HIV-1 InfectionPhase 1NCT04811040
Study to Evaluate the Safety and Efficacy of Teropavimab and Zinlirvimab in Combination With Lenacapavir in Virologically Suppressed Adults With HIV-1 Infection
A Phase 1 study testing Oral Lenacapavir, Subcutaneous Lenacapavir and Teropavimab in people with HIV-1 Infection, run by Gilead Sciences at 23 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV-1 Infection
- What is being tested?
- Oral Lenacapavir, Subcutaneous Lenacapavir and Teropavimab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 23 sitesUnited States
- Study dates
- 8 Apr 2021to 26 Oct 2023
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
Show all 9Show fewer
- Cluster determinant 4+ (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
Who cannot join
- 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.
Trial locations and contacts
23 sites in 1 country.
23 sites in 1 country
United States23 sites
Central Texas Clinical Research
Austin, Texas, 78705
Be Well Medical Center
Berkley, Michigan, 48072
National Institutes of Health/Clinical Center
Bethesda, Maryland, 20892
NC TraCS Institute-CTRC; University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27514
Midway Immunology and Research Center
Ft. Pierce, Florida, 34982
The Brody School of Medicine at East Carolina University, ECU Adult Specialty Care
Greenville, North Carolina, 27834
The Crofoot Research, INC.
Houston, Texas, 77098
Rosedale Health & Wellness
Huntersville, North Carolina, 28078
Indiana CTSI Clinical Research Center
Indianapolis, Indiana, 46202
Ruane Clinical Research Group Inc.
Los Angeles, California, 90036
Mills Clinical Research
Los Angeles, California, 90069
Mercer University, Department of Internal Medicine
Macon, Georgia, 31201
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
University of Miami Miller School of Medicine Schiff Center for Liver Disease
Miami, Florida, 33136
Yale University; School of Medicine; AIDS Program
New Haven, Connecticut, 06510
Icahn School of Medicine at Mount Sinai-Clinical and Translational Research Center
New York, New York, 10029
Orlando Immunology Center
Orlando, Florida, 32803
Perelman Center for Advanced Medicine at the Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
One Community Health
Sacramento, California, 95811
UCSD AntViral Research Center (AVRC)
San Diego, California, 92103
AXCES Research Group
Santa Fe, New Mexico, 87505
Peter Shalit, M.D.
Seattle, Washington, 98104
Triple O Research Institute, P.A
West Palm Beach, Florida, 33407
About this study
Official title: A Phase 1b Randomized, Blinded, Proof-of-Concept Study to Evaluate the Safety and Efficacy of Broadly Neutralizing Antibodies (bNAbs) GS-5423 and GS-2872 in Combination With Capsid Inhibitor Lenacapavir (GS-6207) in Virologically Suppressed Adults With HIV-1 Infection
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).
- Conditions
- HIV-1 Infection
- Being tested
- Oral Lenacapavir, Subcutaneous Lenacapavir, Teropavimab, Zinlirvimab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral LenacapavirDrug
Also called GS-6207
Tablets administered without regard to food
Subcutaneous LenacapavirDrug
Also called GS-6207
Administered in the abdomen via subcutaneous injections
TeropavimabDrug
Also called 3BNC117-LS, GS-5423
Administered intravenously
ZinlirvimabDrug
Also called 10-1074-LS, GS-2872
Administered intravenously
| Study group | Role | What they receive |
|---|---|---|
| Primary Cohort: Lenacapavir (LEN) + Teropavimab + Zinlirvimab 10 mg/kg | Experimental | Participants will receive a loading dose of 600 milligrams (mg) LEN orally on Day 1 and Day 2, along with 927 mg LEN as subcutaneous (SC) injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an intravenous (IV) infusion on Day 1. Receives: Drug: Oral Lenacapavir; Drug: Subcutaneous Lenacapavir; Drug: Teropavimab; Drug: Zinlirvimab |
| Primary Cohort: LEN + Teropavimab + Zinlirvimab 30 mg/kg | Experimental | Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1. Receives: Drug: Oral Lenacapavir; Drug: Subcutaneous Lenacapavir; Drug: Teropavimab; Drug: Zinlirvimab |
| Pilot Cohort: LEN +Teropavimab +Zinlirvimab 10 mg/kg | Experimental | Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 10 mg/kg zinlirvimab as an IV infusion on Day 1. Receives: Drug: Oral Lenacapavir; Drug: Subcutaneous Lenacapavir; Drug: Teropavimab; Drug: Zinlirvimab |
| Pilot Cohort: LEN +Teropavimab +Zinlirvimab 30 mg/kg | Experimental | Participants will receive a loading dose of 600 mg LEN orally on Day 1 and Day 2, along with 927 mg LEN as SC injection on Day 1. Thereafter, participants will receive 30 mg/kg teropavimab and then 30 mg/kg zinlirvimab as an IV infusion on Day 1. Receives: Drug: Oral Lenacapavir; Drug: Subcutaneous Lenacapavir; Drug: Teropavimab; Drug: Zinlirvimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs)
A treatment emergent SAE was defined as an event that, at any dose, resulted in the following: death; life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; a congenital anomaly/birth defect; a medically important event or reaction: such events may not be immediately life-threatening or result in death or hospitalization but may jeopardize the subject or may require intervention to prevent one of the other outcomes constituting SAEs. These events had an onset date on or after the study drug start date and prior to the last exposure date of long-acting (LA) regimen period for the LA regimen period analysis. The long acting regimen period included participants who were randomized and received at least one dose of the complete LA study drug regimen (ie, SC LEN + Teropavimab + Zinlirvimab).
Measured: Day 1 up to Week 26
Secondary outcomes (24)
Primary Cohort: Percentage of Participants With Human Immunodeficiency Virus- 1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 26 as Determined by the US Food and Drug Administration (FDA)-Defined Snapshot Algorithm
The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 26 was analyzed using the 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. Week 26 window was between Days 176 and 224 (inclusive).
Measured: Week 26
Primary Cohort: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 26 as Determined by the US FDA-defined Snapshot Algorithm
The percentage of participants with HIV-1 RNA ≥ 50 copies/mL at Week 26 was analyzed using the snapshot algorithm, which defined a participant's virologic outcome and included participants a) who had the 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 AE or death and had the 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.
Week 26 window was between Days 176 and 224 (inclusive).
Measured: Week 26
Primary Cohort: Percentage of Participants With Positive Anti-Teropavimab Antibodies
Anti-teropavimab antibodies positive participants are participants with positive treatment-emergent anti-drug antibody.
Measured: Week 26
Primary Cohort: Percentage of Participants With Positive Anti-zinlirvimab Antibodies
Anti-zinlirvimab antibodies positive participants are participants with positive treatment-emergent anti-drug antibody.
Measured: Week 26
Primary Cohort: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 26
Measured: Baseline; Week 26
Primary Cohort: Number of Participants Who Develop Treatment-Emergent Resistance to LEN, Teropavimab, and Zinlirvimab
Participants in the Resistance Analysis Population analyzed for this outcome included any participant who had received 1 dose of study drug, maintained their study drug regimen, and met one of the following virologic failure criteria:
- Participants with HIV-1 RNA >/= 200 copies/mL on 2 consecutive visits
- Participants with HIV-1 RNA >/= 200 copies/mL at study discontinuation or Week 26.
Measured: Day 1 up to Week 26
Primary Cohort: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
TEAEs were those adverse events that began on or after the first dose date of study drug and prior to last exposure date of LA regimen from participants who prematurely discontinued study or completed study, or any adverse events led to premature study drug discontinuation.
Measured: Day 1 up to Week 26
Primary Cohort: Pharmacokinetic (PK) Parameter: AUC0-26 of Teropavimab
AUC0-26 is defined as the concentration of drug over time from Week zero to Week 26.
Measured: Predose and at End of Infusion (EOI) of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26
Primary Cohort: PK Parameter: AUC0-26 of Zinlirvimab
AUC0-26 is defined as the concentration of drug over time from Week zero to Week 26.
Measured: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26
Primary Cohort: PK Parameter: AUClast of Teropavimab
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Measured: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Primary Cohort: PK Parameter: AUClast of Zinlirvimab
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Measured: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Primary Cohort: PK Parameter: T1/2 of LEN
T1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Measured: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Primary Cohort: PK Parameter: T1/2 of Teropavimab
T1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Measured: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Primary Cohort: PK Parameter: T1/2 of Zinlirvimab
T1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Measured: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Primary Cohort: PK Parameter: Cmax of Teropavimab
Cmax is defined as the maximum observed concentration of drug.
Measured: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Primary Cohort: PK Parameter: Cmax of Zinlirvimab
Cmax is defined as the maximum observed concentration of drug.
Measured: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Primary Cohort: PK Parameter: Tmax of Teropavimab
Tmax is defined as the time (observed time point) of Cmax.
Measured: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Primary Cohort: PK Parameter: Tmax of Zinlirvimab
Tmax is defined as the time (observed time point) of Cmax.
Measured: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Primary Cohort: PK Parameter: Tlast of LEN
Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug).
Measured: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Primary Cohort: PK Parameter: Tlast of Teropavimab
Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug).
Measured: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Primary Cohort: PK Parameter: Tlast of Zinlirvimab
Tlast is defined as the time (observed time point) of Clast (the last observable concentration of drug).
Measured: Predose and at EOI of teropavimab and zinlirvimab on Day 1; Weeks 4, 8, 12, 16, 20, 24, 26, 38, 52, up to end of study (up to Week 55)
Primary Cohort: PK Parameter: C26week of LEN
C26week is the concentration at week 26.
Measured: Week 26
Primary Cohort: PK Parameter: C26week of Teropavimab
C26week is the concentration at week 26.
Measured: Week 26
Primary Cohort: PK Parameter: C26week of Zinlirvimab
C26week is the concentration at week 26.
Measured: Week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2021
- Study start8 Apr 2021
- Primary completion9 Jun 2022
- Study completion26 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for HIV-1 InfectionStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04811040
- Sponsor's protocol ID
- GS-US-536-5816
- Status last verified
- Dec 2024
- First submitted
- 19 Mar 2021
- Last updated
- 27 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Eron JJ, Cook PP, Mehrotra ML, Huang H, Caskey M, Crofoot GE, DeJesus E, Gorgos L, VanderVeen LA, Osiyemi OO, Brinson C, Collins SE. Lenacapavir Plus bNAbs for People with HIV and Susceptibility to Either Teropavimab or Zinlirvimab [Oral]. Conference on Retroviruses and Opportunistic Infections (CROI); 2024 3-6 March, Denver, CO.
Eron JJ, Little SJ, Crofoot G, Cook P, Ruane PJ, Jayaweera D, VanderVeen LA, DeJesus E, Zheng Y, Mills A, Huang H, Waldman SE, Ramgopal M, Gorgos L, Collins SE, Baeten JM, Caskey M. Safety of teropavimab and zinlirvimab with lenacapavir once every 6 months for HIV treatment: a phase 1b, randomised, proof-of-concept study. Lancet HIV. 2024 Mar;11(3):e146-e155. doi: 10.1016/S2352-3018(23)00293-X. Epub 2024 Jan 30.
PubMed 38307098Eron J, Little SJ, Crofoot G, Cook P, Ruane PJ, Jayaweera D, DeJesus E, Walkman SE, Mehrotra ML, VanderVeen L, Huang H, Collins S, Baeten J, Caskey M. Lenacapavir with bNAbs Teropavimab (GS-5423) and Zinlirvimab (GS-2872) Dosed Every 6 Months in People with HIV [Oral 193]. Conference on Retroviruses and Opportunistic Infections (CROI); 2023 19-22 February, Seattle, WA
Selzer L, VanderVeen LA, Parvangada A, Martin R, Collins SE, Mehrotra M, Callebaut C. Susceptibility Screening to bNAbs Teropavimab (GS-5423) and Zinlirvimab (GS-2872) in ART-Suppressed Participants [Poster]. Conference on Retroviruses and Opportunistic Infections (CROI); 2023 19-22 February; Seattle, WA
Selzer L, Demirdjian S, Falkard B, Li J, Martin R, Collins SE, Eron J, VanderVeen LA, Callebaut C. Resistance Analysis of Low-Level Virologic Rebound During HIV-1 Treatment With Lenacapavir and Broadly Neutralizing Antibodies Teropavimab and Zinlirvimab. J Infect Dis. 2026 Jan 17;233(1):e212-e220. doi: 10.1093/infdis/jiaf559.
PubMed 41205622Selzer L, VanderVeen LA, Parvangada A, Martin R, Collins SE, Mehrotra M, Callebaut C. Susceptibility Screening of HIV-1 Viruses to Broadly Neutralizing Antibodies, Teropavimab and Zinlirvimab, in People With HIV-1 Suppressed by Antiretroviral Therapy. J Acquir Immune Defic Syndr. 2025 Jan 1;98(1):64-71. doi: 10.1097/QAI.0000000000003528.
PubMed 39298557Eron JJ, Cook PP, Mehrotra ML, Huang H, Caskey M, Crofoot GE, Gorgos L, VanderVeen LA, Zheng Y, Collins SE, Osiyemi OO, Brinson C, DeJesus E. Lenacapavir Plus 2 Broadly Neutralizing Antibodies, Teropavimab and Zinlirvimab, for People With HIV-1 Highly Susceptible to Either Teropavimab or Zinlirvimab. J Infect Dis. 2025 Jul 11;231(6):1440-1444. doi: 10.1093/infdis/jiaf159.
PubMed 40176256