Conditions: Infection, Human Immunodeficiency Virus
Keywords: raltegravir NNRTI ritonavir darunavir HIV GSK2248761 antiretroviral HIV Infection HAART
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 30
Healthy volunteers: no

Brief summary:
This 48 week, phase 2b study in 150 HIV-1 infected antiretroviral therapy experienced 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 etravirine (ETV) 200 mg twice daily. The background ART for all three arms will be darunavir/ritonavir (DRV/r) 600 mg/100 mg twice daily plus raltegravir (RAL) 400 mg twice daily. Antiviral activity, safety, PK, and development of viral resistance will be evaluated.

Detailed description:
Study SGN113399 is a Phase 2b randomized, partially-blinded, multicenter, parallel-group, dose-ranging study to be conducted in HIV-1 infected ART-experienced adults with documented NNRTI resistance.

A minimum of 150 subjects will be randomized 1:1:1 to one of two GSK2248761 doses or a control regimen containing ETV (50 subjects per group); all subjects will also receive darunavir/ritonavir and raltegravir. The trial will be partially blinded, i.e. subjects receiving GSK2248761 and the investigators will be blinded to the dose they receive. Subjects will not be blinded to whether they receive GSK2248761 or ETV.

Randomization will be stratified by:

* HIV-1 VL at screening, \<50,000 copies/mL or \>/50,000 copies/mL, and
* Darunavir susceptibility (screening phenotype fold change \<7 or \>/7 to 20)

Background ART will be administered open-label.

The primary endpoint analysis will take place after all subjects have completed Week 16. An optimal dose of GSK2248761 will be determined by the Week 16 analysis; this dose selection will be confirmed using an analysis from all subjects following completion of Week 24. If there is a clear efficacy, safety or tolerability advantage driving dose selection for GSK2248761, then all subjects receiving the non-selected dose of GSK2248761 will be switched to the selected dose following dose confirmation, after all subjects have completed Week 24. If no differentiation of dose can be made based on objective measures of efficacy, safety or tolerability, then both doses will be continued through Week 48.

After Week 48, all subjects will be expected to obtain local access to all commercially available ART.

No regimen switches of either background ART (DRV/r and RAL) or test agent or control (GSK2248761 and ETV) are allowed during the 48 week period of the study.

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

The primary endpoint will be 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 darunavir/ritonavir BID and raltegravir BID arm 2: In combination with darunavir/ritonavir BID and raltegravir BID arm 3: In combination with darunavir/ritonavir BID and raltegravir BID

Interventions: intervention 1: GSK2248761 100 mg once daily intervention 2: GSK2248761 200 mg once daily intervention 3: Etravirine
Intervention descriptions: intervention 1: 1 100mg capsule OAD plus matching placebo intervention 2: 2 100mg capsules OAD intervention 3: 2 100mg tablets twice daily

Protocol document: