Dose Ranging Study of GSK1265744 Plus Nucleoside Reverse Transcriptase Inhibitors for Induction of Human Immunodeficiency Virus-1 (HIV-1) Virologic Suppression Followed by Virologic Suppression Maintenance by GSK1265744 Plus Rilpivirine

ViiV Healthcare

Status and phase: Completed; Phase 2

Conditions: Infection, Human Immunodeficiency Virus; HIV Infections

Treatments: Drug: Efavirenz 600 mg; Drug: GSK1265744 10 mg; Drug: Abacavir/Lamivudine (ABC/3TC) or Tenofovir/Emtricitabine (TDF/FTC); Drug: GSK1265744 60 mg; Drug: GSK1265744 30 mg; Drug: Placebo; Drug: Rilpivirine 25 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01641809

116482

Details and patient eligibility

About

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.

Enrollment: 244 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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244 participants in 4 patient groups

Arm 1 GSK1265744 10 mg

Experimental group

Description:

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.

Treatment:

Drug: Rilpivirine 25 mg

Drug: Placebo

Drug: GSK1265744 10 mg

Drug: Abacavir/Lamivudine (ABC/3TC) or Tenofovir/Emtricitabine (TDF/FTC)

Arm 2 GSK1265744 30 mg

Experimental group

Description:

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.

Treatment:

Drug: Rilpivirine 25 mg

Drug: Placebo

Drug: GSK1265744 30 mg

Drug: Abacavir/Lamivudine (ABC/3TC) or Tenofovir/Emtricitabine (TDF/FTC)

Arm 3 GSK1265744 60 mg

Experimental group

Description:

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.

Treatment:

Drug: Rilpivirine 25 mg

Drug: Abacavir/Lamivudine (ABC/3TC) or Tenofovir/Emtricitabine (TDF/FTC)

Drug: GSK1265744 60 mg

Arm 4 Efavirenz 600 mg

Active Comparator group

Description:

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).

Treatment:

Drug: Abacavir/Lamivudine (ABC/3TC) or Tenofovir/Emtricitabine (TDF/FTC)

Drug: Efavirenz 600 mg