Study of VRC07-523LS, CAP256V2LS, and Vesatolimod, in Early Antiretroviral-treated HIV-1 Clade C-infected Women

A Phase 2a Study to Evaluate the Safety and Tolerability of a Regimen of Dual Anti-HIV Envelope Antibodies, VRC07-523LS and CAP256V2LS, in a Sequential Regimen With a TLR7 Agonist, Vesatolimod, in Early Antiretroviral-Treated HIV-1 Clade C-Infected Women

The goals of this clinical study are to learn more about the study drugs, VRC07-523LS, CAP256V2LS, and vesatolimod (VES) and how safe it is in women that have HIV and are on antiretroviral therapy (ART).

Study Overview

• Status: Completed
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: Vesatolimod; Biological: VRC07523LS; Biological: CAP256V2LS

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• South Africa
  • Umlazi, South Africa, 4066
    • FRESH Clinical Research Site: Females Rising through Education, Support and Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Age ≥ 18 years
• Females recruited from the Females Rising through Education, Support, and Health (FRESH) acute human immunodeficiency virus (HIV) infection cohort.
• Plasma human immunodeficiency -1 (HIV-1) ribonucleic acid (RNA) levels < 50 copies/mL at the screening visit.
• On antiretroviral (ART) regimen for ≥ 12 consecutive months prior to the screening visit.

• Have all the following laboratory values at the screening visit:

  • Hemoglobin ≥ 10.0 g/dL
  • White blood cells ≥ 2500 cells/μL
  • Platelets ≥ 125,000/mL
  • Absolute neutrophil counts ≥ 1000 cells/μL
  • Cluster of differentiation (CD)4+ T cell count ≥ 500 cells/μL
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin ≤ 2 × upper limit of normal (ULN)
  • Creatinine clearance ≥ 60 mL/min
• Women of childbearing potential to have documentation of agreement to follow study contraceptive requirements.
• Documented plasma HIV-1 RNA < 50 copies/mL for 12 consecutive months prior to the screening visit.
• In the judgment of the investigator, be in good general health.
• Documented history of viral sensitivity to VRC07-523LS or CAP256V2LS at the screening visit.

Key Exclusion Criteria:

• Have poor venous access that limits phlebotomy.
• Positive serum pregnancy test.
• Nursing participants.

• Females with coinfection and/or immunosuppression as described below:

  • Autoimmune disease requiring ongoing immunosuppression
  • Evidence of chronic hepatitis B virus (HBV) infection
  • Evidence of current hepatitis C virus (HCV) infection
  • Documented history of pre-ART CD4+ T cell count nadir < 200 cells/μL
  • History of opportunistic illness indicative of Stage 3 HIV
  • Acute febrile illness within 4 weeks prior to the first dose
• Have current alcohol or substance abuse judged by the investigator to potentially interfere with individual's compliance or individual's safety.
• Have been treated with systemic steroids, immunosuppressant therapies, or chemotherapeutic agents within 3 months prior to screening or are expected to receive these agents during the study.
• Have previous or current receipt of humanized or human monoclonal antibody (mAbs), or polyclonal immunoglobulin.
• Have previous history of an antidrug antibodies response to a therapeutic agent.
• Have previous receipt of an HIV vaccine.
• Received any vaccine or immunomodulatory medication within 4 weeks prior to screening.

• Have a history of any of the following:

  • Significant serious skin disease
  • Significant drug sensitivity or drug allergy
  • Known hypersensitivity to the study drugs, metabolites, or formulation excipients
  • Previous or current history of bleeding disorder, platelet disorder including unexplained acute or chronic thrombocytopenia
  • Autoimmune diseases including type 1 diabetes mellitus
• Have current Class C acquired immunodeficiency syndrome (AIDS)-defining condition.
• Have any serious or active medical or psychiatric illness that would interfere with participants treatment, assessment, or compliance with the protocol.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: VRC07523LS + CAP256V2LS + Vesatolimod (VES); In Period 1 (Days 0-28), participants will receive ART through Period. On Days 0 & 14, participants will be administered VES 6mg orally and on Day 28, participants will be administered VES either 6 or 8mg orally. VRC07-523LS & CAP256V2LS 20mg/kg will be administered intravenously on Day 7. In Period 2 (Days 29-133 or until ART restart), participants will discontinue ART at Day 35 and remain off ART until reaching ART restart criteria. Participants will receive VES 6 or 8mg orally every 2 weeks from Day 29 or until plasma HIV-1 RNA is >=5000 copies/mL. In Period 3, (Days 134-336 or until ART restart), participants will continue ATI and no study treatment will be administered. In Period 4, (Days 337-413) participants who have not met ART restart criteria by Day 337 may choose to restart ART (Period 4a) or may choose to continue ATI until end of study (Period 4B). Any participants who meet ART restart criteria before the end of the study will remain in follow-up on ART (Period 4A).

Drug: Vesatolimod; Administered orally; Other Names: GS-9620; Biological: VRC07523LS; Administered intravenously; Biological: CAP256V2LS; Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)	An AE is any untoward medical occurrence in a clinical study participant administered a study drug that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not the AE is considered related to the study drug. TEAE was defined as any AE that began on or after the study drug start date and no later than last exposure date after permanent discontinuation of study drug, or led to premature study drug discontinuation.	Up to 61.1 weeks
Percentage of Participants Experiencing Treatment-emergent Graded Laboratory Abnormalities	A treatment-emergent laboratory abnormality was defined as an increase of at least 1 toxicity grade from baseline at any time postbaseline up to and including the last exposure date after permanent discontinuation of study drug. For maximum postbaseline toxicity grade, the most severe graded abnormality from all tests was counted for each participant. The severity grades were defined by Gilead Grading Scale for Severity of Adverse Events and Laboratory Abnormalities, Antiviral Toxicity Grading Scale, Version 01 April 2015. The CTCAE v5 grading scale was used to grade AEs determined to be cytokine release syndrome and infusion-related reactions. The grading for both scales are as follows: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-Threatening, Grade 5 = Death.	Up to 61.1 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Viral Rebound (Confirmed ≥ 50 Copies/mL and ≥ 200 Copies/mL) Following ATI	Virologic rebound is defined as at any visit a rebound in HIV-1 RNA to ≥ 50 copies/mL or ≥ 200 copies/mL, which is subsequently confirmed at the following scheduled or unscheduled visit. Time to rebound (in weeks) = (date of rebound or censoring date - ATI start date + 1) / 7.	Up to 56 weeks
Change in Plasma Viral Load Set-point Following ATI	Change in plasma viral load set-point between pre-ART value and prior to ART reinitiation following ATI was summarized. The pre-ART set point value is the HIV-RNA load count prior to start of initial ARV treatment recorded in the clinical database.	Pre-ART (Screening) and prior to ART reinitiation following ATI (Up to 56 weeks)
Change From Baseline of Viral Load at the End of ATI	Baseline value was the last available value collected on or prior to first dose of study drug.	Up to 48 weeks
Time to ART Resumption Following ATI	Time to ART resumption (in weeks) = (date of restart ART after ATI period start or censoring date - ATI start date + 1) / 7.	Up to 56 weeks
Pharmacokinetic (PK) Parameter of VES: Cmax	Cmax is defined as maximum observed concentration of drug.	Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose
PK Parameter of VES: Tmax	Tmax is defined as time (observed time point) of Cmax.	Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose
PK Parameter of VES: Clast	Clast is defined as last observed quantifiable concentration of the drug.	Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose
PK Parameter of VES: Tlast	Tlast is defined as time (observed time point) of Clast.	Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose
PK Parameter of VES: AUCinf	AUCinf is defined as area under the concentration versus time curve extrapolated to infinite time, calculated as AUClast + (Clast/λz).	Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose
PK Parameter of VES: AUClast	AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration.	Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose
PK Parameter of VES: AUCexp	AUCexp is defined as AUC extrapolated between AUClast and AUCinf.	Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose
PK Parameter of VES: t1/2	t1/2 is defined as estimate of the terminal elimination half-life of the drug, calculated by dividing the natural log of 2 by the terminal elimination rate constant (λz).	Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose
PK Parameter of VES: CL/F	CL/F is defined as apparent clearance following extravascular administration.	Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose
PK Parameter of VES: Vz/F	Vz/F is defined as apparent volume of distribution during the terminal phase following extravascular administration.	Day 1: Predose (≤ 5 minutes prior to dosing), 1, 2, 4, 8, 12, 24, and 48 hours postdose
PK Parameter of VRC07-523LS: Cmax	Cmax is defined as maximum observed concentration of drug.	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of VRC07-523LS: Tmax	Tmax is defined as time (observed time point) of Cmax.	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of VRC07-523LS: Clast	Clast is defined as last observed quantifiable concentration of the drug.	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of VRC07-523LS: Tlast	Tlast is defined as time (observed time point) of Clast.	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of VRC07-523LS: AUCinf	AUCinf is defined as area under the concentration versus time curve extrapolated to infinite time, calculated as AUClast + (Clast/λz).	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of VRC07-523LS: AUClast	AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration.	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of VRC07-523LS: AUCexp	AUCexp is defined as AUC extrapolated between AUClast and AUCinf.	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of VRC07-523LS: t1/2	t1/2 is defined as estimate of the terminal elimination half-life of the drug, calculated by dividing the natural log of 2 by the terminal elimination rate constant (λz).	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of VRC07-523LS: Clearance (CL)	CL is defined as clearance following intravenous administration.	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of VRC07-523LS: Vss	Vss is defined as the volume of distribution at steady-state following intravenous administration.	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of VRC07-523LS: Vz	Vz is defined as volume of distribution of the drug during the terminal phase after intravenous administration.	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of CAP256V2LS: Cmax	Cmax is defined as maximum observed concentration of drug.	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of CAP256V2LS: Tmax	Tmax is defined as time (observed time point) of Cmax.	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of CAP256V2LS: Clast	Clast is defined as last observed quantifiable concentration of the drug.	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of CAP256V2LS: Tlast	Tlast is defined as time (observed time point) of Clast.	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of CAP256V2LS: AUCinf	AUCinf is defined as area under the concentration versus time curve extrapolated to infinite time, calculated as AUClast + (Clast/λz).	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of CAP256V2LS: AUClast	AUClast is defined as area under the concentration versus time curve from time zero to the last quantifiable concentration.	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of CAP256V2LS: AUCexp	AUCexp is defined as AUC extrapolated between AUClast and AUCinf.	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of CAP256V2LS: t1/2	t1/2 is defined as estimate of the terminal elimination half-life of the drug, calculated by dividing the natural log of 2 by the terminal elimination rate constant (λz).	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of CAP256V2LS: CL	CL is defined as clearance following intravenous administration.	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of CAP256V2LS: Vz	Vz is defined as volume of distribution of the drug during the terminal phase after intravenous administration.	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
PK Parameter of CAP256V2LS: Vss	Vss is defined as the volume of distribution at steady-state after intravenous administration.	Day 7: Predose (0 hours), end of infusion, 1, 2, 4, and 8 hours after end of infusion, and then anytime on Days 8, 9, 14, 21, 28, 56, 84, 112, 133, 161, 189, 217, 245, 273, 301, 329, 343, 371, and 413
Percentage of Participants With Treatment-emergent Positive Anti-VRC07-523LS Antibodies		Prebaseline (Day -13) up to Day 413
Percentage of Participants With Treatment-emergent Positive Anti-CAP256V2LS Antibodies		Prebaseline (Day -13) up to Day 413

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

General Publications

• Dong K, Asari V, Govender V, et al. Evaluation of 2 bNAbs plus vesatolimod in early-treated South African women with HIV-1 during ATI [CROI abstract 105]. Top Antivir Med. 2025;33:14
• Omange RW, Zhang L, Reddy K, et al. Presence of protective human leukocyte antigen class I and II is associated with improved analytical treatment interruption outcomes in a trial of vesatolimod and broadly neutralizing antibodies in South African women with early-treated clade C HIV-1. Presented at the Keystone HIV Cure: Antiretroviral Therapy-Free Control of HIV Infection Symposium; April 7-10, 2025; Durban, South Africa. Poster 2014.
• Dong K, SenGupta D, Gama L, et al. First HIV cure interventional trial in Africa with collaboration between academia, government, and industry. Presented at the 13th International AIDS Society (IAS) Conference on HIV Science; July 13-17, 2025; Kigali, Rwanda. ePoster EP1003.
• Cai Y, Zhang L, Omange RW, et al. Vesatolimod pharmacodynamic responses in a trial of vesatolimod and broadly neutralizing antibodies in early-treated South African women with clade C HIV-1. Presented at the 13th International AIDS Society (IAS) Conference on HIV Science; July 13-17, 2025; Kigali, Rwanda. Poster WEPEB018.

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2022
• Primary Completion (Actual): January 16, 2025
• Study Completion (Actual): January 16, 2025

Study Registration Dates

• First Submitted: March 7, 2022
• First Submitted That Met QC Criteria: March 7, 2022
• First Posted (Actual): March 16, 2022

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: December 24, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiviral Agents; vesatolimod
• Other Study ID Numbers: GS-US-382-5445; DOH-27-082021-8379 (Other Identifier: South African National Clinical Trials Registry)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes