HIV-1-infection
Conditions
Brief summary
The goal of this clinical study is to compare how effective a long-acting treatment of injectable combination of lenacapavir (LEN), teropavimab (TAB), and zinlirvimab (ZAB) is versus continuing a daily oral HIV treatment in adults with HIV-1 whose virus is already well controlled, after 1 year (52 weeks) of treatment. The primary objective of this study is to evaluate the efficacy of switching to the regimen of LEN, TAB, and ZAB versus continuing an oral stable baseline regimen (SBR) in virologically suppressed people with HIV-1 (PWH) as determined by the proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 52.
Interventions
DRUGLenacapavir
Administered subcutaneously
Administered orally
DRUGTeropavimab
Administered intravenously (IV)
DRUGZinlirvimab
Administered IV
DRUGSBR
SBRs administered orally. SBRs include medicines like bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir (DTG)+ tenofovir alafenamide (TAF)+ emtricitabine (FTC).
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Human immunodeficiency virus type 1 (HIV-1) susceptibility results from screening meeting specific criteria: 1\) Proviral phenotypic susceptibility to both TAB and ZAB by the investigational protocol-defined assay at screening. * Plasma HIV-1 RNA levels \< 50 copies/mL at screening. * At least 1 documented HIV-1 RNA level measured between 6 months and 12 months (+2 months) prior to screening. This and any other HIV-1 RNA measurements documented in this period must be \< 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). A single virologic elevation of ≥ 50 copies/mL and \< 400 copies/mL (transient detectable viremia or "blips") prior to screening are acceptable if the subsequent plasma HIV-1 RNA level is \< 50 copies/mL. * A plasma HIV-1 RNA test \< 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL) within the last 6 months prior. * If \> 1 plasma HIV-1 RNA measurements in the last 6 months prior to screening are available, all must be \< 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). * On a stable oral antiretroviral (ARV) therapy (ART) for ≥ 6 months prior to screening. * A change in ART regimen ≥ 3 months prior to the screening visit for reasons other than virologic failure (eg, tolerability, simplification, drug-drug interaction profile) is allowed; individuals with a change in ART regimen ≥ 3 months prior to screening must have been on the regimen for ≥ 3 months prior to screening, and all HIV-1 RNA measurements in that period must be \< 50 copies/mL. There are no permitted changes to ART regimens between screening and Day 1. Key
Exclusion criteria
* History of an opportunistic infection or illness indicative of Stage 3 HIV disease. * Known hypersensitivity to the study intervention, its metabolites, or formulation excipients. * Active, serious infections (other than HIV-1) requiring therapy \< 30 days prior to randomization. * Active tuberculosis infection. * Acute hepatitis of any cause \< 30 days before randomization. * History of, or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding) or severe hepatic impairment (Child-Pugh Class C). * Active malignancy requiring acute systemic therapy. * Have poor venous access that would limit phlebotomy or intravenous (IV) infusion of study drugs. * Prior use of, or exposure to, LEN or a broadly neutralizing antibody (bNAb) for HIV-1. * Prior use of, or exposure to, long-acting (LA) injectable cabotegravir (CAB) or LA injectable rilpivirine (RPV). * Prior use of, or exposure to, ibalizumab, fostemsavir, or maraviroc. * Current use of, or exposure to, nevirapine or zidovudine. * Baseline regimen consisting of monotherapy with any single ARV. * Treatment with immunosuppressant therapies (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies) within 4 weeks of screening (with the exception of a single short course of corticosteroids lasting ≤ 7 days) or have a comorbid condition with an anticipated need ongoing immunosuppressive treatment during the study. * Hepatitis C virus (HCV) antibody positive and HCV RNA detectable. * Chronic hepatitis B virus (HBV) infection, as determined by either: 1. Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV core antibody status, at the screening visit. 2. Positive HBV core antibody and negative HBV surface antibody, regardless of HBV surface antigen status, at the screening visit. Note: Individuals found to be susceptible to HBV infection (eg, negative hepatitis B surface antibody at the screening visit, regardless of prior HBV vaccination history) should be recommended to receive an HBV vaccination. Those who remain non-immune will receive regular testing for HBV. * Severe renal impairment-estimated glomerular filtration rate \< 30 mL/min according to the Cockcroft-Gault formula. * Abnormal electrocardiogram (ECG) at the screening visit that is clinically significant, as determined by the investigator. * Any of the following laboratory values at screening: 1. Alanine aminotransferase \> 5 × upper limit of normal (ULN). 2. Direct bilirubin \> 1.5 × ULN 3. Platelets \< 50,000/mm\^3. 4. Hemoglobin \< 8.0 g/dL. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 52 as Defined by the United States (US) Food and Drug Administration (FDA) Snapshot Algorithm. | Week 52 |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 92 as Defined by the US FDA Snapshot Algorithm. | Week 92 |
| Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 52 as Determined by the US FDA Snapshot Algorithm. | Week 52 |
| Proportion of Participants With HIV-1 RNA < 50 copies/mL at Week 92 as Determined by the US FDA Snapshot Algorithm. | Week 92 |
| Changes from Baseline in Clusters of Differentiation 4 (CD4)+ T-cell Counts at Week 52 | Baseline, Week 52 |
| Changes from Baseline in CD4+ T-cell Counts at Week 92 | Baseline, Week 92 |
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs) | First dose up to 92 weeks |
| Percentage of Participants Prematurely Discontinuing Their Study Treatment due to an AE | First dose up to 92 weeks |
| Trough Concentrations for LEN, TAB, and ZAB at Week 26 | Week 26 |
| Trough Concentrations for LEN, TAB, and ZAB at Week 52 | Week 52 |
| Trough Concentrations for LEN, TAB, and ZAB at Week 104 | Week 104 |
| Percentages of Participants With Antidrug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) to TAB | Up to 92 Weeks |
| Percentages of Participants With ADAs and NAbs to ZAB. | Up to 92 Weeks |
Contacts
CONTACTGilead Clinical Study Information Center
STUDY_DIRECTORGilead Study Director
Gilead Sciences
Outcome results
None listed