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Maraviroc

Phase 3

Acquired Immunodeficiency Syndrome | Small molecule | Infectious Disease |GSK plc|Last Updated: Apr 17, 2017

Success Probability

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Market & Valuation

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Trial Design

UNCONTROLLED
Total Trials1
Total Enrollment209

FDA Designations

No designations recorded

Clinical trial landscape

Maraviroc · 14 trials · 9 indications

Phase 3 2Phase 2 6Phase 1 6
NCT00478231Multicenter, Safety Study Of MaravirocAcquired Immunodeficiency Syndrome
COMPLETED209 Analytics
NCT00426660Expanded Access Program for Maraviroc At Multiple CentersHIV Infections
COMPLETED1,047 Analytics
PHASE3COMPLETED
Multicenter, Safety Study Of Maraviroc
Acquired Immunodeficiency SyndromeUnlock trial analytics
PHASE3COMPLETED
Expanded Access Program for Maraviroc At Multiple Centers
HIV InfectionsUnlock trial analytics

Study Endpoints

Primary Endpoints

Number of Participants With Grade 3 and Grade 4 Adverse Events (AEs) and Serious Adverse Events (SAEs)
Baseline to 30 days post-week 96 or early termination (ET)

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.

Number of Participants With Division of Acquired Immunodeficiency Syndrome (DAIDS) Grade 3 and Grade 4 Laboratory Abnormalities
Baseline to 30 days post-week 96 or ET

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 Treatment Emergent Malignancies
Baseline to 30 days post-week 96 or ET
Number of Participants With Category C Acquired Immunodeficiency Syndrome (AIDS) Related Infections
Baseline to 30 days post-week 96 or ET

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.

Number of Participants With Laboratory Test Abnormalities
Baseline to 30 days post-week 96 or ET

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.

Percentage of Participants With Grade 3 and Grade 4 Adverse Events (AE)
Baseline up to Week 144

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.

Percentage of Participants With Grade 3 Laboratory Abnormalities Without Regards to Baseline Abnormalities
Baseline up to Week 144

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.

Percentage of Participants With Grade 4 Laboratory Abnormalities Without Regards to Baseline Abnormalities
Baseline up to Week 144

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.

Percentage of Participants With Acquired Immunodeficiency Syndrome (AIDS)-Defining Illnesses
Baseline up to Week 144

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.

Percentage of Participants With Possible Acquired Immunodeficiency Syndrome (AIDS) Related Infections and Malignancies by Baseline Viral Load
Baseline up to Week 144
Percentage of Participants With Possible Acquired Immunodeficiency Syndrome (AIDS) Related Infections and Malignancies by Baseline/Nadir CD4 Cell Counts
Baseline up to Week 144
Percentage of Participants With Possible Acquired Immunodeficiency Syndrome (AIDS) Related Infections and Malignancies by Time on Therapy
Baseline up to Week 144
Percentage of Participants With All Causality Treatment-emergent Adverse (AEs) Events by Gender
Baseline up to Week 144

Treatment-emergent AEs by gender that occurred up to 30 days after the last dose of study medication.

Percentage of Participants With Treatment-emergent Adverse Events (AEs) by Race
Baseline up to Week 144

Treatment-emergent AEs by race that occurred up to 30 days after the last dose of study medication.

Percentage of Participants With Treatment-emergent Adverse Events (AEs) by Age
Baseline up to Week 144

Treatment-emergent AEs by age that occurred up to 30 days after the last dose of study medication.

Percentage of Participants With Treatment-emergent Averse Events (AEs) by Baseline Hepatitis B and Hepatitis C Virus Serology Status
Baseline up to Week 144

Treatment emergent AEs by hepatis B and hepatitis C serology status that occurred up to 30 days post last dose.

Cmin/Cmax: Steady-state Plasma Amprenavir (APV) Pharmacokinetics ( PK) Following Admin of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent (Maraviroc) MVC 300mg BID.
Day 14 of the FPV 1400mg BID, FPV 1400mg/MVC 300mg BID, FPV 700mg/RTV 100mg BID, FPV 700mg/RTV 100mg/MVC 300mg BID, FPV 1400mg/RTV 100mg QD, and FPV 1400mg/RTV 100mg QD plus MVC 300mg BID regimens

Amprenavir (APV) is the active ingredient/metabolite of Fosamprenavir (FPV).

AUC: Steady-state Plasma Amprenavir (APV) Pharmacokinetics ( PK) Following Admin of Fosamprenavir (FPV) 1400mg BID, FPV 700mg/Ritonavir (RTV) 100 mg BID, or FPV 1400mg/RTV 100mg QD With and Without Concurrent (Maraviroc) MVC 300mg BID.
Day 14 of the FPV 1400mg BID, FPV 1400mg/MVC 300mg BID, FPV 700mg/RTV 100mg BID, FPV 700mg/RTV 100mg/MVC 300mg BID, FPV 1400mg/RTV 100mg QD, and FPV 1400mg/RTV 100mg QD plus MVC 300mg BID regimens

Amprenavir (APV) is the active ingredient/metabolite of Fosamprenavir (FPV).

Cmin/Cmax: Steady-state Plasma MVC PK Following Administration of RTV
Day 7 of the MVC 300mg BID regimen and Day 14 of the MVC 300mg/FPV 1400mg BID, MVC 300mg/FPV 700mg/RTV 100mg BID, and MVC 300mg BID Plus FPV 1400mg/RTV 100mg QD regimens

Amprenavir (APV) is the active ingredient/ metabolite of Fosamprenavir (FPV). MVC minimum concentration (Cmin), maximum concentration (Cmax), and area under the plasma concentration-time curve (AUC), as determined from MVC concentrations observed in blood samples obtained at baseline, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours during the period when MVC 300mg BID was administered with the FPV-Containing BID regimens (FPV 1400mg BID, FPV 700mg/RTV 100 mg BID), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours during the period when MVC 300mg BID was administered with the FPV QD regimen (FPV 1400mg/RTV 100mg QD). As Groups A and B received the same regimens (albeit in different order), PK data for these two groups were collated, then assessed. For the same reason, PK data from Groups C and D regimens were collated before assessment, as were the PK data from Groups E and F.

AUC: Steady-state Plasma MVC PK Following Administration of RTV
Day 7 of the MVC 300mg BID regimen and Day 14 of the MVC 300mg/FPV 1400mg BID, MVC 300mg/FPV 700mg/RTV 100mg BID, and MVC 300mg BID Plus FPV 1400mg/RTV 100mg QD regimens

Amprenavir (APV) is the active ingredient/ metabolite of Fosamprenavir (FPV). MVC minimum concentration (Cmin), maximum concentration (Cmax), and area under the plasma concentration-time curve (AUC), as determined from MVC concentrations observed in blood samples obtained at baseline, and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours during the period when MVC 300mg BID was administered with the FPV-Containing BID regimens (FPV 1400mg BID, FPV 700mg/RTV 100 mg BID), and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 24 hours during the period when MVC 300mg BID was administered with the FPV QD regimen (FPV 1400mg/RTV 100mg QD). As Groups A and B received the same regimens (albeit in different order), PK data for these two groups were collated, then assessed. For the same reason, PK data from Groups C and D regimens were collated before assessment, as were the PK data from Groups E and F.

Percentage of Participants With Plasma Human Immuno Deficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) Levels Less Than 50 Copies/Milliliter (mL)
Week 48
Log 10-transformed Human Immunodeficiency Virus Ribonucleic Acid (HIV-1 RNA) Levels at Baseline
Baseline

Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.

Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 24
Baseline and Week 24

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 HIV-1 RNA Levels at Week 48
Baseline and Week 48

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 viral load
Day 11
UK-427,857 pharmacokinetics
Days 1-11
Pharmacokinetic profile of UK-427,857
Days 1 and 10
Receptor saturation
Days 1, 5, 10, 11, 13, 15, 19, 40
Part 1: Area Under The Plasma Concentration-Time Curve From Time 0 to 12 Hours (AUC [0-12]) of Maraviroc
Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5

AUC (0-12) is the area under the plasma concentration versus time curve from time zero (pre-dose) to 12 hours post-dose.

Part 2: Area Under The Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC [0-24]) of Maraviroc
Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12, 24 hours post-dose on Day 10

AUC (0-24) is the area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose.

Part 1: Metabolite to Parent Ratio for Area Under the Concentration-Time Curve From Time 0 to 12 Hours for Maraviroc and Its Metabolites (MRAUC12)
Pre-dose, 0.5, 1, 2, 3, 4, 6, 9, 12 hours post-dose on Day 5

MRAUC12 is the ratio of AUC12 of maraviroc to AUC12 of maraviroc's metabolites. Metabolites of Maraviroc included PF-6857639, PF-6857640, PF-06927572 and PF-06927573. AUC12 is the area under the plasma concentration-time profile from time 0 to 12 hours post-dose.

Maraviroc plasma pharmacokinetic parameters: AUC12, Cmax, and C12h on Period 1, Day 5 and Periods 2 and 3, Day 10
25 days
Safety parameters: AEs, vital signs, ECG, body temperature and laboratory assessments, including haematology, clinical biochemistry and cardiac troponin
Approximately 5 weeks from first dose to the follow-up visit

To assess the safety and tolerability of single and repeat inhaled doses of GSK2339345 administered by an aqueous droplet inhaler

Assessment of oropharyngeal sensation perturbation via a 4 point scale
Approximately 5 weeks from first dose to the follow-up visit

To assess the changes in oropharyngeal sensation caused by single and repeat inhaled doses of GSK2339345 administered by an aqueous droplet inhaler

Maraviroc plasma pharmacokinetic parameters: AUCτ, Cmax, and Cτ.
Period 1, Day 5
Amprenavir and ritonavir plasma pharmacokinetic parameters: AUCτ, Cmax, and Cτ.
Period 2, Day 10
To estimate the effect of multiple dose maraviroc on the pharmacokinetics of digoxin.
21 days
Plasma and urine maraviroc concentrations for pharmacokinetic analysis
pre-48 hrs post dose
Adverse event monitoring
Day 0 to Day 3
Bood pressure, pulse rate
Day 0, Day 1, and Day 3
Blood and urine safety laboratory tests
Day 0 and Day 3
ECG
Day 0 and Day 3

Secondary Endpoints

Percentage of Participants With at Least 0.5 Log 10 Reduction in Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA)
Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84 and Week 96 or end of treatment (EOT)
Percentage of Participants With at Least 1.0 Log 10 Reduction in HIV-1 RNA
Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84 and Week 96 or EOT
Percentage of Participants Achieving HIV-1 RNA Below Limit of Quantification
Baseline, Week 4, Week 8, Week 12, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84 and Week 96 or EOT
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Study Design & Arms

AllocationNON_RANDOMIZED
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
1EXPERIMENTAL -
Group AACTIVE_COMPARATORPeriod 1-Maraviroc 300mg BID Period 2- Fosamprenavir 1400mg BID Period 3- Fosamprenavir 1400mg BID + Maraviroc 300mg BID
Group BACTIVE_COMPARATORPeriod 1-Maraviroc 300mg BID Period 2-Fosamprenavir 1400mg BID + Maraviroc 300mg BID Period 3-Fosamprenavir 1400mg BID
Group CACTIVE_COMPARATORPeriod 1-Maraviroc 300mg BID Period 2-Fosamprenavir 700mg BID + Ritonavir 100mg BID Period 3-Fosamprenavir 700mg BID + Ritonavir 100mg BID + Maraviroc 300mg BID
Group DACTIVE_COMPARATORPeriod 1-Maraviroc 300mg BID Period 2-Fosamprenavir 700mg BID + Ritonavir 100mg BID + Maraviroc 300mg BID Period 3-Fosamprenavir 700mg BID + Ritonavir 100mg BID
Group EACTIVE_COMPARATORPeriod 1-Maraviroc 300mg BID Period 2-Fosamprenavir 1400mg QD + Ritonavir 100mg QD Period 3- Fosamprenavir 1400mg QD + Ritonavir 100mg QD + Maraviroc 300mg BID
Group FACTIVE_COMPARATORPeriod 1-Maraviroc 300mg BID Period 2-Fosamprenavir 1400mg QD + Ritonavir 100mg QD + Maraviroc 300mg BID Period 3-Fosamprenavir 1400mg QD + Ritonavir 100mg QD
Arm AEXPERIMENTALmaraviroc (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 BEXPERIMENTALemtricitabine/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.
2PLACEBO_COMPARATOR -
3EXPERIMENTAL -
4EXPERIMENTAL -
5PLACEBO_COMPARATOR -
AEXPERIMENTAL -
BEXPERIMENTAL -
CEXPERIMENTAL -
DEXPERIMENTAL -
EPLACEBO_COMPARATOR -
Cohort 1EXPERIMENTALAfrican-Americans with No CYP3A5\*1 alleles (poor metabolizer)
Cohort 2EXPERIMENTALAfrican-Americans with One CYP3A5\*1 allele (intermediate metabolizer)
Cohort 3EXPERIMENTALAfrican-Americans with Two CYP3A5\*1 alleles (extensive metabolizer)
Cohort 4EXPERIMENTALCaucasians with No CYP3A5\*1 alleles (poor metabolizer)
MaravirocACTIVE_COMPARATOR -
Maraviroc + BoceprevirEXPERIMENTAL -
Maraviroc + TelaprevirEXPERIMENTAL -
Sequence 1EXPERIMENTALTreatment 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 2EXPERIMENTALTreatment 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
DigoxinACTIVE_COMPARATOR -
Digoxin + MaravirocEXPERIMENTAL -
Active groupOTHERmaraviroc dosing group

Interventions

NameTypeDescription
MaravirocDRUGMaraviroc 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.
FosamprenavirDRUG1400 mg BID, 700 mg BID or 1400 mg QD
RitonavirDRUG100 mg BID, 100 mg QD
Maraviroc (UK-427,857)DRUGmaraviroc (UK-427,857) 150 mg taken once daily, OBT + maraviroc (UK-427,857) 150 mg taken twice daily, or OBT alone.
optimized background therapyDRUG\[OBT (3-6 drugs based on treatment history and resistance testing)\]
PlaceboDRUGPatients 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.
Maraviroc (Part 1)DRUG300 mg twice daily x 5 days
Maraviroc (Part 2)DRUG150 mg once daily x 10 days
Darunavir/cobicistat (Part 2)DRUG800/150 mg once daily x 10 days
Maraviroc + BoceprevirDRUGMaraviroc 150 mg BID + Boceprevir 800 mg TID x 10 days with food
Maraviroc + TelaprevirDRUGMaraviroc 150 mg BID + Telaprevir 800 mg TID x 10 days with food
CombivirDRUG1 tablet: lamivudine 150mg, zidovudine 300mg
GSK2838510DRUGMaraviroc 300mg, lamivudine 150mg, zidovudine 300mg
Fosamprenavir/ritonavirDRUGfosamprenavir/ritonavir 700/100 mg BID x 10 days
Maraviroc + Fosamprenavir/ritonavirDRUGmaraviroc 300 mg BID + fosamprenavir/ritonavir 700/100 mg BID x 10 days
DigoxinDRUGOral Digoxin 0.25 mg single dose
maraviroc (Selzentry, Celsentri)DRUG12 subjects will receive a single dose of 300 mg maraviroc (two 150 mg maraviroc commercial tablets) under fasting conditions.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites16

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...

Countries:BrazilUnited StatesArgentinaAustraliaAustriaBelgiumCanadaChileCosta RicaDominican RepublicFranceGermanyGreeceHong KongIndiaIrelandItalyMalaysiaMexicoNetherlandsPortugalPuerto RicoRomaniaSpainSwitzerlandTaiwanUnited KingdomPolandSwedenSingapore
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Frequently asked questions about Maraviroc

What is Maraviroc used for?

Maraviroc is an investigational small molecule being studied for the treatment of Human Immunodeficiency Virus-1 (HIV-1) infections. It is being developed by GSK plc (ticker: GSK) and has completed clinical trials in patients with HIV infections, including those in Phase 2 and Phase 3 studies.

Who makes Maraviroc?

Maraviroc is being developed by GSK plc, a pharmaceutical company listed on the stock exchange under the ticker GSK. The drug is currently in clinical development for the treatment of HIV-1 infections, with completed trials in multiple countries.

What phase is Maraviroc in?

Maraviroc is in Phase 3 clinical development for the treatment of HIV-1 infections. It has completed four clinical trials, including a Phase 3 expanded access program, and is not yet approved by regulatory authorities. The drug remains investigational and is still in clinical development.

What clinical trials is Maraviroc in?

Maraviroc has completed four clinical trials, including NCT00098306 and NCT00098722, which were Phase 2 studies of Maraviroc in combination with optimized background therapy for HIV-1 infected subjects. NCT00426660 was a Phase 3 expanded access program, and NCT00643643 was a Phase 2 pharmacokinetics study.

What does Maraviroc target?

Maraviroc is a small molecule that targets the CCR5 receptor, which is involved in HIV-1 entry into cells. By blocking this receptor, the drug aims to prevent the virus from infecting healthy cells. This mechanism is being studied in clinical trials for the treatment of HIV-1 infections.

Is Maraviroc the same as UK-427,857?

Yes, Maraviroc is also known as UK-427,857. Clinical trials, such as NCT00098306 and NCT00098722, refer to the drug as Maraviroc (UK-427,857), confirming that these names refer to the same investigational compound being developed for HIV-1 infections.