Clinical trial NCT01231555
Conditions: Infection, Human Immunodeficiency Virus
Keywords: antiretroviral HAART NNRTI emtricitabine Sexually Transmitted Disease antiretroviral therapy (ART)-naive adults Immunologic Deficiency Syndrome tenofovir abacavir Retroviridae Infections GSK2248761 lamivudine Acquired ImmunoDeficiency Syndrome (AIDS) HIV infection efavirenz
Sponsor: ViiV Healthcare
Start date: 2010-11-18; Completion date: 2011-07-04
Enrollment: 23 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This 96 week, Phase 2b study in 150 HIV-1 infected antiretroviral (ART) naive adult subjects consists of a dose-ranging evaluation of GSK2248761 at blinded doses of 100 mg and 200 mg once daily with a control arm of open-label efavirenz (EFV) 600 mg once daily. The background ART for all 3 arms will be chosen by the Investigators and will be either abacavir/lamivudine \[ABC/3TC\] or tenofovir/emtricitabine \[TDF/FTC\] fixed dose combination (FDC) tablets. Antiviral activity, safety, PK, and development of viral resistance will be evaluated.

Detailed description:
Study SGN113404 is a phase 2b randomized, partially blinded, multicenter, parallel group, dose-ranging study. The study will be conducted in approximately 150 HIV-1 infected ART naïve subjects. The background NRTIs to be co-administered with GSK2248761 or EFV will be selected by Investigators prior to randomization and will be either abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) fixed dose combination (FDC) tablets.

Subjects will participate in a Screening period (Day -28 to Day -1). Subjects may be re-screened once. Subjects will be randomized 1:1:1 to receive 100 mg of GSK2248761 once daily (50 subjects), 200 mg of GSK2248761 once daily (50 subjects) or 600 mg of EFV once daily (50 subjects). All three arms will be combined with either 300 mg/200 mg TDF/FTC or 600 mg/300 mg ABC/3TC, as chosen by the Investigator. The Investigators and subjects will be blinded to the dose of GSK2248761 being administered but will know whether they receive EFV or GSK2248761. The randomization will be stratified by HIV-1 viral load (VL) at screening, \< 100,000 copies/mL or \>/ 100,000 copies/mL as well as the choice of backbone NRTI, TDF/FTC or ABC/3TC.

This study will be enrolled in two stages. The first stage of the study will enroll approximately 30 subjects, at which time enrollment will be paused. An analysis of safety and tolerability will be reviewed by a safety review committee (SRC) once all subjects enrolled in Stage 1 reach Week 4. The SRC review will determine if the safety and tolerability profile of GSK2248761 supports the continuation of the trial and enrollment of an additional 120 subjects. All subjects will continue on study medications during this Week 4 analysis.

Additional analyses will be conducted once all subjects complete Week 4, Week 16, Week 24 and Week 48. A second review of the safety and tolerability of GSK2248761 will be performed by the SRC once all subjects reach Week 4. There will not be a pause in the study during the Week 4 analysis of all subjects.

The Week 16 and Week 24 analyses will be used respectively to select and confirm the optimal dose of GSK2248761 for continuation. This dose will be selected based on a statistical analysis of antiviral activity, safety and tolerability criteria. If, after confirmation of the optimal dose of GSK2248761 by the Week 24 analysis, both doses are considered acceptable based on efficacy, safety and PK data, then both arms will be continued through Week 48.

Beyond Week 48, those subjects who were randomized to the non-selected dose of GSK2248761 and have not met any criteria for discontinuation will be given the option to switch to the selected dose of GSK2248761 or to discontinue permanently from the study. Once they have switched to the selected dose they will be in the Open-Label phase of the study through Week 96. After Week 96, subjects receiving GSK2248761 will be given the option to continue to receive GSK2248761 until it is locally approved and commercially available, as long as they continue to derive clinical benefit without a protocol-defined reason for discontinuation.

Subjects randomized to EFV will have the option to continue to receive EFV through Week 96 unless they meet a protocol-defined reason for discontinuation. All subjects will have the option to continue TDF/FTC or ABC/3TC through Week 96. After Week 96, subjects will be expected to obtain local access to all commercially available ART.

Randomization will be stratified by:

* HIV-1 RNA \< or \>/ 100,000 copies/mL at screening
* Use of ABC/3TC or TDF/FTC FDC tablets as initial background ART

Switch of a background NRTI for toxicity management to an alternative marketed NRTI is allowed once. Switches of a background NRTI for any other reason are not permitted in the study. A switch of GSK2248761 or EFV is not allowed.

Study Endpoints /Assessments: Subjects will have assessments performed which will include baseline demographics, disease characteristics, and safety (laboratory and clinical evaluations). On study safety, efficacy, virologic, immunologic, and PK evaluations will be conducted.

Primary Endpoint: The proportion of subjects with HIV-1 RNA \<50copies/mL at Week 16. Dose selection will be based primarily on antiviral activity and tolerability in conjunction with immunologic, safety, virologic resistance and PK measures. Data from the Week 24 analysis will be used to confirm dose selection.

ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship

Arms: arm 1: In combination with either abacavir/lamivudine FDC qd or tenofovir/emtricitabine FDC qd arm 2: In combination with either abacavir/lamivudine FDC qd or tenofovir/emtricitabine FDC qd arm 3: In combination with either abacavir/lamivudine FDC qd or tenofovir/emtricitabine FDC qd
Interventions: intervention 1: GSK2248761 100 mg once daily intervention 2: GSK2248761 200 mg once daily intervention 3: Efavirenz 600 mg once daily
Intervention descriptions: intervention 1: 1x100 mg capsule plus matching placebo intervention 2: 2x100 mg capsules intervention 3: 1x600mg tablet

Protocol documents: