mg once daily for four weeks, IM CAB LA 600 mg and RPV LA 900 mg for the first injection, and Week 4 onwards subjects will receive CAB LA (400 mg) + RPV LA (600 mg) injections every 4 weeks until withdrawal. |
| Current antiretroviral regimen | ACTIVE_COMPARATOR | Eligible subjects will continue their current anti-retroviral regimen (2 NRTIs plus an INI, NNRTI, or a PI) for 52 weeks. After 52 weeks subjects have the option to continue study participation by switching to CAB LA + RPV LA in the Extension Phase where they will follow the procedure of CAB LA + RPV LA arm. |
| ABC / DTG / 3TC (600 mg/50mg/300mg) once daily | ACTIVE_COMPARATOR | After the Induction Phase with ABC/DTG/3TC (or DTG + two NRTIs), eligible participants will continue to receive oral ABC/DTG/3TC (or DTG + two NRTIs) initiated during the Induction Phase for 100 weeks. At the end of the Maintenance Phase, eligible participants receiving ABC/DTG/3TC (or DTG + two NRTIs) have the option to continue in the study by switching to CAB LA + RPV LA in the Extension Phase. These participants will transition to LA dosing at either Week 100 (direct to inject) or Week 104b (if using optional oral lead-in with CAB 30 mg + RPV 25 mg once daily). |
| CAB Group | EXPERIMENTAL | Participants receive lead-in injections comprising cabotegravir LA during month one and injections of a new formulation of CAB LA at Month 3, Month 5 and every 4 months thereafter to Month 29. |
| Pharmacist lead CDTM+ | OTHER | Participants will meet with a clinic-based pharmacist via telehealth for an introductory visit to discuss CAB/RPV LA and possible switch from oral to injectable therapy. The tele-visit can occur by phone or video visit. |
| CAB LA + RPV LA Q2M | EXPERIMENTAL | Eligible participants from LAI116482 (NCT01641809 \[LATTE\]) study who were administered oral CAB 30 milligrams (mg) plus RPV 25 mg and who successfully completed Week 300 received their first dose CAB LA (600 mg) plus RPV LA (900 mg) injections within 2 hours of the final oral dose of LATTE given on the same day. The second loading injections were administered 1 month after initial loading dose, with subsequent injections (CAB LA 600 mg + RPV LA 900 mg) occurring Q2M thereafter. Participants continued to receive the treatment until the study intervention was locally approved and commercially available. Participants who received at least one dose of CAB LA and/or RPV LA and discontinued the CAB LA + RPV LA regimen for any reason entered a 52-week long-term follow-up (LTFU) Phase. |
| DTG + RPV | EXPERIMENTAL | Eligible participants from LAI116482 (NCT01641809 \[LATTE\]) study who were administered oral CAB 30 mg plus RPV 25 mg and who successfully completed Week 300 received their first dose of the Dolutegravir (DTG) 50 mg plus RPV 25 mg, once daily as oral regimen on Day 1 until Month 12 in the current study. These participants were not eligible for the LTFU phase. |
| LTFU: CAB LA+RPV LA Q2M Group | EXPERIMENTAL | This group included the participants who received at least one dose of CAB LA and/or RPV LA and discontinued the CAB LA + RPV LA regimen for any reason before end of Maintenance Period. The participants entered a 52-week LTFU period. |
| CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Maintenance and Extension Period) | EXPERIMENTAL | On Day 1 of the Maintenance period, participants who successfully completed the Induction period, were randomized to receive following intramuscular (IM) doses: Day 1 only: CAB long acting (LA) 800 mg (loading dose delivered as two 400 mg IM injections) + RPV LA 900 mg IM; Week 4 only: CAB LA 600 mg IM (second loading dose, no RPV); and from Week 8: CAB LA 600 mg IM +RPV LA 900 mg IM every 8 Weeks (Q8W) for 96 weeks. Eligible participants had the option to continue study participation in the Extension Period. |
| CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Maintenance and Extension Period) | EXPERIMENTAL | On Day 1 of the Maintenance period, participants who successfully completed the Induction period, were randomized to receive following IM doses: Day 1 only: CAB LA 800 mg (loading dose delivered as two 400 mg IM injections) + RPV LA 600 mg IM; and from Week 4: CAB LA 400 mg IM + RPV LA 600 mg IM every 4 Weeks (Q4W) for 96 weeks. Eligible participants had the option to continue study participation in the Extension Period. |
| CAB 30 mg+ABC/3TC QD (Induction Period) | ACTIVE_COMPARATOR | In induction period, all participants received an oral regimen of cabotegravir (CAB) 30 milligrams (mg) once daily (QD) plus abacavir/lamivudine (ABC/3TC) 600/300 mg QD for 20 weeks. They also received an oral dose of Rilpivirine (RPV) 25 mg tablet once daily in the last 4 weeks of the Induction Period. |
| CAB 30 mg+ABC/3TC QD (Induction Period and Maintenance Period) | ACTIVE_COMPARATOR | On Day 1 of the Maintenance period, participants who successfully completed the Induction period, were randomized to receive CAB and ABC/3TC QD for 96 weeks. Eligible participants had the option to continue study participation in Extension Period by switching to an optimized IM CAB LA+ RPV LA regimen of their choice (Q8W or Q4W). |
| Optimized CAB LA 600 mg+RPV LA 900 mg IM-Q8W (Extension Period) | EXPERIMENTAL | Participants who completed 96 weeks of CAB 30 mg + ABC/3TC QD regimen in Maintenance Period transitioned to Extension Period and received an optimized loading dose of CAB LA 600 mg+RPV LA 900 mg IM at Week 100 and Week 104 followed by CAB LA 600 mg+RPV LA 900 mg IM-Q8W in the Extension Phase. Participants were followed up until end of Extension Period. |
| Optimized CAB LA 400 mg+RPV LA 600 mg IM-Q4W (Extension Period) | EXPERIMENTAL | Participants who completed 96 weeks of CAB 30 mg + ABC/3TC QD regimen in Maintenance Period transitioned to Extension Period and received an optimized loading dose of CAB LA 400 mg+RPV LA 900 mg IM at Week 100 followed by CAB LA 400 mg+RPV LA 900 mg IM-Q8W in the Extension Phase. Participants were followed up until end of Extension Period. |
| Long-Term Follow-Up Group | OTHER | This group included participants that were withdrawn from CAB LA+RPV LA IM regimens based on protocol criteria and were required to access Highly Active Antiretroviral Therapy (HAART) of choice. Participants were followed up for approximately 52 weeks. |
| Stage 1: Single Oral Dose CAB (Cohort 1) group | EXPERIMENTAL | Participants receive a single dose of oral CAB suspension on study Day 1. |
| Stage 1: Multiple Oral Dose CAB (Cohort 2) group | EXPERIMENTAL | Participants receive repeat doses of oral CAB suspension starting on study Day 1. Dose and dosing frequency to be determined based on data from Cohort 1. |
| Stage 2: Single IM Dose CAB LA (Cohort 3) group | EXPERIMENTAL | Participants receive a single IM dose of CAB LA on study Day 1. Dose to be determined based on data from Cohort 2. |
| Stage 2: Multiple IM Dose CAB LA (Cohort 4) group | EXPERIMENTAL | Participants receive repeat IM doses of CAB LA starting on study Day 1. Dose and dosing frequency to be determined based on data from Cohort 3. |
| CAB LA/LEN LA Group | EXPERIMENTAL | Participants receive the CAB LA injection at Day 1 followed by the LEN LA injections at Day 15. |
| LEN LA/CAB LA Group | EXPERIMENTAL | Participants receive the LEN LA injections at Day 1 followed by the CAB LA injection at Day 15. |
| Part A: Participants receiving CAB 200 mg/mL with rHuPH20 | EXPERIMENTAL | Part A of the study (CAB 200 mg/mL with rHuPh20) has been closed to further enrolment based on preliminary results. |
| Part C: Participants receiving CAB >=400 mg/mL or CAB Formulation I or CAB Formulation J | EXPERIMENTAL | - |
| Part E: Participants receiving RPV | EXPERIMENTAL | - |
| OLI phase followed by Injection phase | EXPERIMENTAL | Participants will be administered cabotegravir at a dose of 30 mg plus rilpivirine dose of 25 mg once daily with meal on Day 1 to Day 28 in OLI phase. There will be 10 to 14 days wash out period after OLI. This will be followed by an injection phase, wherein participants will receive 600 mg cabotegravir long acting given as one 3 milliliter (mL) IM injection plus 900 mg rilpivirine long acting given as one 3 mL IM injection on Day 1. |
| Oral Cabotegravir (CAB) 30 | EXPERIMENTAL | Participants received oral dose of CAB 30 milligram (mg) tablet once daily for Days 1 to 28 in the oral lead in phase. |
| Part 1: Cohort 1 (C1) CAB 400 | EXPERIMENTAL | Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 400 milligram per milliliter (mg/mL) (Injection 1: 600 mg and Injection 2: 400 mg respectively) intramuscularly in the gluteus medius, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase. |
| Part 1: Cohort 1 (C1) CAB200 | ACTIVE_COMPARATOR | Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 200 mg/mL (Injection 1: 600 mg and Injection 2: 400 mg respectively) intramuscularly in the gluteus medius, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase. |
| Part 1: Cohort 2 (C2) CAB400 | EXPERIMENTAL | Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 400 milligram per milliliter (mg/mL) (Injection 1: 600 mg and Injection 2: 400 mg respectively) subcutaneously in the abdomen, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase. |
| Part 1: Cohort 2 (C2) CAB200 | ACTIVE_COMPARATOR | Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 200 mg/mL (Injection 1: 300 mg and Injection 2: 200 mg respectively) subcutaneously in the abdomen, 4 weeks apart, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase. |
| Part 1: Cohort 3 (C3) CAB400 | EXPERIMENTAL | Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 400 milligram per milliliter (mg/mL) (Injection 1: 600 mg and Injection 2: 400 mg respectively) intramuscularly in the lateral thigh, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase. |
| Part 1: Cohort 3 (C3) CAB200 | ACTIVE_COMPARATOR | Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 200 mg/mL (Injection 1: 600 mg and Injection 2: 400 mg respectively) intramuscularly in the lateral thigh, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase. |
| Part 1: Cohort 4 (C4) CAB400 | EXPERIMENTAL | Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB400 mg/mL (Injection 1: 400 mg and Injection 2: 200 mg respectively) at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase, with the first injection in the gluteus medius intramuscularly and the second subcutaneously. |
| Part 1: Cohort 4 (C4) CAB200 | ACTIVE_COMPARATOR | Following receipt of oral CAB 30 in the OLI phase, participants received two injections of CAB 200 mg/mL (Injection 1: 400 mg and Injection 2: 100 mg respectively) at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase, with the first injection in the gluteus medius intramuscularly and the second subcutaneously. |
| Part 1: Cohort 4b Group 1 (C4b G1) | EXPERIMENTAL | Following receipt of oral CAB 30 in the OLI phase, all participants received two injections of 300 mg of CAB 400 mg/mL subcutaneously, at Day 1 of Injection Phase and approximately at Week 4 of Injection Phase, The participants received a topical non-steroidal anti-inflammatory drug (NSAID) and topical steroid placebo with Injection 1, a topical steroid and NSAID placebo with Injection 2. |
| Part 1: Cohort 4b Group 2 (C4b G2) | EXPERIMENTAL | Following receipt of oral CAB 30 in the OLI phase, all participants received two injections of 300 mg of CAB 400 mg/mL subcutaneously 4 weeks apart. The participants received a topical steroid and NSAID placebo with injection 1, NSAID and topical steroid placebo with injection 2. |
| Part 1: Cohort 4h (C4h) CAB400 + rHuPH20 | EXPERIMENTAL | Following receipt of oral CAB 30 in the OLI phase, participants received one subcutaneous injection of 400 mg of CAB 400 mg/mL along with 5000 units (U) of recombinant human hyaluronidase PH20 (rHuPH20) sequentially. |
| Part 1: Cohort 4h (C4h) CAB200 + rHuPH20 | EXPERIMENTAL | Following receipt of oral CAB 30 in the OLI phase, participants received one subcutaneous injection of 400 mg of CAB 200 mg/mL along with 5000 U of rHuPH20 sequentially. |
| Part 2: Cohort 5 (C5) CAB400 | EXPERIMENTAL | Following receipt of oral CAB 30 in the OLI phase, participants received two intramuscular gluteal injections of 800 mg of CAB 400 mg/mL approximately 12 weeks apart. |
| Part 2: Cohort 5 (C5) CAB200 | ACTIVE_COMPARATOR | Following receipt of oral CAB 30 in the OLI phase, participants received two intramuscular gluteal injections of 400 mg of CAB 200 mg/mL approximately 12 weeks apart. The dose was matched to the volume of CAB 400 mg/mL administered earlier in the same cohort. |
| Subjects receiving CAB | EXPERIMENTAL | Eligible subjects will receive oral doses of CAB 30 milligrams (mg) tablets once daily for 4 weeks followed by IM injectable suspension of CAB LA 600 mg at Week 5, Week 9, Week 17, Week 25 and Week 33. There will be an approximately 1-week washout period between the last oral dose and the first injection of CAB at Week 5. |
| Treatment A | EXPERIMENTAL | Participants will be administered a single oral dose of CAB 30 mg after an overnight fast of at least 6 hours for 14 days in Period 1. Dosing of study medication on non-PK days may be with or without food. |
| Treatment B | EXPERIMENTAL | Participants will be administered a single dose of RBT 300 mg and a single dose of CAB 30 mg after an overnight fast of at least 6 hours once daily for 14 days in Period 2. Dosing of study medication on non-PK days may be with or without food. |
| Cabotegravir 30 mg: Sequence AB (fasted followed by fed) | EXPERIMENTAL | There will be two administration periods with 14 days of wash out. In Period 1, eligible subjects will receive a single tablet of cabotegravir 30 mg,(micronized 500 mg core weight) orally under fasted condition with at least 10 hours of prior fast. In Period 2, eligible subjects will receive single tablet of cabotegravir 30 mg, micronized 500 mg core weight orally following a high fat meal. Blood samples will be withdrawn from subjects prior to dosing and upto 8 days after the last dose of cabotegravir. |
| Cabotegravir 30 mg: Sequence BA (fed followed by fasted) | EXPERIMENTAL | There will be two administration periods with 14 days of wash out. In Period 1, eligible subjects will receive single tablet of cabotegravir 30 mg, micronized 500 mg core weight orally following a high fat meal. In Period 2, eligible subjects will receive a single tablet of cabotegravir 30 mg, micronized 500 mg core weight orally under fasted condition with at least 10 hours of prior fast. Blood samples will be withdrawn from subjects prior to dosing and upto 8 days after the last dose of cabotegravir. |
| Treatment A(CAB 30mg)+B (RIF 600mg)+C (CAB 30mg and RIF 600mg) | EXPERIMENTAL | Subjects will receive a single dose of CAB 30 mg on day 1. Subjects will then receive RIF 600 mg once daily on days 8-28 with co-administration of a single dose of CAB 30 mg on day 21. |
| Part A | EXPERIMENTAL | Subjects will receive reference cabotegravir 30 mg current formulation (Treatment A), Cabotegravir 30 mg micronized new formulation 500 M (Treatment B) and Cabotegravir 30 mg unmicronized new formulation 500 U (Treatment C) in one of six sequences ABC, ACB, BCA, BAC, CAB, CBA in three treatment periods under fasting condition |
| Part B | EXPERIMENTAL | Subjects will receive reference Cabotegravir 30 mg current formulation (Treatment A), Cabotegravir 30 mg micronized new formulation 650 M (Treatment D) and Cabotegravir 30 mg unmicronized new formulation 650 U (Treatment E) in one of six sequences ADE, AED, DAE, DEA, EAD, EDA in three treatment periods under fasting condition |
| Name | Type | Description |
|---|---|---|
| CAB ULA | DRUG | CAB ULA will be administered. |
| RPV ULA | DRUG | RPV ULA will be administered. |
| CAB LA | DRUG | CAB LA will be administered. |
| RPV LA | DRUG | RPV LA will be administered. |
| CAB LA + RPV LA | DRUG | Intramuscular injection administered monthly for first 2 initiation doses then every 2 months. |
| Oral ART | DRUG | Oral medication provided to participants by the site/their regular healthcare professional (HCP) as part of their standard of care (SOC) treatment. |
| Cabotegravir - Injectable Suspension (CAB LA) | DRUG | It is a sterile white to slightly pink suspension containing 200 mg/mL of CAB as free acid for administration by intramuscular (IM) injection. Each vial is for single-dose use containing a withdrawable volume of 2.0 mL, and does not require dilution prior to administration. CAB LA is composed of cabotegravir free acid, polysorbate 20, polyethylene glycol 3350, mannitol, and water for injection. |
| Rilpivirine - Injectable Suspension (RPV LA) | DRUG | It is a sterile white suspension containing 300 mg/mL of RPV as the free base. The route of administration is by intramuscular (IM) injection. Each vial contains a nominal fill of 2.0 mL, and does not require dilution prior to administration. RPV LA requires refrigeration and must be protected from light. RPV LA is composed of RPV free base, poloxamer 338, sodium dihydrogen phosphate monohydrate, citric acid monohydrate, glucose monohydrate, sodium hydroxide, water for injection. |
| Cabotegravir Injectable Suspension | DRUG | CAB LA injectable suspension is a sterile white to slightly pink suspension containing 200 milligrams per milliliter (mg/mL) of GSK1265744 as free acid for administration by IM injection. CAB LA injectable suspension is to be stored at up to 30 degree Celsius and should not be frozen. |
| Rilpivirine Injectable Suspension | DRUG | RPV LA injectable suspension is a sterile white suspension containing 300 mg/mL of RPV as the free base for administration by IM injection. RPV LA injectable suspension should be kept in the outer package and stored at 2-8 degree Celsius and should not be frozen. RPV LA should also be protected from light. |
| Cabotegravir Tablets | DRUG | CAB tablets were available as film coated tablets for oral administration. |
| Cabotegravir Injectable Suspension (CAB LA) | DRUG | CAB LA was available as sterile suspension for injection in GSK1265744 for administration as IM injection. |
| Rilpivirine Tablets | DRUG | RPV was administered as tablets for oral administration. |
| Rilpivirine Injectable Suspension (RPV LA) | DRUG | RPV LA was available as a sterile suspension of RPV to be administered as an IM injection. |
| BIKTARVY Tablets (BIK) | DRUG | BIK was a three-drug fixed dose combination product BIC, FTC, and TAF for oral administration. |
| CAB LA+RPV LA | DRUG | Subjects will receive one tablet of CAB 30 milligram(mg) + RPV 25 mg once daily from Day 1 for 1 month. During month 1, subjects will receive 600 mg of CAB LA injection+ 900 mg of RPV LA injection. Following Month 1, subjects will receive 400mg of CAB LA + 600mg of RPV LA at each subsequent injection. |
| Cabotegravir (CAB) tablet | DRUG | It is a white oval shaped film coated 30 mg tablets for oral administration. CAB Tablet is composed of cabotegravir sodium, lactose monohydrate, microcrystalline cellulose, hypromellose, sodium starch glycolate, magnesium stearate, and white film-coat |
| Rilpivirine (RPV) tablet | DRUG | It is a 25 mg tablet with off-white, round, biconvex, film-coated and debossed on one side with "TMC" and the other side with "25". Each tablet contains RPV hydrochloride, and the inactive ingredients croscarmellose sodium, lactose monohydrate, magnesium stearate, polysorbate 20, povidone K30 and silicified microcrystalline cellulose |
| 2 NRTIs plus an INI, NNRTI, or PI | DRUG | Acceptable stable (initial or second) ARV regimens include 2 NRTIs plus: * INI with the exception of ABC/DTG/3TC (either the initial or second cART regimen) * NNRTI (either the initial or second cART regimen) * Boosted PI (or atazanavir \[ATV\] unboosted) (either the initial or second PI-based cART regimen) |
| ABC/DTG/3TC STR - Tablet | DRUG | It is a purple, biconvex, oval, tablet debossed with "572 Tri" on one side, film-coated tablet contains abacavir sulphate equivalent to 600 mg of abacavir, dolutegravir sodium equivalent to 50 mg dolutegravir, and 300 mg of lamivudine. The inactive ABC/DTG/3TC tablet ingredients include D-mannitol, magnesium stearate, microcrystalline cellulose, povidone, and sodium starch glycolate. |
| DTG Tablet | DRUG | It is a yellow, round, biconvex, 50 mg film-coated tablet debossed with "SV 572" on one side and "50" on the other side. Each tablet of DTG also contains the following inactive ingredients: D-mannitol, microcrystalline cellulose, povidone K29/32, sodium starch glycolate, and sodium stearyl fumarate. |
| New formulation of CAB LA | DRUG | Injections administered IM gluteal. |
| Collaborative drug therapy management model | BEHAVIORAL | CDTM+ is an interdisciplinary approach to patient care in which clinicians collaborate with pharmacists to provide and manage patient drug therapy. |
| Cabotegravir/Rilpivirine | DRUG | Long-acting injectable treatment prescribed to treat HIV-1 infection in people 12 years and older and who weigh at least 77 lbs (35kg), to replace their current HIV-1 medicines when their healthcare provider determines they meet certain requirements. |
| RPV | DRUG | Oral dose of RPV 25 mg, administered once daily from Day 1 up to Month 12 |
| DTG | DRUG | Oral dose of DTG 50 mg administered once daily from Day 1 up to Month 12. |
| CAB Oral Tablets | DRUG | White to almost white oval shaped film coated 30 mg tablets for oral administration. |
| ABC/3TC Oral tablets | DRUG | ABC/3TC fixed dose combination (FDC) oral tablet, containing 600 mg of ABC (as abacavir sulfate) and 300 mg of 3TC |
| RPV Oral Tablets | DRUG | Off-white, round, biconvex, film-coated 25 mg Rilpivirine (RPV) tablets for oral administration. Eligible subjects switching from the oral regimen to the IM regimen in the Extension Period will receive 2 weeks of RPV 25 mg once daily, from Week 102 through Week 104 |
| HAART | OTHER | Higly-active antiretroviral therapy chosen by participant based on investigator recommendations and based on availability. |
| Oral CAB | DRUG | CAB administered once orally on study Day 1 to the Stage 1: Single Oral Dose CAB (Cohort 1) and multiple times to the Stage 1: Multiple Oral Dose CAB (Cohort 2) group. Dose and dosing frequency for Cohort 2 to be determined based on emerging data from Cohort 1. |
| IM CAB LA | DRUG | CAB LA administered once intramuscularly on study Day 1 to the Stage 2: Single IM Dose CAB LA (Cohort 3) group and multiple times to the Stage 2: Multiple IM Dose CAB LA (Cohort 4) group, into the in the anterolateral thigh muscle of participants. Dose for Cohort 3 to be determined based on emerging data from Cohort 2. Dose and dosing frequency for Cohort 4 to be determined based on emerging data from Cohort 3. |
| Cabotegravir long-acting | DRUG | A single CAB LA injection administered intramuscularly. |
| Lenacapavir long-acting | DRUG | Two LEN LA injections administered subcutaneously. |
| Cabotegravir 200 mg/mL | DRUG | CAB 200 mg/mL will be administered. |
| Cabotegravir >=400 mg/mL | DRUG | CAB \>=400 mg/mL will be administered by IM or SC injection. |
| Cabotegravir Formulation I | DRUG | CAB Formulation I will be administered by IM injection. |
| CAB Formulation J | DRUG | CAB Formulation J will be administered by IM injection. |
| rHuPH20 | DRUG | rHuPH20 will be administered. |
| Cabotegravir extended release suspension for injection (long-acting) | DRUG | Cabotegravir long-acting will be a sterile white to slightly pink suspension containing 200 mg per mL of GSK1265744 as free acid for administration by intramuscular injection. |
| Rilpivirine extended release suspension for injection (long-acting) | DRUG | Rilpivirine long-acting will be a sterile white suspension containing 300 mg per mL of rilpivirine as the free base for administration by intramuscular injection. |
| Cabotegravir sodium (Oral Lead In) | DRUG | CAB 30 mg tablets administered orally. |
| Cabotegravir 400 mg/mL | DRUG | CAB 400 mg/mL administered intramascularly or subcutaneously. |
| Topical Non-steroidal anti-inflammatory drug (NSAID) | DRUG | NSAID applied topically. |
| Topical steroid | DRUG | Steroid medication applied topically. |
| Topical NSAID placebo | DRUG | Placebo for NSAID applied topically. |
| Recombinant human hyaluronidase PH20 (rHuPH20) | DRUG | rHuPH20 administered subcutaneously. |
| Topical steroid placebo | DRUG | Placebo for steroid applied topically. |
| Cabotegravir | DRUG | It will be available as a white aquarius film coated tablet for oral administration. CAB Tablet is composed of GSK1265744B (micronized) lactose monohydrate, microcrystalline cellulose, hypromellose, sodium starch glycolate, magnesium stearate |
| Rifabutin | DRUG | It will be available as an opaque red-brown hard gelatin capsules containing 150 mg of rifabutin for oral administration. These capsules are composed of rifabutin, microcrystalline cellulose, sodium lauryl sulphate, magnesium stearate, and silica gel |
| Cabotegravir 30 mg | DRUG | Cabotegravir (GSK1265744B ) is available as white to almost white, oval shaped, film coated tablet, of weight 515 mg. The tablet contains micronized cabotegravir, lactose monohydrate, microcrystalline cellulose, hypromellose, sodium starch glycolate, and magnesium stearate. Each tablet is equivalent to 30 mg cabotegravir and needs to be taken orally with 240 mL of water. Cabotegravir tablet will be administered to subjects either in fasting condition or following a high fat meal. |
| CAB | DRUG | CAB 30 mg as 1 tablet will be administered orally with 240 mL of water in the fasted state. |
| RIF | DRUG | RIF 600 mg as 2 capsules of 300 mg will be administered orally with 240 mL of water in the fasted state. |
| Cabotegravir 30 mg current formulation | DRUG | Cabotegravir 30 mg current formulation (Treatment A) is a film coated tablet with a weight of 824 mg |
| Cabotegravir 30 mg micronized new formulation 500 M | DRUG | Cabotegravir 30 mg micronized new formulation 500 M (Treatment B) is a film coated tablet with a weight of 515 mg |
| Cabotegravir 30 mg unmicronized new formulation 500 U | DRUG | Cabotegravir 30 mg unmicronized new formulation 500 U (Treatment C) is a film coated tablet with a weight of 515 mg |
| Cabotegravir 30 mg micronized new formulation 650 M | DRUG | Cabotegravir 30 mg micronized new formulation 650 M (Treatment D) is a film coated tablet with a weight of 670 mg |
| Cabotegravir 30 mg unmicronized new formulation 650 U | DRUG | Cabotegravir 30 mg unmicronized new formulation 650 U (Treatment E) is a film coated tablet with a weight of 670 mg |
Inclusion criteria: Patient Study Participant (PSP) Inclusion criteria: * Adults and adolescents with HIV-1 infection aged 12 years or older with a weight \>35 kg. * Documented HIV-1 RNA measurements \<50 copies/mL in the 12 months prior to Screening. * HIV-1 RNA \<50 copies/mL at screening assess...
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Cabotegravir is an investigational small molecule developed by GSK plc for the treatment and prevention of HIV infections, including HIV-1. It is studied in oral tablet and long-acting injectable suspension formulations, and is also being evaluated in combination with rilpivirine long-acting (RPV LA).
Cabotegravir is being developed for HIV infections, including human immunodeficiency virus type 1 (HIV-1). Clinical trials are evaluating it in adults and adolescents who are virologically suppressed, in neonates exposed to HIV-1, and in healthy adults without HIV for tolerability and acceptability.
Cabotegravir is developed by GSK plc, which trades under the ticker GSK. GSK is the sponsor of the clinical trials evaluating cabotegravir in HIV infections.
Cabotegravir is in Phase 3 clinical development. It is investigational and has not been approved by the FDA for any indication. The Phase 3 program includes a recruiting trial of cabotegravir ultra long-acting plus rilpivirine ultra long-acting in virologically suppressed adults and adolescents with HIV.
Cabotegravir is being studied in 16 clinical trials, with 10 active and 6 completed, enrolling 7,287 participants overall. Active trials include NCT07650916 (Phase 3, cabotegravir ultra long-acting plus rilpivirine ultra long-acting), NCT07275606 (Phase 1, neonates exposed to HIV-1), NCT06970223 (Phase 1, tolerability with lenacapavir), and NCT06786520 (Phase 1, switch from cabotegravir long-acting to ultra long-acting).
Yes, cabotegravir is known by several alternative names including CAB LA (cabotegravir long-acting), CAB ULA (cabotegravir ultra long-acting), oral CAB, and cabotegravir injectable suspension. CAB LA + RPV LA refers to the combination of cabotegravir long-acting with rilpivirine long-acting. These names refer to the same drug in different formulations or combinations.