HIV-1-Infection
Conditions
Brief summary
The goal of this clinical study is to learn more about the experimental drugs GS-1720 and GS-4182; to compare the combination of GS-1720 and GS-4182 with the current standard-of-care treatment bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, BVY), 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. This study has two phases: Phase 2 and Phase 3. The primary objectives of this study are: Phase 2: To evaluate the efficacy of switching to oral weekly GS-1720 in combination with GS-4182 versus continuing BVY in virologically suppressed people with HIV-1 (PWH) at Week 24. Phase 3: To evaluate the efficacy of switching to oral weekly GS-1720/GS-4182 Fixed-dose combination (FDC) tablet regimen versus continuing BVY in virologically suppressed 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 (Treatment Group 1, Treatment Group 2, and Extension Phase) arms and Phase 3 Extension Phase arm are open-label; Phase 3 Treatment Group 1 and Phase 3 Treatment Group 2 arms are blinded.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 24 weeks before and at screening. * Receiving BVY for ≥ 24 weeks prior to screening. Key
Exclusion criteria
* Prior use of, or exposure to LEN, GS-1720, or GS-4182. * History of virologic failure while on an integrase strand-transfer inhibitor (INSTI)-based regimen. * Documented integrase strand-transfer inhibitor (INSTI) resistance, specifically, resistance-associated mutations (RAMs) E92G/Q, G118R, F121Y, Y143C/H/R, S147G, Q148H/K/R, N155H/S, or R263K in the integrase gene. * Prior use of any long-acting (LA) parenteral antiretrovirals (ARV) such as monoclonal antibodies (mAbs) or broadly neutralizing antibodies (bNAbs) targeting HIV-1, injectable cabotegravir (including oral cabotegravir lead-in), or injectable rilpivirine. * Any of the following laboratory values at screening: * Clusters of differentiation 4 (CD4) cell count \< 200 cells/mm\^3 at screening * Glomerular filtration rate \< 60 mL/min according to the Modification of Diet in Renal Disease formula * Hepatic transaminases (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \> 1.5 × upper limit of normal (ULN) * Direct bilirubin \> 1.5 × ULN * Platelets count \< 50,000 cells/mm\^3 * Hemoglobin \< 8.0 g/dL * Active or occult hepatitis B virus (HBV) infection. * Active hepatitis C virus (HCV). 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 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 Clusters of Differentiation 4 (CD4+) T-cell Count at Week 12 | Baseline, Week 12 | — |
| Phase 2: Change From Baseline in CD4+ T-cell Count at Week 24 | Baseline, Week 24 | — |
| Phase 2: Change From Baseline in CD4+ T-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: Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Determined by the US FDA-defined Snapshot Algorithm | Week 24 | — |
| Phase 2: PK Parameter: Tmax of GS-1720 and LEN | Day 1 up to Week 48 | Tmax is defined as the time (observed time point) of Cmax. |
| Phase 2: PK Parameter: Ctau of GS-1720 and LEN | Day 1 up to Week 48 | 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 | Day 1 up to Week 48 | 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: 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 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 CD4+ T-cell Count at Week 48 | Baseline, Week 48 | — |
| Phase 3: Change From Baseline in CD4+ T-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: Proportion 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 | — |
| Phase 2: Pharmacokinetic (PK) Parameter: Cmax of GS-1720 and Lenacapavir (LEN) | Day 1 up to Week 48 | Cmax is defined as the maximum observed concentration of drug. |
| 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 | — |
Countries
Puerto Rico, United States
Outcome results
None listed