Infection, Human Immunodeficiency Virus Clinical Trial
Official title:
A Phase 2b Study to Select a Once Daily Oral Dose of GSK2248761 in HIV-1 Infected Antiretroviral Therapy Experienced Adults With Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI) Resistance
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.
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
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