HIV-1-infectionPhase 2NCT05281510
Study of VRC07-523LS, CAP256V2LS, and Vesatolimod, in Early Antiretroviral-treated HIV-1 Clade C-infected Women
A Phase 2 study testing Vesatolimod, VRC07523LS and CAP256V2LS in people with HIV-1-infection, run by Gilead Sciences at 1 site in South Africa.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- HIV-1-infection
- What is being tested?
- Vesatolimod, VRC07523LS and CAP256V2LS
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteSouth Africa
- Study dates
- 9 Jun 2022to 16 Jan 2025
- Phase
- Phase 2
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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
South Africa1 site
FRESH Clinical Research Site: Females Rising through Education, Support and Health
Umlazi, 4066
About this study
Official title: 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).
- Conditions
- HIV-1-infection
- Being tested
- Vesatolimod, VRC07523LS, CAP256V2LS
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VesatolimodDrug
Also called GS-9620
Administered orally
VRC07523LSBiological
Administered intravenously
CAP256V2LSBiological
Administered intravenously
| Study group | Role | What they receive |
|---|---|---|
| VRC07523LS + CAP256V2LS + Vesatolimod (VES) | Experimental | 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). Receives: Drug: Vesatolimod; Biological: VRC07523LS; Biological: CAP256V2LS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to 61.1 weeks
Secondary outcomes (38)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 56 weeks
Pharmacokinetic (PK) Parameter of VES: Cmax
Cmax is defined as maximum observed concentration of drug.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: Prebaseline (Day -13) up to Day 413
Percentage of Participants With Treatment-emergent Positive Anti-CAP256V2LS Antibodies
Measured: Prebaseline (Day -13) up to Day 413
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2022
- Study start9 Jun 2022
- Primary completion16 Jan 2025
- Study completion16 Jan 2025
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 (6)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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 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
- NCT05281510
- Sponsor's protocol ID
- GS-US-382-5445
- Other IDs
- DOH-27-082021-8379
- Status last verified
- Dec 2025
- First submitted
- 7 Mar 2022
- Last updated
- 16 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
Ahmed A, Hill M, Dong KL, Ngcobo MW, Zulu A, Langa N, Maphalala L, Pillay V, Mthembu M, Tran W, Lau R, Stockman JK, Ndung'u T, Dube K. Stress and Coping During an HIV Cure-Related Trial with an Analytical Treatment Interruption: A Qualitative Assessment of the Experiences of Young Women in Durban, South Africa. J Int Assoc Provid AIDS Care. 2026 Jan-Dec;25:23259582261423985. doi: 10.1177/23259582261423985. Epub 2026 Feb 13.
PubMed 41685863Ahmed A, Dong KL, Hussain M, Ngcobo MW, Langa N, Zulu A, Maphalala L, Pillay V, Mthembu M, Wan F, Tran W, Lau R, Stockman JK, Ndung'u T, Dube K. Psychological Impact of Analytical Treatment Interruption on Young Women Enrolled in an HIV Cure-Related Clinical Trial in Durban, South Africa. AIDS Res Hum Retroviruses. 2026 Mar;42(3):109-116. doi: 10.1177/08892229251405807. Epub 2026 Jan 2.
PubMed 41449969