Study to Evaluate the Safety and Efficacy of Teropavimab and Zinlirvimab in Combination With Lenacapavir (GS-6207) in Virologically Suppressed Adults With HIV-1 Infection

Phase 1

Completed

• Conditions: HIV-1 Infection
• Interventions: Drug: Oral Lenacapavir; Drug: Subcutaneous Lenacapavir; Drug: Teropavimab; Drug: Zinlirvimab

• Registration Number: NCT04811040
• Lead Sponsor: Gilead Sciences

Brief Summary

The primary objective of this study is to evaluate the safety and tolerability of a combination of the broadly neutralizing antibodies (bNAbs) teropavimab (formerly GS-5423) and zinlirvimab (formerly GS-2872) in combination with the HIV capsid inhibitor lenacapavir (LEN).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-03-19
• Study First Submitted QC: 2021-03-19
• Study First Posted: 2021-03-23
• Study Start: 2021-04-08
• Primary Completion: 2023-04-18
• Status Verified: 2023-10
• Study Completion: 2023-10-17
• Last Update Submitted: 2023-10-26
• Last Update Posted: 2023-10-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

• On first-line antiretroviral therapy (ART) for ≥ 2 years prior to screening. A change in ART regimen ≥ 28 days prior to screening for reasons other than virologic failure (VF) (eg, tolerability, simplification, drug-drug interaction profile) is allowed

• No documented historical resistance to the current ART regimen

• Plasma HIV-1 RNA < 50 copies/mL at screening

• Documented plasma HIV-1 RNA < 50 copies/mL for ≥ 18 months preceding the screening visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable viremia, or "blip") prior to screening are acceptable.

• Proviral phenotypic sensitivity to both teropavimab and zinlirvimab at screening by the PhenoSense mAb Assay (Monogram Biosciences) for inclusion in the Primary Cohort; sensitivity at screening by the PhenoSense mAb Assay (Monogram Biosciences) to 1 mAb, either teropavimab or zinlirvimab, within 18 months prior to enrollment for inclusion in the optional Pilot Cohort

  -- In both cohorts, teropavimab sensitivity is defined as 90% inhibitory concentration (IC90) ≤ 2 μg/mL; zinlirvimab sensitivity is defined as IC90 ≤ 2 μg/mL;

• CD4+ count nadir ≥ 350 cells/μL

• Screening CD4+ count ≥ 500 cells/μL

• Availability of a fully active alternative ART regimen, in the opinion of the investigator, in the event of discontinuation of the current ART regimen with development of resistance

Key

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Exclusion Criteria

• Comorbid condition requiring ongoing immunosuppression
• Evidence of current hepatitis B virus (HBV) infection
• Evidence of current hepatitis C virus (HCV) infection (prior infection cleared spontaneously or with treatment is acceptable)
• History of opportunistic infection or illness indicative of Stage 3 HIV disease

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Optional Cohorts: Lenacapavir (LEN), Teropavimab, Zinlirvimab Dose C	Subcutaneous Lenacapavir	Optional cohort included participants from primary cohort who could not qualify for primary cohort at the study start. Participants in optional cohort will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose C followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose C.
Primary Cohorts: Lenacapavir (LEN), Teropavimab, Zinlirvimab Dose C	Subcutaneous Lenacapavir	Participants will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose C followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose C.
Optional Cohorts: Lenacapavir (LEN), Teropavimab, Zinlirvimab Dose C	Oral Lenacapavir	Optional cohort included participants from primary cohort who could not qualify for primary cohort at the study start. Participants in optional cohort will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose C followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose C.
Optional Cohorts: LEN, Teropavimab, Zinlirvimab Dose D	Oral Lenacapavir	Optional cohort included participants screened for primary cohort but could not qualify for primary cohort at the study start. Participants in optional cohort will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose D followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose D.
Optional Cohorts: LEN, Teropavimab, Zinlirvimab Dose D	Subcutaneous Lenacapavir	Optional cohort included participants screened for primary cohort but could not qualify for primary cohort at the study start. Participants in optional cohort will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose D followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose D.
Primary Cohorts: LEN, Teropavimab, Zinlirvimab Dose D	Oral Lenacapavir	Participants will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose D followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose D.
Optional Cohorts: Lenacapavir (LEN), Teropavimab, Zinlirvimab Dose C	Teropavimab	Optional cohort included participants from primary cohort who could not qualify for primary cohort at the study start. Participants in optional cohort will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose C followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose C.
Primary Cohorts: Lenacapavir (LEN), Teropavimab, Zinlirvimab Dose C	Oral Lenacapavir	Participants will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose C followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose C.
Primary Cohorts: LEN, Teropavimab, Zinlirvimab Dose D	Subcutaneous Lenacapavir	Participants will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose D followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose D.
Optional Cohorts: Lenacapavir (LEN), Teropavimab, Zinlirvimab Dose C	Zinlirvimab	Optional cohort included participants from primary cohort who could not qualify for primary cohort at the study start. Participants in optional cohort will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose C followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose C.
Primary Cohorts: LEN, Teropavimab, Zinlirvimab Dose D	Teropavimab	Participants will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose D followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose D.
Primary Cohorts: LEN, Teropavimab, Zinlirvimab Dose D	Zinlirvimab	Participants will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose D followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose D.
Optional Cohorts: LEN, Teropavimab, Zinlirvimab Dose D	Teropavimab	Optional cohort included participants screened for primary cohort but could not qualify for primary cohort at the study start. Participants in optional cohort will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose D followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose D.
Primary Cohorts: Lenacapavir (LEN), Teropavimab, Zinlirvimab Dose C	Teropavimab	Participants will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose C followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose C.
Primary Cohorts: Lenacapavir (LEN), Teropavimab, Zinlirvimab Dose C	Zinlirvimab	Participants will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose C followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose C.
Optional Cohorts: LEN, Teropavimab, Zinlirvimab Dose D	Zinlirvimab	Optional cohort included participants screened for primary cohort but could not qualify for primary cohort at the study start. Participants in optional cohort will begin treatment by receiving LEN Dose A + LEN Dose B + teropavimab + zinlirvimab Dose D followed by LEN Dose A on the next day. The last treatment regimen will include LEN Dose B + teropavimab + zinlirvimab Dose D.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs)	First dose date up to Week 26

Secondary Outcome Measures

Name	Time	Method
Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm	Week 26
Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm	Week 26
Proportion of Participants With Positive Anti-Teropavimab Antibodies	Week 26
Proportion of Participants With Positive Anti-zinlirvimab Antibodies	Week 26
Change from Baseline in CD4+ Cell Count at Week 26	Baseline; Week 26
Proportion of Participants Who Develop Treatment-Emergent Resistance to Lenacapvir (LEN), Teropavimab, and Zinlirvimab	Day 1 up to Week 26
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs)	First dose date up to Week 26
Pharmacokinetic (PK) Parameter: AUC0-t of Teropavimab, and Zinlirvimab, and LEN	Day 1 up to Week 52	AUC0-t is defined as the concentration of drug over time from time zero to time "t".
PK Parameter: AUClast of Teropavimab, and Zinlirvimab, and LEN	Day 1 up to Week 52	AUClast is defined as the concentration of drug from time zero to the last observable concentration.
PK Parameter: T1/2 of Teropavimab, and Zinlirvimab, and LEN	Day 1 up to Week 52	T1/2 is defined as the estimate of the terminal elimination half-life of the drug.
PK Parameter: Cmax of Teropavimab, and Zinlirvimab, and LEN	Day 1 up to Week 52	Cmax is defined as the maximum observed concentration of drug.
PK Parameter: Tmax of Teropavimab, and Zinlirvimab, and LEN	Day 1 up to Week 52	Tmax is defined as the time (observed time point) of Cmax.
PK Parameter: Tlast of Teropavimab, and Zinlirvimab, and LEN	Day 1 up to Week 52	Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug).
PK Parameter: Ct of Teropavimab, and Zinlirvimab, and LEN	Day 1 up to Week 52	Ct is the concentration at a particular time (t).

Trial Locations

Locations (23)

Perelman Center for Advanced Medicine at the Hospital of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

The Brody School of Medicine at East Carolina University, ECU Adult Specialty Care; 🇺🇸 Greenville, North Carolina, United States

Be Well Medical Center; 🇺🇸 Berkley, Michigan, United States

Ruane Clinical Research Group Inc.; 🇺🇸 Los Angeles, California, United States

University of Miami Miller School of Medicine Schiff Center for Liver Disease; 🇺🇸 Miami, Florida, United States

Indiana CTSI Clinical Research Center; 🇺🇸 Indianapolis, Indiana, United States

The Crofoot Research, INC.; 🇺🇸 Houston, Texas, United States

One Community Health; 🇺🇸 Sacramento, California, United States

Icahn School of Medicine at Mount Sinai-Clinical and Translational Research Center; 🇺🇸 New York, New York, United States

Peter Shalit, M.D.; 🇺🇸 Seattle, Washington, United States

Orlando Immunology Center; 🇺🇸 Orlando, Florida, United States

Midway Immunology and Research Center; 🇺🇸 Fort Pierce, Florida, United States

UCSD AntViral Research Center (AVRC); 🇺🇸 San Diego, California, United States

Mills Clinical Research; 🇺🇸 Los Angeles, California, United States

Triple O Research Institute, P.A; 🇺🇸 West Palm Beach, Florida, United States

Mercer University, Department of Internal Medicine; 🇺🇸 Macon, Georgia, United States

National Institutes of Health/Clinical Center; 🇺🇸 Bethesda, Maryland, United States

AXCES Research Group; 🇺🇸 Santa Fe, New Mexico, United States

St. Jude Children's Research Hospital; 🇺🇸 Memphis, Tennessee, United States

Central Texas Clinical Research; 🇺🇸 Austin, Texas, United States

Rosedale Health & Wellness; 🇺🇸 Huntersville, North Carolina, United States

Yale University; School of Medicine; AIDS Program; 🇺🇸 New Haven, Connecticut, United States

NC TraCS Institute-CTRC; University of North Carolina at Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States