Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication SELZENTRY is indicated in combination with other antiretroviral agents for the treatment of only CCR5‑tropic human immunodeficiency virus type 1 (HIV‑1) infection in adult and pediatric patients weighing at least 2 kg. Limitations of Use • SELZENTRY is not recommended in patients with dual/mixed- or CXCR4-tropic HIV-1 [see Microbiology ( 12.4 )]. FDA label
Maraviroc · 11 trials · 9 indications
AEs: any untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was congenital anomaly. Grade 3: Events that interrupted participant's usual daily activity and traditionally required systemic drug therapy or other treatment. Grade 4: Events which were unacceptable and intolerable or which were irreversible or caused participant to be in imminent danger of death.
Grade 3 or severe events included those that interrupted participant's usual daily activity and traditionally required systemic drug therapy or other treatment. Grade 4 or very severe events included those that were unacceptable and intolerable or which were irreversible or caused the participant to be in imminent danger of death.
Number of participants with AIDS-related infections based on investigator classification guided by a predefined list of clinical Category C AEs per Center for Disease Control (CDC) HIV Classification System.
Pre-defined criteria based on upper limit normal (ULN) and lower limit normal (LLN) were established for each laboratory test to define the values that would be identified as laboratory test abnormality.
AEs as defined by the Division of AIDS (DAIDS) toxicity grading scale: Grade 3 = severe: interrupted usual daily activity and traditionally required systemic drug therapy or other treatment. Grade 4 = very severe: events that were unacceptable and intolerable or were irreversable or caused imminent danger of death. If same participant had more than 1 occurrence in the same preferred term event category, only the most severe (grade 4) occurrence was taken. Treatment-related = investigator assessment of a reasonable possibility that the investigational product caused or contributed to the AE.
Laboratory abnormalities as defined by the Division of AIDS (DAIDS) toxicity grading scale: Grade 3, Severe =events that interrupted participants usual daily activity and traditionally required systemic drug therapy or other treatment.
Laboratory abnormalities as defined by the Division of AIDS (DAIDS) toxicity grading scale: Grade 4, Very Severe = events which were unacceptable and intolerable or were irreversible or caused the participant to be in imminent danger of death.
Treatment-emergent AIDS-defining opportunistic illnesses based on investigator classification guided by a predefined list of clinical Category C adverse events per Center for Disease Control (CDC) HIV Classification System. Includes events occurring up to 30 days after last dose of study drug.
Treatment-emergent AEs by gender that occurred up to 30 days after the last dose of study medication.
Treatment-emergent AEs by race that occurred up to 30 days after the last dose of study medication.
Treatment-emergent AEs by age that occurred up to 30 days after the last dose of study medication.
Treatment emergent AEs by hepatis B and hepatitis C serology status that occurred up to 30 days post last dose.
Percentage of participants with viral load of less than 400 copies/mL and less than 50 copies/mL of HIV-1 RNA were not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.
Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.
Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.
Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.
To assess the safety and tolerability of single and repeat inhaled doses of GSK2339345 administered by an aqueous droplet inhaler
To assess the changes in oropharyngeal sensation caused by single and repeat inhaled doses of GSK2339345 administered by an aqueous droplet inhaler
| Arm | Type | Description |
|---|---|---|
| 1 | EXPERIMENTAL | - |
| 3 | ACTIVE_COMPARATOR | - |
| 2 | EXPERIMENTAL | Following a review of the interim analysis data, the DSMB recommended to terminate the UK-427,857 300 mg QD arm based on pre-specified protocol non-inferiority criteria not being met for the QD arm versus efavirenz |
| Arm A | EXPERIMENTAL | maraviroc (Selzentry, Celsentri) 150 mg QD + atazanavir (Reyataz) /ritonavir (Norvir) 300/100mg QD Subjects experiencing unconjugated hyperbilirubinemia attributable to atazanavir (Reyataz) /ritonavir (Norvir) without any other etiology of hyperbilirubinemia, responding to the therapy without virologic failure, but expressing cosmetic concerns because of the jaundice or scleral icterus (associated with bilirubin elevations) and wish to discontinue atazanavir (Reyataz) in spite of reassurances by the investigator, will be permitted on a single occasion only to switch to another protease inhibitor either darunavir (Prezista)/ritonavir (Norvir)((800/100 mg) QD or lopinavir/ritonavir (Kaletra, Aluvia)(400/100mg) BID and remain in the study. If the investigator decides to switch to a protease inhibitor other than darunavir (Prezista)/ritonavir (Norvir) or lopinavir/ritonavir (Kaletra, Aluvia)(, then the subject must be discontinued from the study. |
| Arm B | EXPERIMENTAL | emtricitabine/tenofovir (Truvada) 200/300mg QD + atazanavir (Reyataz) /ritonavir (Norvir) 300/100 mg QD Subjects experiencing unconjugated hyperbilirubinemia attributable to atazanavir (Reyataz) /ritonavir (Norvir) without any other etiology of hyperbilirubinemia, responding to the therapy without virologic failure, but expressing cosmetic concerns because of the jaundice or scleral icterus (associated with bilirubin elevations) and wish to discontinue atazanavir in spite of reassurances by the investigator, will be permitted on a single occasion only to switch to another protease inhibitor either darunavir/ritonavir (800/100 mg) QD or lopinavir/ritonavir (400/100mg) BID and remain in the study. If the investigator decides to switch to a protease inhibitor other than darunavir/ritonavir or lopinavir/ritonavir, then the subject must be discontinued from the study. |
| 4 | EXPERIMENTAL | - |
| 5 | PLACEBO_COMPARATOR | - |
| A | EXPERIMENTAL | - |
| B | EXPERIMENTAL | - |
| C | EXPERIMENTAL | - |
| D | EXPERIMENTAL | - |
| E | PLACEBO_COMPARATOR | - |
| Sequence 1 | EXPERIMENTAL | Treatment A: 1 tablet of GSK2838510 (maraviroc 300 mg, lamivudine 150 mg, and zidovudine 300 mg as a combined formulation) after an overnight fast Washout Treatment B: 1 tablet of maraviroc 300 mg + 1 tablet of Combivir taken concurrently after an overnight fast. |
| Sequence 2 | EXPERIMENTAL | Treatment B: 1 tablet of maraviroc 300 mg + 1 tablet of Combivir taken concurrently after an overnight fast. Washout Treatment A: 1 tablet of GSK2838510 (maraviroc 300 mg, lamivudine 150 mg, and zidovudine 300 mg as a combined formulation) after an overnight fast |
| Digoxin | ACTIVE_COMPARATOR | - |
| Digoxin + Maraviroc | EXPERIMENTAL | - |
| Active group | OTHER | maraviroc dosing group |
| Name | Type | Description |
|---|---|---|
| Maraviroc | DRUG | Maraviroc should be dosed BID with total dose adjusted according to the other drugs the patient is taking. Maraviroc may be taken with or without food. The subject should only take missed doses if it is not within 6 hours prior to the planned next dose. No dose adjustment of OBT is required due to the presence of maraviroc. |
| Maraviroc + Zidovudine/Lamivudine | DRUG | maraviroc (UK-427,857) 300 mg once daily added to zidovudine/lamivudine (300 mg/150 mg twice daily) |
| Efavirenz + Zidovudine/Lamivudine | DRUG | efavirenz (600 mg once daily) added to zidovudine/lamivudine (300 mg/150 mg twice daily) |
| Maraviroc (UK-427,857) + Zidovudine/Lamivudine | DRUG | maraviroc (UK-427,857) 300 mg twice daily added to zidovudine/lamivudine (300 mg/150 mg twice daily) |
| Maraviroc (UK-427,857) | DRUG | maraviroc (UK-427,857) 150 mg taken once daily, OBT + maraviroc (UK-427,857) 150 mg taken twice daily, or OBT alone. |
| optimized background therapy | DRUG | \[OBT (3-6 drugs based on treatment history and resistance testing)\] |
| Placebo | DRUG | Patients will be randomly (2:2:1) assigned to one of three groups: Optimized Background Therapy \[OBT (3-6 drugs based on treatment history and resistance testing)\] + maraviroc (UK-427,857) 150 mg taken once daily, OBT + maraviroc (UK-427,857) 150 mg taken twice daily, or OBT alone. |
| Combivir | DRUG | 1 tablet: lamivudine 150mg, zidovudine 300mg |
| GSK2838510 | DRUG | Maraviroc 300mg, lamivudine 150mg, zidovudine 300mg |
| Digoxin | DRUG | Oral Digoxin 0.25 mg single dose |
| maraviroc (Selzentry, Celsentri) | DRUG | 12 subjects will receive a single dose of 300 mg maraviroc (two 150 mg maraviroc commercial tablets) under fasting conditions. |
Inclusion Criteria: * Subjects with limited or no approved treatment options available to them due to resistance or intolerance; * Subjects must be failing to achieve adequate virologic suppression on their current regimen and have HIV-1 RNA ≥ 1000 copies/ml, at screening. * Have only R5 HIV-1 at S...
Maraviroc is used to treat HIV-1 infection and HIV infections, including acquired immunodeficiency syndrome. It is a small molecule CCR5 antagonist developed by GSK plc under the ticker GSK. The drug is in Phase 3 clinical development for these infectious disease indications.
Maraviroc targets CCR5, a chemokine receptor on the surface of certain immune cells. It acts as a CCR5 antagonist, blocking the receptor to prevent HIV-1 from entering host cells. This mechanism is specific to CCR5-tropic virus and is the basis for its use in HIV treatment.
Maraviroc is developed by GSK plc, which trades under the ticker GSK. GSK is the company responsible for the clinical development of maraviroc, including the trials listed for HIV and related conditions.
Maraviroc is in Phase 3 clinical development. It is an investigational drug for HIV and related infections, and it has not been approved by the FDA for these uses. The development program includes completed Phase 1 and Phase 2 trials, with Phase 3 status overall.
Maraviroc has been studied in completed clinical trials including NCT01597648, a Phase 1 bioequivalence study; NCT01056874, a Phase 1 drug interaction study; NCT00827112, a Phase 2 pilot study in treatment-naive HIV patients; and NCT00821535, a Phase 1 pharmacokinetic study in healthy Japanese volunteers.
Yes, maraviroc is also known by the brand names Selzentry and Celsentri. It is additionally referred to as UK-427,857 and has been studied in combination with zidovudine and lamivudine. These alternative names all refer to the same CCR5 antagonist developed by GSK.