HIV-1-infection
Conditions
Brief summary
The goal of this clinical study is to learn more about the experimental drugs GS-1720 (an oral, long-acting integrase strand transfer inhibitor (INSTI)) and GS-4182 (a prodrug of Lenacapavir (LEN)); to compare the combination of GS-1720 and GS-4182 with the current standard-of-care treatment bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (Biktarvy), to see if the combination of GS-1720 and GS-4182 is safe and if it works for treating human immunodeficiency virus type 1 (HIV-1) infection in treatment-naive people with HIV-1 (PWH). This study has two phases: Phase 2 and Phase 3. The primary objectives of this study are: Phase 2: To evaluate the efficacy of oral weekly GS-1720 coadministered with GS-4182 versus continuing Biktarvy (BVY) in treatment-naive PWH at Week 24. Phase 3: To evaluate the efficacy of oral weekly GS-1720/GS-4182 fixed-dose combination (FDC) tablet regimen versus continuing BVY in treatment-naive PWH at Week 48.
Interventions
DRUGGS-1720
Tablets administered orally without regard to food
DRUGGS-4182
Tablets administered orally without regard to food
Tablets administered orally without regard to food
Tablets administered orally without regard to food
Tablets administered orally without regard to food
Tablets administered orally without regard to food
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Phase 2 of the study has 2 periods: Randomized and Extension, which are both open label. Phase 3 of the study has 2 periods: Randomized Period which would be double-blind (at least Week 96), followed by an Extension Period which will be Open-label.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * HIV-1 RNA ≥ 500 copies/mL at screening. * Antiretroviral (ARV) treatment-naive, except the use of oral pre-exposure prophylaxis (PrEP) or postexposure prophylaxis (PEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or F/TAF, up to 1 month prior to screening. Key
Exclusion criteria
* Prior use of any long acting parenteral antiretrovirals (ARVs) such as monoclonal antibodies, broadly neutralizing antibodies targeting HIV-1, LEN, injectable cabotegravir (including oral cabotegravir lead-in), and/or injectable rilpivirine. * Documented resistance to the integrase strand-transfer inhibitor class, specifically, resistance-associated mutations E92G/Q, G118R, F121Y, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene. * Any of the following laboratory values at screening: 1. CD4 cell count \< 200 cells/mm3 at screening. 2. Estimated glomerular filtrations arate \< 60 mL/min according to the Modification of Diet in Renal Disease formula. 3. Hepatic transaminases (aspartate aminotransferase and alanine aminotransferase) \> 1.5 × upper limit of normal (ULN). 4. Direct bilirubin \> 1.5 × ULN. 5. Platelets count \< 50,000 cells/mm3. 6. Hemoglobin \< 8.0 g/dL. * Active or occult hepatitis B virus infection. * Active hepatitis C virus infection. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 2: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the United States (US) Food and Drug Administration (FDA)-defined Snapshot Algorithm | Week 24 |
| Phase 3: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm | Week 48 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 2: Proportion of Participants With HIV-1 RNA < 50 copies/mL at Week 12 as Determined by the US FDA-defined Snapshot Algorithm | Week 12 | — |
| Phase 2: Proportion of Participants With HIV-1 RNA < 50 copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm | Week 48 | — |
| Phase 2: Change From Baseline in log10 HIV-1 RNA at Week 12 | Baseline, Week 12 | — |
| Phase 2: Change From Baseline in log10 HIV-1 RNA at Week 24 | Baseline, Week 24 | — |
| Phase 2: Change From Baseline in log10 HIV-1 RNA at Week 48 | Baseline, Week 48 | — |
| Phase 2: Change From Baseline in Clusters of Differentiation 4 (CD4) Cell Count at Week 12 | Baseline, Week 12 | — |
| Phase 2: Change From Baseline in CD4 Cell Count at Week 24 | Baseline, Week 24 | — |
| Phase 2: Change From Baseline in CD4 Cell Count at Week 48 | Baseline, Week 48 | — |
| Phase 2: Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) Through Week 12 | First dose date up to Week 12 | — |
| Phase 2: Percentage of Participants Experiencing TEAEs Through Week 24 | First dose date up to Week 24 | — |
| Phase 2: Percentage of Participants Experiencing TEAEs Through Week 48 | First dose date up to Week 48 | — |
| Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 12 | First dose date up to Week 12 | — |
| Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 24 | First dose date up to Week 24 | — |
| Phase 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 48 | First dose date up to Week 48 | — |
| Phase 2: Pharmacokinetic (PK) Parameter: Cmax of GS-1720 and Lenacapavir (LEN), as Applicable | Day 1 up to Week 24 | Cmax is defined as the maximum observed concentration of drug. |
| Phase 2: PK Parameter: Tmax of GS-1720 and LEN, as Applicable | Day 1 up to Week 24 | Tmax is defined as the time (observed time point) of Cmax. |
| Phase 2: PK Parameter: Ctau of GS-1720 and LEN, as Applicable | Day 1 up to Week 24 | Ctau is defined as the observed drug concentration at the end of the dosing interval. |
| Phase 2: PK Parameter: AUCtau of GS-1720 and LEN, as Applicable | Day 1 up to Week 24 | AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). |
| Phase 3: Proportion of Participants With HIV-1 RNA < 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm | Week 96 | — |
| Phase 3: Change From Baseline in log10 HIV-1 RNA at Week 48 | Baseline, Week 48 | — |
| Phase 3: Change From Baseline in log10 HIV-1 RNA at Week 96 | Baseline, Week 96 | — |
| Phase 3: Change From Baseline in CD4 Cell Count at Week 48 | Baseline, Week 48 | — |
| Phase 3: Change From Baseline in CD4 Cell Count at Week 96 | Baseline, Week 96 | — |
| Phase 3: Percentage of Participants Experiencing TEAEs Through Week 48 | First dose date up to Week 48 | — |
| Phase 3: Percentage of Participants Experiencing TEAEs Through Week 96 | First dose date up to Week 96 | — |
| Phase 3: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 48 | First dose date up to Week 48 | — |
| Phase 3: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities Through Week 96 | First dose date up to Week 96 | — |
Countries
Canada, Germany, Poland, Portugal, Puerto Rico, Romania, South Africa, Spain, United States
Contacts
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Outcome results
None listed