Overview

This trial is active, not recruiting.

Condition infection, human immunodeficiency virus
Treatments gsk1265744 10 mg, gsk1265744 30 mg, gsk1265744 60 mg, efavirenz 600 mg, rilpivirine 25 mg, placebo, abacavir/lamivudine (abc/3tc) or tenofovir/emtricitabine (tdf/ftc)
Phase phase 2
Sponsor ViiV Healthcare
Collaborator GlaxoSmithKline
Start date August 2012
End date October 2013
Trial size 244 participants
Trial identifier NCT01641809, 116482

Summary

The study is designed to select a dose of GSK1265744 primarily on the basis of antiviral activity and tolerability in HIV-1 infected, antiretroviral naive subjects.

This study consists of two parts:

Induction Phase: Approximately 200 subjects will be randomized (50 subjects in each of the 4 treatment arms). The Induction Phase consists of a 24 week dose-ranging evaluation of GSK1265744 at blinded doses of 10 mg, 30 mg and 60 mg once-daily and a control arm of open-label efavirenz (EFV) 600 mg once daily. The background dual nucleoside reverse transcriptase inhibitor (NRTI) antiretroviral therapy (ART) for all arms will be either abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) as selected by the Investigator. Subjects randomized to a GSK1265744 containing arm, who successfully complete 24 weeks on study and demonstrate virologic suppression (defined as having a plasma HIV-1 ribonucleic acid [RNA] <50 copies per milliliter [c/mL] before Week 24, with no signs of virologic rebound) will become eligible for the Maintenance Phase of this study.

Maintenance Phase: The background NRTIs will be discontinued and the subjects will continue their randomized dose of GSK1265744 in combination with rilpivirine (RPV) 25 mg once-daily for an additional 72 weeks. The Maintenance phase will evaluate the ability of this two drug ART regimen to maintain virologic suppression through Week 48, Week 72 and Week 96. Subjects randomized to the EFV arm will continue on their randomized regimen through Week 96.

After completion of the maintenance phase, subjects could enroll in the Open-Label Phase to continue GSK1265744 + RPV treatment as long as they continue to derive clinical benefit and until it is locally approved and commercially available.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
In the Induction Phase subjects will receive oral tablets of GSK1265744 10 mg + matching placebo + investigator-selected background NRTIs (either abacavir/lamivudine or tenofovir/emtricitabine) once daily from Day 1 to Week 24. Subjects continuing in the Maintenance Phase will receive oral tablets of GSK1265744 10 mg + matching placebo + Rilpivirine 25 mg once daily from Week 24 to Week 96.
gsk1265744 10 mg
GSK1265744 10 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase of the study and in combination with Rilpivirine 25 mg in the Maintenance Phase of the study.
rilpivirine 25 mg
Rilpivirine 25 mg will be administered orally once daily in combination with GSK1265744 10 mg, 30 mg and 60 mg in the Maintenance Phase of the study.
placebo
Placebo matching to GSK1265744 will be administered along with GSK1265744 10 mg and 30 mg in the Induction phase and Maintenance phase of the study.
abacavir/lamivudine (abc/3tc) or tenofovir/emtricitabine (tdf/ftc)
The background dual NRTI therapy for all arms in the Induction Phase and Efavirenz 600 mg arm in the Maintenance Phase will be either abacavir 600 mg + lamivudine 300 mg (ABC/3TC) or tenofovir 300 mg + emtricitabine 200 mg (TDF/FTC) as selected by the Investigator.
(Experimental)
In the Induction Phase subjects will receive oral tablets of GSK1265744 30 mg + matching placebo + investigator-selected background NRTIs (either abacavir/lamivudine or tenofovir/emtricitabine) once daily from Day 1 to Week 24. Subjects continuing in the Maintenance Phase will receive oral tablets of GSK1265744 30 mg + matching placebo + Rilpivirine 25 mg once daily from Week 24 to Week 96.
gsk1265744 30 mg
GSK1265744 30 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase of the study and in combination with Rilpivirine 25 mg in the Maintenance Phase of the study.
rilpivirine 25 mg
Rilpivirine 25 mg will be administered orally once daily in combination with GSK1265744 10 mg, 30 mg and 60 mg in the Maintenance Phase of the study.
placebo
Placebo matching to GSK1265744 will be administered along with GSK1265744 10 mg and 30 mg in the Induction phase and Maintenance phase of the study.
abacavir/lamivudine (abc/3tc) or tenofovir/emtricitabine (tdf/ftc)
The background dual NRTI therapy for all arms in the Induction Phase and Efavirenz 600 mg arm in the Maintenance Phase will be either abacavir 600 mg + lamivudine 300 mg (ABC/3TC) or tenofovir 300 mg + emtricitabine 200 mg (TDF/FTC) as selected by the Investigator.
(Experimental)
In the Induction Phase subjects will receive oral tablets of GSK1265744 60 mg + investigator-selected background NRTIs (either abacavir/lamivudine or tenofovir/emtricitabine) once daily from Day 1 to Week 24. Subjects continuing in the Maintenance Phase will receive oral tablets of GSK1265744 60 mg + Rilpivirine 25 mg once daily from Week 24 to Week 96.
gsk1265744 60 mg
GSK1265744 60 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase of the study and in combination with Rilpivirine 25 mg in the Maintenance Phase of the study.
rilpivirine 25 mg
Rilpivirine 25 mg will be administered orally once daily in combination with GSK1265744 10 mg, 30 mg and 60 mg in the Maintenance Phase of the study.
abacavir/lamivudine (abc/3tc) or tenofovir/emtricitabine (tdf/ftc)
The background dual NRTI therapy for all arms in the Induction Phase and Efavirenz 600 mg arm in the Maintenance Phase will be either abacavir 600 mg + lamivudine 300 mg (ABC/3TC) or tenofovir 300 mg + emtricitabine 200 mg (TDF/FTC) as selected by the Investigator.
(Active Comparator)
In the Induction Phase and Maintenance Phase subjects will receive oral tablets of Efavirenz 600 mg + investigator-selected background NRTIs (either abacavir/lamivudine or tenofovir/emtricitabine).
efavirenz 600 mg
Efavirenz 600 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase and Maintenance Phase of the study.
abacavir/lamivudine (abc/3tc) or tenofovir/emtricitabine (tdf/ftc)
The background dual NRTI therapy for all arms in the Induction Phase and Efavirenz 600 mg arm in the Maintenance Phase will be either abacavir 600 mg + lamivudine 300 mg (ABC/3TC) or tenofovir 300 mg + emtricitabine 200 mg (TDF/FTC) as selected by the Investigator.

Primary Outcomes

Measure
Proportion of subjects with HIV-1 RNA <50 copies/mL at Week 48
time frame: 48 weeks

Secondary Outcomes

Measure
Proportion of subjects with plasma HIV-1 RNA <400 and <50 copies/mL over time by visit
time frame: Through Week 96
Proportion of subjects with HIV-1 RNA <50 copies/mL at Week 16 and Week 24 in Induction Phase
time frame: 16 weeks, 24 weeks
The proportion of subjects with HIV-1 RNA <50 copies/mL from Week 24 through Week 96 by visit in Maintenance Phase
time frame: 24 weeks through Week 96
Absolute values and change from Baseline in plasma HIV-1 RNA by visit
time frame: Baseline (Study Day 1), and up to Week 96
Incidence of disease progression
time frame: Up to Week 96
Absolute values and changes from baseline in CD4+ cell counts by visit
time frame: Baseline (Study Day 1), and up to Week 96
Incidence of treatment emergent genotypic and phenotypic resistance to GSK1265744, RPV and other on-study ART for protocol-defined virologic failures
time frame: Up to Week 96
Incidence and severity of Adverse Events (AEs) and laboratory abnormalities over time
time frame: Up to Week 96
Absolute values and changes in laboratory parameters by visit
time frame: Up to Week 96
Proportion of subjects who discontinue treatment due to AEs
time frame: Up to Week 96
Incidence of any clinically significant changes in QRS duration, QTc interval, HR, PR interval based on electrocardiograph (ECG) readings by visit
time frame: Baseline (Study Day 1), and up to Week 96
Plasma GSK1265744 pharmacokinetic (PK) parameters [area under the concentration time curve over the dosing interval (AUC[0-tau]), maximum observed concentration (Cmax), and concentration at the end of a dosing interval (Ctau)]
time frame: 2 weeks, 12 weeks, 26 weeks, and 36 weeks (Pre-dose and 2 to 4 hours (h) post dose)
Plasma rilpivirine PK parameters [AUC(0-tau), Cmax, Ctau]
time frame: 2 weeks, 12 weeks, 26 weeks, and 36 weeks (Pre-dose and 2 to 4 hours (h) post dose)
Adherence to IP
time frame: Up to Week 96

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - HIV-1 infected male or female subjects >= 18 years of age - Screening plasma HIV-1 RNA >=1000 c/mL - CD4+ cell count >=200 cells/millimeter (mm)^3 - ART-naive defined as having =<10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection - Female subjects of child bearing potential are eligible to enter if they are not pregnant and willing to use protocol-specified methods of contraception to prevent pregnancy during the study Exclusion Criteria: - Any evidence at screening of an active Centers for Disease and Prevention Control (CDC) Category C disease - Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening - History of ongoing or clinically relevant hepatitis within the previous 6 months, and subjects with moderate to severe hepatic impairment will be excluded - Women who are breastfeeding - Subject, who in the investigator's judgment, poses a significant suicide risk - Any clinically significant finding on screening or baseline electrocardiograph (ECG) - The presence of any specific laboratory abnormalities at Screening - History of cardiac disease - Clinically relevant pancreatitis - Subjects who are unlikely to complete the dosing schedule due to a pre-existing physical or mental condition - Any condition which impairs the absorption, distribution, metabolism or excretion of the investigational product - Any evidence of primary resistance based upon the presence of a major resistance associated mutation in the Screening HIV genotype, or any historical genotype - Treatment with any protocol-specified excluded medication

Additional Information

Official title A Phase IIb, Dose Ranging Study of Oral GSK1265744 in Combination With Nucleoside Reverse Transcriptase Inhibitors for Induction of Human Immunodeficiency Virus -1 (HIV-1) Virologic Suppression Followed by an Evaluation of Maintenance of Virologic Suppression When Oral GSK1265744 is Combined With Oral Rilpivirine in HIV-1 Infected, Antiretroviral Therapy Naive Adult Subjects
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by ViiV Healthcare.