Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Oral CAB
CAB · 4 trials · 2 indications
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.
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.
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.
| Arm | Type | Description |
|---|---|---|
| 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. |
| 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(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. |
| Name | Type | Description |
|---|---|---|
| CAB Oral Tablets | DRUG | White to almost white oval shaped film coated 30 mg tablets for oral administration. |
| CAB LA | DRUG | Sterile white to slightly colored suspension containing 200 mg/mL of GSK744 as free acid (GSK1265744 free acid), polysorbate 20, polyethylene glycol 3350, mannitol, and water for injection, packaged in a 3 mL USP Type I glass vial, for administration by IM injection |
| 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. |
| RPV | DRUG | Sterile white suspension containing 300 mg/mL of TMC278 as free base, poloxamer 338, sodium dihydrogen phosphate monohydrate, citric acid monohydrate, glucose monohydrate, sodium hydroxide, water for injection, packaged in a 2 mL USP Type I glass vial, for administration by IM injection. |
| 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. |
| 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. |
Inclusion Criteria: * Subjects screened for this study must be HIV-1 infected and \>=18 years of age. * A female subject is eligible to enter and participate in the study if she: is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and \>=45 years...
CAB, also known as Oral CAB, is an investigational small molecule being developed for the treatment and prevention of HIV infections, including Human Immunodeficiency Virus type 1. It is currently in Phase 1 clinical development, with studies evaluating its safety, tolerability, and pharmacokinetics in various populations, including healthy volunteers and HIV-exposed neonates.
CAB is a small molecule designed to target HIV infection. As an integrase inhibitor, it works by blocking the integration of viral DNA into the host cell genome, thereby preventing viral replication. This mechanism is being studied in clinical trials for both treatment and prevention of HIV-1 infection.
CAB is being developed by GSK plc, a global biopharmaceutical company. The company is conducting clinical trials to evaluate the drug's safety and efficacy for HIV infections. GSK's ticker symbol is GSK, and they are responsible for the ongoing research and development of this investigational therapy.
CAB is currently in Phase 1 clinical development. While some completed trials have been conducted, the drug remains investigational and is not yet approved by regulatory authorities. The ongoing Phase 1 study is recruiting participants to further evaluate its safety and pharmacokinetics in specific populations.
CAB has been studied in several clinical trials, including NCT02120352, a Phase IIb study of a long-acting regimen, and NCT02411435, a Phase 1 drug interaction study. Currently, NCT07275606 is recruiting to investigate CAB for neonates exposed to HIV-1, with a total enrollment of 44 participants.
Yes, CAB is also known as Oral CAB. This alternative name is used in clinical research to distinguish the oral formulation from other potential routes of administration. Both names refer to the same investigational drug being developed by GSK for HIV infections.