A Phase 2 Randomized, Open-label Study to Evaluate the Safety and Efficacy of Broadly Neutralizing Antibodies (bNAbs) GS-5423 and GS-2872 in Combination With the Capsid Inhibitor Lenacapavir as Long-Acting Treatment Dosed Every 6 Months in Virologically Suppressed Adults With HIV-1 Infection
Overview
- Phase
- Phase 2
- Intervention
- Teropavimab
- Conditions
- HIV-1 Infection
- Sponsor
- Gilead Sciences
- Enrollment
- 83
- Locations
- 67
- Primary Endpoint
- Percentage of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) ≥ 50 Copies/mL at Week 26 as Determined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm
- Status
- Active, Not Recruiting
- Last Updated
- 5 days ago
Overview
Brief Summary
The goal of this study is to test the effectiveness, safety, and tolerability of the combination of broadly neutralizing antibodies (bNAbs) (teropavimab (TAB; GS-5423) and zinlirvimab (ZAB; GS-2872)) with lenacapavir (LEN) in virologically suppressed adults with HIV-1 infection.
The purpose of this study is to evaluate the efficacy of switching to a regimen of LEN, TAB and ZAB, versus continuing on baseline oral antiretroviral therapy (ART) as determined by the proportion of participants with human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) ≥ 50 copies/mL at Week 26.
Detailed Description
Participants will be randomized in Treatment Groups 1 and 2 to receive LEN, TAB, and ZAB, with differing doses of TAB and ZAB between the 2 groups and in Treatment Group 3 to continue their baseline oral ART for 52 weeks. Eligible participants in Treatment Groups 1 through 3 will have the option of participating in the study extension phase to receive LEN, TAB and ZAB after completing study follow-up through Week 52. Treatment Group 2 was removed prior to dosing of all groups during Protocol Amendment 2.
Investigators
Eligibility Criteria
Inclusion Criteria
- •On stable oral antiretroviral therapy (ART) consisting of no more than 2 drug classes (with the exception of pharmacologic boosters cobicistat or ritonavir) for ≥ 1 year prior to screening visit
- •A change in ART regimen ≥ 28 days prior to screening visit 2 for reasons other than virologic failure (VF) (eg, tolerability, simplification, drug-drug interaction profile) is allowed.
- •No clinically significant documented historical resistance to the current ART regimen with the exception of isolated nucleoside reverse transcriptase inhibitor mutations including M184V or ≤ 2 thymidine analog mutations (TAMs: M41L, D67N, K70R, L210W, T215Y, and/or K219Q).
- •Plasma human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) \< 50 copies/mL at screening visit
- •Documented plasma HIV-1 RNA \< 50 copies/mL for ≥ 12 months preceding screening visit 2 (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Virologic elevations of ≥ 50 copies/mL (transient detectable viremia or "blips") prior to screening are acceptable.
- •Proviral phenotypic sensitivity to both teropavimab and zinlirvimab by the PhenoSense Assay (Monogram Biosciences).
- •Screening clusters of differentiation 4 (CD4)+ T-cell count ≥ 200 cells/μL at screening visit
Exclusion Criteria
- •Comorbid condition requiring ongoing immunosuppression.
- •Hepatitis C virus (HCV) antibody positive and HCV RNA detectable.
- •Evidence of current hepatitis B virus (HBV) infection regardless of HBV surface antigen status, at the screening visit
- •History of opportunistic infection or illness indicative of Stage 3 HIV disease.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Arms & Interventions
Randomized Phase Treatment Group 1: LEN + TAB + ZAB
Participants will receive loading dose of lenacapavir (LEN) 600 mg tablets, orally, on Day 1 and Day 2. They will receive LEN 927 mg subcutaneous (SC) injection along with teropavimab (TAB) 2550 mg intravenous (IV) infusion and zinlirvimab (ZAB) 2550 mg IV infusion on Day 1 and every 26 weeks up to Week 52 in the Randomized Phase. At Week 52, participants in this group with HIV-1 RNA \< 50 copies/mL will be given the option to participate in the study extension phase. In the study extension phase, participants will continue to receive their randomized study drugs every 26 weeks.
Intervention: Teropavimab
Randomized Phase Treatment Group 1: LEN + TAB + ZAB
Participants will receive loading dose of lenacapavir (LEN) 600 mg tablets, orally, on Day 1 and Day 2. They will receive LEN 927 mg subcutaneous (SC) injection along with teropavimab (TAB) 2550 mg intravenous (IV) infusion and zinlirvimab (ZAB) 2550 mg IV infusion on Day 1 and every 26 weeks up to Week 52 in the Randomized Phase. At Week 52, participants in this group with HIV-1 RNA \< 50 copies/mL will be given the option to participate in the study extension phase. In the study extension phase, participants will continue to receive their randomized study drugs every 26 weeks.
Intervention: Zinlirvimab
Randomized Phase Treatment Group 1: LEN + TAB + ZAB
Participants will receive loading dose of lenacapavir (LEN) 600 mg tablets, orally, on Day 1 and Day 2. They will receive LEN 927 mg subcutaneous (SC) injection along with teropavimab (TAB) 2550 mg intravenous (IV) infusion and zinlirvimab (ZAB) 2550 mg IV infusion on Day 1 and every 26 weeks up to Week 52 in the Randomized Phase. At Week 52, participants in this group with HIV-1 RNA \< 50 copies/mL will be given the option to participate in the study extension phase. In the study extension phase, participants will continue to receive their randomized study drugs every 26 weeks.
Intervention: Lenacapavir Tablet
Randomized Phase Treatment Group 1: LEN + TAB + ZAB
Participants will receive loading dose of lenacapavir (LEN) 600 mg tablets, orally, on Day 1 and Day 2. They will receive LEN 927 mg subcutaneous (SC) injection along with teropavimab (TAB) 2550 mg intravenous (IV) infusion and zinlirvimab (ZAB) 2550 mg IV infusion on Day 1 and every 26 weeks up to Week 52 in the Randomized Phase. At Week 52, participants in this group with HIV-1 RNA \< 50 copies/mL will be given the option to participate in the study extension phase. In the study extension phase, participants will continue to receive their randomized study drugs every 26 weeks.
Intervention: Lenacapavir Injection
Randomized Phase Treatment Group 3: SBR
Participants in Stay on Baseline Regimen (SBR) group will continue their baseline oral antiretroviral therapy (ART) up to Week 52. Antiretroviral therapy will include drugs like bictegravir/emtricitabine/tenofovir alafenamide, darunavir/cobicistat/emtricitabine/tenofovir alafenamide, dolutegravir/abacavir lamivudine, and rilpivirine/emtricitabine/tenofovir alafenamide, administered as per standard of care. At Week 52, participants in this group with HIV-1 RNA \< 50 copies/mL and in the absence of confirmed virologic rebound throughout the Randomized Phase of the study will switch from oral ART to LEN, TAB and ZAB, every 26 weeks. The participants will switch to receive LEN, TAB, and ZAB every 26 weeks beginning at Week 52.
Intervention: Antiretroviral Therapy
Extension Phase: Treatment Group 1: LEN + TAB + ZAB
At Week 52, participants in this group with HIV-1 RNA \< 50 copies/mL will be given the option to participate in the study extension phase. In the study extension phase, participants will receive LEN 927 mg SC, TAB 2550 mg IV infusion and ZAB 2550 mg IV infusion.
Intervention: Teropavimab
Extension Phase: Treatment Group 1: LEN + TAB + ZAB
At Week 52, participants in this group with HIV-1 RNA \< 50 copies/mL will be given the option to participate in the study extension phase. In the study extension phase, participants will receive LEN 927 mg SC, TAB 2550 mg IV infusion and ZAB 2550 mg IV infusion.
Intervention: Zinlirvimab
Extension Phase: Treatment Group 1: LEN + TAB + ZAB
At Week 52, participants in this group with HIV-1 RNA \< 50 copies/mL will be given the option to participate in the study extension phase. In the study extension phase, participants will receive LEN 927 mg SC, TAB 2550 mg IV infusion and ZAB 2550 mg IV infusion.
Intervention: Lenacapavir Injection
Extension Phase Treatment Group 3: SBR
At Week 52, participants in this group will be given the option to participate in the Extension Phase to switch from oral ART to LEN 927 mg SC, TAB 2550 mg IV infusion and ZAB 2550 mg IV infusion, every 26 weeks at the dose specified for Treatment Group 1.
Intervention: Teropavimab
Extension Phase Treatment Group 3: SBR
At Week 52, participants in this group will be given the option to participate in the Extension Phase to switch from oral ART to LEN 927 mg SC, TAB 2550 mg IV infusion and ZAB 2550 mg IV infusion, every 26 weeks at the dose specified for Treatment Group 1.
Intervention: Zinlirvimab
Extension Phase Treatment Group 3: SBR
At Week 52, participants in this group will be given the option to participate in the Extension Phase to switch from oral ART to LEN 927 mg SC, TAB 2550 mg IV infusion and ZAB 2550 mg IV infusion, every 26 weeks at the dose specified for Treatment Group 1.
Intervention: Lenacapavir Tablet
Extension Phase Treatment Group 3: SBR
At Week 52, participants in this group will be given the option to participate in the Extension Phase to switch from oral ART to LEN 927 mg SC, TAB 2550 mg IV infusion and ZAB 2550 mg IV infusion, every 26 weeks at the dose specified for Treatment Group 1.
Intervention: Lenacapavir Injection
Outcomes
Primary Outcomes
Percentage of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) ≥ 50 Copies/mL at Week 26 as Determined by the United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm
Time Frame: Week 26
Percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 26 was analyzed using US FDA-defined snapshot algorithm, which defines a participant's virologic outcome and included participants a) who had last available on-treatment HIV-1 RNA ≥ 50 copies/mL in the Week 26 analysis window; or b) who did not have on-treatment HIV-1 RNA data in the Week 26 analysis window and i) discontinued study drug prior to or in the Week 26 analysis window due to lack of efficacy, or ii) discontinued study drug prior to or in the Week 26 analysis window due to adverse event (AE) or death and had last available on-treatment HIV-1 RNA ≥ 50 copies/mL, or iii) discontinued study drug prior to or in the Week 26 analysis window due to reasons other than AE, death, or lack of efficacy and had the last available on-treatment HIV-1 RNA ≥ 50 copies/mL. Clopper-Pearson exact method was used to calculate the 95% confidence interval (CI) for the outcome measure of each treatment. Percentages were rounded off.
Secondary Outcomes
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 52 as Determined by the US FDA-defined Snapshot Algorithm(Week 52)
- Trough Concentration at Week 26 Predose for TAB and ZAB(Week 26 predose)
- Trough Concentration at Week 26 Predose for LEN(Week 26 predose)
- Trough Concentration at Week 52 Predose for TAB and ZAB(Week 52 predose)
- Trough Concentration at Week 52 Predose for LEN(Week 52 predose)
- Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 52 as Determined by the US FDA-defined Snapshot Algorithm(Week 52)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm(Week 26)
- Change From Baseline in Clusters of Differentiation 4 (CD4) + T-cell Counts at Week 26(Baseline, Week 26)
- Change From Baseline in CD4+ T-cell Counts at Week 52(Baseline, Week 52)
- Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)(Up to approximately 6 years)
- Trough Concentration at Week 26 for TAB and ZAB(Week 26)
- Trough Concentration at Week 26 for LEN(Week 26)
- Trough Concentration at Week 52 for TAB and ZAB(Week 52)
- Trough Concentration at Week 52 for LEN(Week 52)
- Pharmacokinetic (PK) Parameter: AUC0-tau for TAB and ZAB(Up to approximately 6 years)
- PK Parameter: t1/2 for TAB and ZAB(Up to approximately 6 years)
- PK Parameter: Cmax for TAB and ZAB(Up to approximately 6 years)
- PK Parameter: Cmax for LEN(Up to approximately 6 years)
- PK Parameter: Tmax for TAB, ZAB, and LEN(Up to approximately 6 years)
- Percentage of Participants With Treatment-emergent Anti-TAB and Anti-ZAB Antibodies(Up to approximately 6 years)