|
| Overall Recruitment Status: Active, enrollment completed |
| |
| Official Title |
| A Phase IIb, Randomized, Partially Blind, Active Controlled, Dose-range Finding Study of GSK3640254 Compared to a Reference Arm of Dolutegravir, Each in Combination With Nucleoside Reverse Transcriptase Inhibitors, in HIV-1 Infected Antiretroviral Treatment-naive Adults |
| |
| Region |
Sponsors |
| California - Southern |
|
| |
| Acronym |
KP IRB No. |
|
12522 |
| |
| Study Type |
Phase |
| Clinical Trial |
Phase II |
| |
| Study Population Description |
| (Adult, Older Adult) with Documented HIV Infections |
| |
| Purpose |
| Infection with HIV-1 continues to be a serious health threat throughout the world, with more than 40 million individuals infected worldwide. The current standard of care treatment for HIV-1 is combination anti-retroviral therapy (cART) with recommendations to start regardless of cluster of differentiation 4 (CD4) plus (+) T-cell count, committing people living with HIV to lifelong, lifesaving therapy. However, the chronic exposure to cART has identified anti-retroviral (ARV)-associated long-term toxicities (central nervous system [CNS] or cardiovascular [CV] metabolic effects, renal disease), creating a need to address and prevent these co-morbidities. GSK3640254 is a next-generation HIV-1 maturation inhibitor (MI) and has completed a short-term, monotherapy, proof of concept (POC) Phase 2a study. This is a phase 2b, randomized, multicenter, parallel group, partially blind (to GSK3640254 doses [100, 150 and 200 milligrams {mg}]), active controlled clinical trial. It will aim to investigate the safety, efficacy and dose-response of GSK3640254 compared to dolutegravir (DTG), each given in combination with 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) (abacavir/lamivudine [ABC/3TC] or emtricitabine/tenofovir alafenamide [FTC/TAF]), in approximately 240 treatment-naïve HIV-1 infected adults. In the experimental arms, GSK3640254 will be administered in 3 blinded doses until the last participant completes their Week 48 study visit (Week 48 Secondary Endpoint study milestone). Thereafter, participants whose most recent HIV-1 ribonucleic acid (RNA) less than (<)50 copies/milliliters (c/mL) in the GSK3640254 arms will move into the Non-Randomised Phase and will be switched from their blinded dose to the open label optimal dose. Simultaneously, these participants will also be switched from their dual NRTI therapy to DTG. The total study duration will be approximately 7 years. |
| |
| Detailed Description |
|
| |
| Gender |
Age Limit |
| Male & Female |
18 years & older |
| |
- Participants must be 18 years of age inclusive, at the time of signing the informed consent
|
-
Treatment-naive, defined as no ARVs (in combination or monotherapy) received after the diagnosis of HIV-1 infection (for example [e.g.], use of Pre-exposure prophylaxis [PreP] meets inclusion
|
-
Documented HIV infection and Screening plasma HIV-1 RNA greater than or equal to (>=)1000 copies/mL
|
-
Screening CD4+ T-cell count >=350 cells/mm^3
|
-
Body weight >=50.0 kilograms (kg) (110 pounds [lbs]) for men and >=45.0 kg (99 lbs) for women and body mass index (BMI) greater than (>)18.5 kg/meter square (m^2)
|
|
|
-
Please contact study team for additional inclusion/exclusion criteria
|
- Any evidence of an active Center for Disease Control and Prevention (CDC) Stage 3 disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy
|
-
Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia
|
-
Presence of primary HIV-1 infection, evidenced by acute retroviral syndrome (e.g., fever, malaise, fatigue) and/or evidence of recent (within 3 months) documented viremia without antibody production and/or evidence of recent (within 3 months) documented seroconversion
|
-
Known history of liver cirrhosis with or without viral hepatitis co-infection
|
-
Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment)
|
-
Please contact study team for additional inclusion/exclusion criteria
|
|
| |
|
|
|
|
|
|
|
|
|
|
|
-
Molecular Mechanisms of Pharmacological Action
|
|
|
|
|
|
|
|
|
-
Sexually Transmitted Diseases
|
|
|
-
Sexually Transmitted Diseases, Viral
|
|
|
|
-
Immunologic Deficiency Syndromes
|
|
|
| |
|