A Study to Evaluate the Safety and Antiviral Activity of Two Human Monoclonal Antibodies (VRC07-523LS and PGT121.414.LS) During Analytic Treatment Interruption in Participants Living With HIV Who Initiated ART During Acute/Early HIV-1 Infection

NCT06987318 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: A5389
• Study Type: interventional
• Target: 40
• Locations: 3 countries
• Sites: 13

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and efficacy of combination broadly neutralizing antibodies (bNAbs), to induce HIV-1 control during analytic treatment interruption (ATI).

Conditions

HIV-1-infection

Keywords

Suppressive Antiretroviral Therapy; Acute HIV-1; Broadly neutralizing antibody; Antibodies; HIV; HIV antibody; HIV Broadly neutralizing antibody

Outcome Measures

Primary Outcomes (2)

• Number of participants experiencing a Grade ≥3 Adverse Event (AE) or Serious Adverse Events (SAE) that are related to VRC07-523LS or PGT121.414.LS

  Baseline through 36 weeks after the last dose of study treatment received

• Proportion of study participants experiencing viral suppression, defined as HIV-1 RNA <200 copies/mL and remaining off ART

  At 62 weeks after Step 1 entry

Secondary Outcomes (12)

• Change from Step 1 entry in cell-associated HIV-1 RNA/DNA ratio in total CD4+ cells

  Study entry through 72 weeks

• Change from Step 1 entry in low-level viremia measured by single copy assay (SCA)

  Study entry through 72 weeks

• Change from Step 1 entry in levels of intact proviral DNA in CD4+ T-cells

  Study entry through 72 weeks

• Change from Step 1 entry in levels of inducible infectious virus on CD4+ T-cells

  Study entry through 72 weeks

• Average number of weeks from ATI until meeting the virologic criteria for ART restart

  Week 2 through Week 72

Study Arms (2)

Arm A

EXPERIMENTAL

Biological: VRC07-523LS; Biological: PGT121.414.LS

Arm B

EXPERIMENTAL

Biological: VRC07-523LS; Biological: PGT121.414.LS

Interventions

VRC07-523LS BIOLOGICAL

Administered by Intravenous (IV) infusion at Week 0 and 12 weeks later

Arm A; Arm B

PGT121.414.LS BIOLOGICAL

Administered by IV infusion at Week 0

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability and willingness of participant to provide informed consent.
• Initiation of combination ART within 90 days of acute HIV diagnosis as defined by any of the criteria listed below:
• A negative HIV Ab or HIV Ag/Ab Combination Assay and a detectable HIV-1 RNA (qualitative or quantitative) or a subsequently positive Western blot (WB) or equivalent HIV-1 confirmatory assay (e.g. Geenius assay) if no positive HIV-1 RNA test was available.
• A positive HIV Ab or HIV Ag/Ab Combination Assay or p24 antigen test and a negative or indeterminate HIV confirmatory/differentiating test with a detectable HIV-1 RNA (qualitative or quantitative).
• A positive HIV Ab or HIV-1 RNA or p24 antigen and positive WB or Geenius HIV-1/HIV-2 Supplemental Assay that is negative for p31 band.
• Two different rapid HIV tests with discordant results followed by subsequently positive HIV serum antibody and/or HIV-1 RNA tests.
• A positive HIV antibody test according to standard criteria obtained within 60 days after an initial negative or indeterminate HIV antibody, antigen, or nucleic acid amplification.
• For women who are able to become pregnant, negative serum or urine pregnancy test within 48 hours prior to Step 1 entry.
• All study candidates must agree not to participate in an assisted conception process (e.g., sperm donation, intrauterine insemination, in vitro fertilization) from the screening visit until 12 weeks after the final study visit.
• Women who can become pregnant and are engaging in sexual activity that could lead to pregnancy must agree to use one highly effective method of contraception from Step 1 entry until 12 weeks after the final study visit.
• Willingness to use barrier protection (male or female) during sexual activity during ATI and through confirmed viral resuppression.
• Weight ≥50 kg and ≤150 kg at screening.
• On stable suppressive ART for at least 12 months prior to Step 1 entry. No known ART interruption for longer than 14 days within 12 months prior to Step 1 entry. No more than two known ART interruptions of a duration between 14 and 60 consecutive days since initiation of ART.
• ART regimens must contain a protease inhibitor (PI) or integrase strand transfer inhibitor (INSTI) as one of the active drugs in the ART regimen at the time of Step 1 entry.
• CD4+ cell count of \>450 cells/mL obtained within 60 days prior to Step 1 entry.

You may not qualify if:

• Breastfeeding or plans to become pregnant within the next 36 months.
• Known allergy/sensitivity or any hypersensitivity to components of study treatment or its formulation.
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• Receipt of any investigational vaccine within 6 months prior to Step 1 entry.
• Receipt of any vaccine within 14 days prior to Step 1 entry.
• Prior receipt of anti-HIV broadly neutralizing antibody therapy.
• Prior receipt of a latency-reversing agent (LRA), whether licensed or investigational, unless reviewed and approved by the study's CMC.
• AIDS-defining illness or opportunistic infection within 24 months prior to Step 1 entry.
• Any clinically significant acute or chronic medical condition (such as autoimmune diseases), other than HIV infection, that in the opinion of the investigator would preclude participation.
• Any history of an HIV-associated malignancy, including Kaposi's sarcoma and any type of lymphoma, or virus-associated cancers.
• History of progressive multifocal leukoencephalopathy (PML).
• Active or recent non-HIV-associated malignancy requiring systemic chemotherapy or surgery within 36 months prior to Step 1 entry or for whom such therapies are expected in the subsequent 12 months.
• Receipt of cabotegravir-LA intramuscular (IM) or rilpivirine-LA IM or lenacapavir (SQ) within 24 months prior to Step 1 entry.
• Resistance to one or more drugs in two or more ARV drug classes.
• History of systemic corticosteroids (long-term use), immunosuppressive anti-cancer or other immunosuppressive agents, interleukins, systemic interferons, systemic chemotherapy, or other medications considered significant by the investigator within the 6 months prior to Step 1 entry.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Monogram Biosciences: collaborator

Study Sites (13)

Alabama CRS

Birmingham, Alabama, 35222, United States

Location

UCSD Antiviral Research Center CRS

San Diego, California, 92103, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80045, United States

Location

The Ponce de Leon Center CRS

Atlanta, Georgia, 30308-2012, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, 02114, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27599-7215, United States

Location

Ohio State University CRS

Columbus, Ohio, 43210, United States

Location

Penn Therapeutics CRS

Philadelphia, Pennsylvania, 19104, United States

Location

Houston Advancing Research Team CRS

Houston, Texas, 77030, United States

Location

Instituto de Pesquisas em AIDS do Rio Grande do Sul - IPARGS CRS

Porto Alegre, Rio Grande do Sul, 91350-180, Brazil

Location

Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS

Rio de Janeiro, 21040-900, Brazil

Location

Barranco CRS

Lima, 15063, Peru

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Enrollment will be opened to Arm A first. Once Arm A enrollment is completed, enrollment to Arm B will be opened.

Study Record Dates

• First Submitted: April 25, 2025
• First Posted: May 23, 2025
• Study Start: February 15, 2026
• Primary Completion (Estimated): August 29, 2027
• Study Completion (Estimated): May 7, 2028
• Last Updated: November 12, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the ACTG (Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections) by NIH.
• Access Criteria: * With whom? * Researchers who provide a methodologically sound proposal for use of the data that is approved by the ACTG. * For what types of analyses? * To achieve aims in the proposal approved by the ACTG. * By what mechanism will data be made available? * Researchers may submit a request for access to data using the ACTG "Data Request" form at: https://submit.mis.s-3.net/ Researchers of approved proposals will need to sign an ACTG Data Use Agreement before receiving the data.

Locations

US (10); BR (2); PE (1)