A Study of Teropavimab and Zinlirvimab in Combination With Capsid Inhibitor Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection

Phase 2

Active, not recruiting

Conditions: HIV Infection

Interventions: Drug: Teropavimab
Drug: Antiretroviral Therapy
Drug: Zinlirvimab
Drug: Lenacapavir Tablet
Drug: Lenacapavir Injection

Registration Number: NCT05729568

Lead Sponsor: Gilead Sciences

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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 83

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 2. 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 2.
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 at screening or from protocol GS-US-536-5816 within 24 months prior to screening.
Screening clusters of differentiation 4 (CD4)+ T-cell count ≥ 200 cells/μL at screening visit 2.

Key

Exclusion Criteria

Comorbid condition requiring ongoing immunosuppression.
Evidence of hepatitis C virus (HCV) infection (prior infection cleared spontaneously or with treatment is acceptable)
Evidence of current hepatitis B virus (HBV) infection regardless of HBV surface antigen status, at the screening visit 2.
History of opportunistic infection or illness indicative of Stage 3 HIV disease.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Randomized Phase Treatment Group 1: LEN + TAB + ZAB	Teropavimab	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 6 months (Q6M) up to Week 52 in the Randomized Phase.
Randomized Phase Treatment Group 1: LEN + TAB + ZAB	Zinlirvimab	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 6 months (Q6M) up to Week 52 in the Randomized Phase.
Randomized Phase Treatment Group 1: LEN + TAB + ZAB	Lenacapavir Tablet	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 6 months (Q6M) up to Week 52 in the Randomized Phase.
Randomized Phase Treatment Group 1: LEN + TAB + ZAB	Lenacapavir Injection	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 6 months (Q6M) up to Week 52 in the Randomized Phase.
Randomized Phase Treatment Group 3: SBR	Antiretroviral Therapy	Participants in Stay on Baseline Regimen (SBR) group will continue their baseline oral antiretroviral therapy (ART) up to Week 52. ART included 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.
Extension Phase: Treatment Group 1: LEN + TAB + ZAB	Teropavimab	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.
Extension Phase: Treatment Group 1: LEN + TAB + ZAB	Zinlirvimab	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.
Extension Phase: Treatment Group 1: LEN + TAB + ZAB	Lenacapavir Injection	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.
Extension Phase Treatment Group 3: SBR	Teropavimab	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 be given the option to participate in the Extension Phase to switch from oral ART to LEN, TAB and ZAB, every 26 weeks at the dose specified for Treatment Group 1.
Extension Phase Treatment Group 3: SBR	Zinlirvimab	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 be given the option to participate in the Extension Phase to switch from oral ART to LEN, TAB and ZAB, every 26 weeks at the dose specified for Treatment Group 1.
Extension Phase Treatment Group 3: SBR	Lenacapavir Tablet	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 be given the option to participate in the Extension Phase to switch from oral ART to LEN, TAB and ZAB, every 26 weeks at the dose specified for Treatment Group 1.
Extension Phase Treatment Group 3: SBR	Lenacapavir Injection	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 be given the option to participate in the Extension Phase to switch from oral ART to LEN, TAB and ZAB, every 26 weeks at the dose specified for Treatment Group 1.

Primary Outcome Measures

Name	Time	Method
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	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; 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 Outcome Measures

Name	Time	Method
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	Percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 26 was analyzed using the US FDA-defined snapshot algorithm, which defined a participant's virologic outcome and included participants who had the last available on-treatment HIV-1 RNA \< 50 copies/mL in the Week 26 analysis window. The Clopper-Pearson exact method was used to calculate the 95% CI for the outcome measure of each treatment. Percentages were rounded off.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 52 as Determined by the US FDA-defined Snapshot Algorithm	Week 52
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 is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.
Trough Concentration at Week 26 for LEN	Week 26	Trough concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.
Trough Concentration at Week 52 for TAB and ZAB	Week 52	Trough concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.
Trough Concentration at Week 52 for LEN	Week 52	Trough concentration is defined as the concentration of the drug in plasma/serum at the end of the dosing interval.
Pharmacokinetic (PK) Parameter: AUC0-tau for TAB and ZAB	Up to approximately 6 years	AUC0-tau is defined as the partial area under the concentration versus time curve from time "0" to time "t".
PK Parameter: t1/2 for TAB and ZAB	Up to approximately 6 years	t1/2 is defined as the terminal elimination half-life.
PK Parameter: Cmax for TAB and ZAB	Up to approximately 6 years	Cmax is defined as the maximum observed concentration of drug.
PK Parameter: Cmax for LEN	Up to approximately 6 years	Cmax is defined as the maximum observed concentration of drug.
PK Parameter: Tmax for TAB, ZAB, and LEN	Up to approximately 6 years	Tmax is defined as the time (observed time point) of Cmax.
Percentage of Participants With Treatment-emergent Anti-TAB and Anti-ZAB Antibodies	Up to approximately 6 years	Anti-TAB and anti-ZAB antibodies incidence referred to the percentage of participants who have treatment-emergent anti-TAB and anti-ZAB antibodies among all participants evaluable for anti-drug antibody (ADA) incidence.

Trial Locations

Locations (33): Ruane Clinical Research Group, Inc.
🇺🇸
Los Angeles, California, United States
Mills Clinical Research
🇺🇸
Los Angeles, California, United States
UC San Diego (UCSD) AntiViral Research Center (AVRC)
🇺🇸
San Diego, California, United States
Optimus Medical Group
🇺🇸
San Francisco, California, United States
University of Colorado Clinical and Translational Research Center
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Aurora, Colorado, United States
Yale University; School of Medicine; AIDS Program
🇺🇸
New Haven, Connecticut, United States
Georgetown University Medical Center
🇺🇸
Washington, District of Columbia, United States
Midland Florida Clinical Research Center, LLC
🇺🇸
DeLand, Florida, United States
Can Community Health Care
🇺🇸
Fort Lauderdale, Florida, United States
Midway Immunology and Research Center
🇺🇸
Fort Pierce, Florida, United States
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Ruane Clinical Research Group, Inc.
🇺🇸Los Angeles, California, United States