Safety and Therapeutic Efficacy of mAb VRC01 During ATI in Early Treatment During Acute HIV Infection

HIV Clinical Trial

Official title: Safety and Therapeutic Efficacy of the Broadly Neutralizing HIV-1 Specific Monoclonal Antibody VRC01 During Analytic Treatment Interruption in Patients Who Initiated Antiretroviral Therapy During Early Acute HIV Infection

Status Completed

Clinical Trial Summary

This is a placebo-controlled clinical trial of VRC01 administration and analytic treatment interruption (ATI) in adults who began antiretroviral therapy (ART) during early acute HIV infection (Fiebig stage I to III). Eligible volunteers will be randomized in a 3:1 ratio to either VRC01 or placebo, with randomization stratified by Fiebig stage. Volunteers who are receiving ART with a non-nucleoside reverse transcriptase inhibitor (NNRTI) will undergo 4 weeks of protease inhibitor (PI) substitution for their NNRTI prior to randomization. ATI will begin the day of the first dose of either VRC01 or placebo. Participants will be monitored closely for HIV viremia and other pre-defined criteria for ART resumption. Administration of the study agent (VRC01) every three weeks will be discontinued after 24 weeks or if ART is resumed, whichever occurs first. Volunteers who remain virally suppressed without laboratory or clinical indication for ART resumption at 24 weeks will continue intensive monitoring for ART resumption criteria for an additional 24 weeks, during which time no VRC01 or placebo will be administered.

Clinical Trial Description

The study agent, VRC-HIVMAB060-00-antibody (AB), was manufactured for the VRC by the Vaccine Pilot Plant operated by Leidos Biomedical Research, Inc, formerly SAIC-Frederick, Inc, Frederick, MD. Specific manufacturing information is included on the product vial labels and Certificates of Analysis and can be found in the Investigator's Brochure (IB). Quality Assurance (QA) lot release testing by the manufacturer and ongoing stability programs verify conformance to product specifications prior to use in clinical trials.

VRC-HIVMAB060-00-AB (VRC01) is a broadly neutralizing human monoclonal antibody (mAb) targeted against the HIV-1 CD4 binding site. It was developed by the VRC/NIAID/NIH. VRC01 is of the IgG1 subtype and is highly somatically mutated from its germ-line precursor. The heavy chain CDR3 region is 14 amino acids long, which is an average length relative to natural antibodies, and the glycosylation pattern is derived from its production in a Chinese Hamster Ovary (CHO) mammalian cell line.

This is a placebo-controlled clinical trial of VRC01 administration and ATI in adults who began ART during early acute HIV infection (Fiebig stage I to III). Eligible volunteers will be randomized in a 3:1 ratio to either VRC01 or placebo. Participants will undergo randomization stratified by Fiebig stage. Volunteers who are receiving ART with an NNRTI will undergo 4 weeks of PI substitution prior to randomization. ATI will begin the day of the first dose of either VRC01 or placebo. Participants will be monitored closely for HIV viremia and other pre-defined criteria for ART resumption. Administration of the study agent (VRC01) every 3 weeks will be discontinued after 24 weeks or at the time ART resumed, whichever occurs first. Volunteers who remain virally suppressed without laboratory or clinical indication for ART resumption at 24 weeks will continue intensive monitoring for ART resumption criteria for an additional 24 weeks, during which time no VRC01 or placebo will be administered. Clinical study visits will take place at the Thai Red Cross AIDS Research Centre, and the optional procedures may occur at the King Chulalongkorn Memorial Hospital.

This study will recruit 24 adults aged 20-50 years who were diagnosed during acute HIV infection (Fiebig stage I to III) and initiated on ART in Bangkok, Thailand. Participants will be recruited from protocol RV 254 (SEARCH 010, WRAIR 1494). This ongoing parent study cohort enrolls participants with documented acute HIV infection at the Thai Red Cross AIDS Research Center in Bangkok, Thailand. All participants in RV 254 are offered ART at the time of enrollment through a separately funded protocol.

Study agent:

VRC01 will be administered at a dose of 40 mg/kg intravenously every three weeks to participants assigned to the intervention arm of the trial for a total duration of 24 weeks or until ART resumption criteria are met, whichever comes first.

Placebo:

Normal saline (Sodium Chloride for Injection USP, 0.9%) will be administered intravenously every three weeks to participants assigned to the placebo arm of the trial for a total duration of 24 weeks or until ART resumption criteria are met, whichever comes first.

ANALYTIC TREATMENT INTERRUPTION (ATI) Analytic treatment interruption will begin on the day of administration of the first dose of either VRC01 or placebo. During the ATI, participants will be monitored closely for clinical and laboratory indications to resume ART. These criteria are designed to protect the subjects from clinical, immunological, or virological adverse effects during the ATI. ;

Related Conditions & MeSH terms

• HIV
• HIV Infections

• NCT number: NCT03036709
• Study type: Interventional
• Source: South East Asia Research Collaboration with Hawaii
• Status: Completed
• Phase: Phase 2
• Start date: August 2016
• Completion date: September 2019