A Clinical Trial of Combination HIV-Specific Broadly Neutralizing Monoclonal Antibodies Combined With ART Initiation During Acute HIV Infection to Induce HIV Remission

NCT05719441 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: A538838662
• Study Type: interventional
• Target: 48
• Locations: 3 countries
• Sites: 36

Brief Summary

A5388 is a phase II, two-arm, randomized, double-blind, placebo-controlled study that will enroll 48 antiretroviral therapy (ART)-naïve adults with acute HIV infection (AHI) in order to determine whether:

• Administration of combination HIV-specific broadly neutralizing antibody (bNAb) therapy in addition to ART during acute HIV infection (AHI) will be safe.
• Participants who receive combination bNAb therapy in addition to ART during AHI will be more likely to demonstrate a delay in time to HIV-1 RNA ≥1,000 copies/mL for 4 consecutive weeks compared to participants who receive placebo plus ART.
• Participants who receive combination bNAb therapy in addition to ART during AHI will demonstrate lower viral reservoirs and enhanced HIV-specific immunity compared to participants who receive placebo plus ART.

Conditions

Acute HIV Infection

Outcome Measures

Primary Outcomes (2)

• Occurrence of Grade ≥2 AE or SAE that are possibly, probably, or definitely related to the study bNAbs during Step 1

  Week 0 to end of Step 1

• Time from ART discontinuation to HIV-1 RNA ≥1,000 copies/mL for 4 consecutive weeks during Step 2

  From Step 2 entry through 24 weeks after ART interruption

Secondary Outcomes (13)

• Time from ART discontinuation to first documented HIV-1 RNA viral rebound of ≥50 copies/mL during Step 2

  From Step 2 entry through 24 weeks after ART interruption

• Time from ART discontinuation to first documented HIV-1 RNA viral rebound of ≥200 copies/mL during Step 2

  From Step 2 entry through 24 weeks after ART interruption

• Time from ART discontinuation to first documented HIV-1 RNA viral rebound of ≥1000 copies/mL during Step 2

  From Step 2 entry through 24 weeks after ART interruption

• Proportion of study participants who undergo ATI with HIV-1 RNA <200 copies/mL at 24 weeks after ART interruption, without indication of ART restart

  From Step 2 entry through 24 weeks after ART interruption

• Time from ART discontinuation to ART restart for an HIV-related reason (virologic, immunologic and clinical criteria) during Step 2

  From Step 2 entry through 24 weeks after ART interruption

Study Arms (2)

Arm 1: VRC07-523LS + PGT121.414.LS + ART

EXPERIMENTAL

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

Arm 2: Placebo + ART

PLACEBO COMPARATOR

Other: Placebo; Drug: ART

Interventions

VRC07-523LS BIOLOGICAL

10 mg/kg intravenous infusion over approximately 15 to 30 minutes once at entry

Also known as: VRC-HIVMAB075-00-AB

Arm 1: VRC07-523LS + PGT121.414.LS + ART

PGT121.414.LS BIOLOGICAL

5 mg/kg intravenous infusion over approximately 30 to 60 minutes once at entry

Also known as: VRC-HIVMAB0107-00-AB

Arm 1: VRC07-523LS + PGT121.414.LS + ART

Placebo OTHER

Sodium Chloride for Injection USP, 0.9%

Arm 2: Placebo + ART

ART DRUG

Bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablet orally once daily with or without food

Also known as: Biktarvy

Arm 1: VRC07-523LS + PGT121.414.LS + ART; Arm 2: Placebo + ART

Eligibility Criteria

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

You may qualify if:

• Step 1:
• Appropriate documentation from medical records of diagnosis of AHI prior to enrollment that includes one of the following:
• A detectable HIV-1 RNA within 28 days prior to study entry AND a non-reactive HIV-1 antibody within 7 days prior to entry; OR
• A detectable HIV-1 RNA or a reactive HIV-1 antibody within 28 days prior to study entry AND a negative/indeterminate Western Blot (WB) or negative/indeterminate Geenius HIV-1/HIV-2 Supplemental Assay within 7 days prior to entry; OR
• A documented non-reactive HIV-1 antibody or negative HIV-1 RNA within 90 days prior to study entry AND a documented reactive HIV-1 antibody or positive WB that is negative for p31 band or a positive Geenius HIV-1/HIV-2 Supplemental Assay that is negative for p31 band within 7 days prior to entry; OR
• ARCHITECT or GSCOMBO S/CO ≥10 within 7 days prior to entry AND a non-reactive HIV-1 antibody within 7 days prior to entry; OR
• ARCHITECT or GSCOMBO S/CO ≥1 within 7 days prior to entry AND a non-reactive HIV-1 antibody within 7 days prior to entry AND a known prior S/CO \<0.5 within 90 days prior to entry; OR
• ARCHITECT or GSCOMBO S/CO \>0.5 but \<10 within 7 days prior to entry AND a non-reactive HIV-1 antibody within 7 days prior to entry AND detectable HIV-1 RNA within 7 days prior to entry
• The following laboratory values obtained within 21 days prior to entry:
• Absolute neutrophil count (ANC) ˃1,000/mm3
• Hemoglobin:
• \>10 g/dL for cisgender men and transgender women
• \>9 g/dL for cisgender women and transgender men
• Platelet count ˃100,000/mm3
• Estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equation, with consideration for lower rates in special circumstances.

You may not qualify if:

• Step 1:
• Previous receipt of immunoglobulin (IgG) therapy.
• Previous receipt of humanized or human monoclonal antibody whether licensed or investigational (other than for the prevention and/or treatment of SARS-CoV-2/COVID-19).
• History of a severe allergic reaction with generalized urticaria, angioedema or anaphylaxis in the 2 years prior to enrollment.
• History of chronic urticaria requiring daily treatment.
• Receipt of investigational study agent within 28 days prior to enrollment.
• Past participation in an investigational study of a candidate HIV vaccine or immune prophylaxis for HIV-1 infection with receipt of active product or with receipt of active product or placebo and remains blinded to what they actually received.
• Active or recent non-HIV-associated malignancy requiring systemic chemotherapy or surgery in the preceding 36 months or for whom such therapies are expected in the subsequent 12 months.
• Use of any immunomodulatory medications within 6 months of study entry including systemic corticosteroids (long-term), immunosuppressants, anti-cancer, interleukins, systemic interferons, systemic chemotherapy, or other medications that the site investigator feels could have an immune modulatory effect.
• Use of ART for any reason, including pre- or post-exposure prophylaxis, within 60 days prior to study entry.
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• Known history of active Hepatitis B or Hepatitis C infection.
• Any acute, chronic, or recent and clinically significant medical condition that, in the opinion of the site investigator, would interfere with adherence to study requirements or jeopardize the safety or rights of the participant.
• History of or current clinical atherosclerotic cardiovascular disease (ASCVD) as defined by 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines, including a previous diagnosis of any of the following:
• Acute myocardial infarction

Sponsors & Collaborators

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

Study Sites (36)

31788, Alabama CRS

Birmingham, Alabama, 35222, United States

NOT YET RECRUITING

1201, University of Southern California CRS

Los Angeles, California, 90033-1079, United States

NOT YET RECRUITING

601, University of California, Los Angeles CARE Center CRS

Los Angeles, California, 90035, United States

NOT YET RECRUITING

701, UCSD Antiviral Research Center CRS

San Diego, California, 92103, United States

NOT YET RECRUITING

801, University of California, San Francisco HIV/AIDS CRS

San Francisco, California, 94110, United States

NOT YET RECRUITING

603, Harbor University of California Los Angeles Center CRS

Torrance, California, 90502, United States

NOT YET RECRUITING

6101, University of Colorado Hospital CRS

Aurora, Colorado, 80045, United States

RECRUITING

31791, Whitman-Walker Institute, Inc. CRS

Washington D.C., District of Columbia, 20005, United States

NOT YET RECRUITING

5802, The Ponce de Leon Center CRS

Atlanta, Georgia, 30308-2012, United States

RECRUITING

2701, Northwestern University CRS

Chicago, Illinois, 60611, United States

NOT YET RECRUITING

2702, Rush University CRS

Chicago, Illinois, 60612, United States

NOT YET RECRUITING

201, Johns Hopkins University CRS

Baltimore, Maryland, 21205, United States

NOT YET RECRUITING

101, Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, 02114, United States

NOT YET RECRUITING

107, Brigham and Women's Hospital Therapeutics (BWH TCRS) CRS

Boston, Massachusetts, 02115, United States

NOT YET RECRUITING

2101, Washington University Therapeutics (WT) CRS

St Louis, Missouri, 63110-1010, United States

NOT YET RECRUITING

31786, New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, 07103, United States

NOT YET RECRUITING

7804, Weill Cornell Chelsea CRS

New York, New York, 10010, United States

NOT YET RECRUITING

30329, Columbia Physicians & Surgeons (P&S) CRS

New York, New York, 10032-3732, United States

NOT YET RECRUITING

7803, Weill Cornell Uptown CRS

New York, New York, 10065, United States

NOT YET RECRUITING

31787, University of Rochester Adult HIV Therapeutic Strategies Network CRS

Rochester, New York, 14642, United States

NOT YET RECRUITING

3201, Chapel Hill CRS

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

NOT YET RECRUITING

3203, Greensboro CRS

Greensboro, North Carolina, 27401, United States

NOT YET RECRUITING

2401, Cincinnati CRS

Cincinnati, Ohio, 45267-0405, United States

NOT YET RECRUITING

2501, Case CRS

Cleveland, Ohio, 44106, United States

NOT YET RECRUITING

2301, Ohio State University CRS

Columbus, Ohio, 43210-1282, United States

RECRUITING

6201, Penn Therapeutics CRS

Philadelphia, Pennsylvania, 19104, United States

NOT YET RECRUITING

1001, University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

NOT YET RECRUITING

2951, The Miriam Hospital (TMH) CRS

Providence, Rhode Island, 02904, United States

NOT YET RECRUITING

3652, Vanderbilt Therapeutics (VT) CRS

Nashville, Tennessee, 37204, United States

NOT YET RECRUITING

31443, Trinity Health and Wellness Center CRS

Dallas, Texas, 75208, United States

NOT YET RECRUITING

31473, Houston AIDS Research Team CRS

Houston, Texas, 77030, United States

RECRUITING

1401, University of Washington Positive Research CRS

Seattle, Washington, 98104, United States

RECRUITING

12201, Hospital Nossa Senhora da Conceicao CRS

Porto Alegre, 91350-200, Brazil

NOT YET RECRUITING

12101, Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS

Rio de Janeiro, Brazil

RECRUITING

11302, San Miguel CRS

San Miguel, Lima region, 32, Peru

NOT YET RECRUITING

11301, Barranco CRS

Lima, 4, Peru

NOT YET RECRUITING

MeSH Terms

Interventions

bictegravir, emtricitabine, tenofovir alafenamide, drug combination

Study Officials

• Trevor Crowell, MD, PhD

  U.S. Military HIV Research Program CTU

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2023
• First Posted: February 9, 2023
• Study Start: August 19, 2024
• Primary Completion (Estimated): April 6, 2028
• Study Completion (Estimated): September 6, 2028
• Last Updated: April 21, 2026

Record last verified: 2026-04

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 AIDS Clinical Trials Group by NIH.
• Access Criteria: With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group. By what mechanism will data be made available? Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/aboutactg/templates-and-forms. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.

Locations

BR (2); US (32); PE (2)