Evaluating the Safety, Tolerability, and Effect of a Human Monoclonal Antibody (VRC01) on Markers of HIV Persistence in HIV-Infected Adults Receiving Antiretroviral Therapy (ART)

NCT02411539 | Completed Phase 1 Results DMC

• 3 other identifiers: ACTG A534212003UM1AI068636
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 13

Brief Summary

The purpose of this study was to evaluate the safety, tolerability, and effect of an experimental human monoclonal antibody (mAb), VRC-HIVMAB060-00-AB (VRC01), in adults infected with HIV who were receiving antiretroviral therapy (ART).

Conditions

HIV Infections

Keywords

HIV; VRC01

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experienced Grade 3 or Greater, Treatment Related, Adverse Event (AE)

  Refer to detailed description in the protocol section. Includes signs/symptoms, lab toxicities, and/or clinical events that are possibly, probably, or definitely related to study treatment (as judged by the core team, blinded to treatment arm) at any time from the initial dose of VRC01 to end of study follow-up. This analysis was primarily descriptive and no significance testing was performed.

  Measured from study treatment initiation to study discontinuation (study duration is 30 weeks)

• Change in Cell-associated HIV-1 RNA/DNA Ratio in Total CD4+ Cells

  Change from baseline (geometric average of screening and entry results) to week 6 in log10 transformed cell-associated HIV-1 RNA/DNA ratio in total CD4+ cells

  Screening, entry and week 6

Secondary Outcomes (34)

• Number of Participants With Premature Treatment Discontinuation, for Reasons Related to Study Treatment

  Measured from study treatment initiation to study treatment discontinuation (study treatment dispensed through week 12)

• Change in Cell-associated HIV-1 RNA/DNA Ratio in Total CD4+ Cells - Last Value Carried Forward (LVCF)

  Screening, entry, week 3 and week 6 (week 3 used as LVCF if necessary)

• Change in Cell-associated HIV-1 RNA/DNA Ratio in Total CD4+ Cells - Across Arms

  Screening, entry and weeks 6 and 12

• Cell-associated HIV-1 RNA in Total CD4+ Cells

  Measured at screening, entry, weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30

• Cell-associated HIV-1 DNA in Total CD4+ Cells

  Measured at screening, entry, weeks 1, 3, 4, 6, 7, 9, 10, 12, 15, 18 and 30

Study Arms (2)

Arm A: VRC01 followed by placebo

EXPERIMENTAL

Participants received an infusion of VRC01 at Day 0 and Week 3 and an infusion of placebo (normal saline) at Weeks 6 and 9.

Biological: VRC01; Biological: Placebo

Arm B: placebo followed by VRC01

EXPERIMENTAL

Participants received an infusion of placebo (normal saline) at Day 0 and Week 3 and an infusion of VRC01 at Weeks 6 and 9.

Biological: VRC01; Biological: Placebo

Interventions

VRC01 BIOLOGICAL

40 mg/kg of VRC01 administered as an intravenous infusion over about 30 to 60 minutes using a volumetric pump

Also known as: VRC-HIVMAB060-00-AB

Arm A: VRC01 followed by placebo; Arm B: placebo followed by VRC01

Placebo BIOLOGICAL

Normal saline administered as an intravenous infusion over about 30 to 60 minutes using a volumetric pump

Arm A: VRC01 followed by placebo; Arm B: placebo followed by VRC01

Eligibility Criteria

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

You may qualify if:

• HIV-1 infection, documented by any FDA-approved rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV or E/CIA tests, or by HIV-1 antigen, or plasma HIV-1 RNA assay. More information on this criterion is available in the protocol.
• Received continuous ART for at least 2 years (defined as no interruptions longer than 14 consecutive days) and with no changes in the components of the ART for at least 90 days prior to study entry
• CD4+ cell count greater than or equal to 200 cells/mm\^3 obtained within 60 days prior to study entry in a clinical laboratory improvement amendments (CLIA)-certified laboratory
• Plasma HIV-1 RNA below the limit of detection of the FDA-approved assays (limit of detection: 75, 50, 40 or 20 copies/mL) for greater than or equal to 2 years on ART. Participants must have had at least one documented HIV-1 RNA less than the limit of detection 12-24 months prior to study entry and at least one HIV-1 RNA less than the limit of detection within 12 months prior to study entry. All available HIV-1 RNA measurements must have been below the assay limit of detection during the 2 years prior to study entry except as allowed by the following note. NOTE: A single unconfirmed plasma HIV-1 RNA greater than the limit of detection but less than 200 copies/mL within 6-24 months was allowed if followed by a subsequent value below the limit of detection.
• Plasma HIV-1 RNA level of less than 40 copies/mL obtained by the Abbott Real-time HIV assay (m2000) or less than 20 copies/mL obtained by the Roche COBAS Taqman HIV-1 v2.0 assay within 60 days prior to entry
• The following laboratory values obtained within 60 days prior to entry by any U.S. laboratory that has a CLIA certification or its equivalent.
• Absolute neutrophil count (ANC) greater than or equal to 750 cells/mm\^3
• Hemoglobin greater than or equal to 11.0 g/dL for men and greater than or equal to 10.0 g/dL for women
• Platelet count greater than or equal to 100,000/mm\^3
• Creatinine clearance greater than or equal to 60 mL/min estimated by the Cockcroft-Gault equation. NOTE: A program for calculating creatinine clearance by the Cockcroft-Gault method is available on www.fstrf.org.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (SGPT) less than or equal to 2.0 times upper limit of normal (ULN)
• Hepatitis C virus (HCV) antibody negative result within 60 days prior to study entry or, if the HCV antibody result is positive, a negative HCV RNA result within 60 days prior to study entry
• Negative HBsAg result obtained within 60 days prior to study entry
• Ability and willingness of participant to provide informed consent
• Females of reproductive potential (women who have not been post-menopausal for at least 24 consecutive months, i.e., who have had menses within the preceding 24 months, or women who have not undergone surgical sterilization, specifically hysterectomy, or bilateral oophorectomy and/or bilateral salpingectomy), needed a negative serum or urine pregnancy test within 48 hours prior to study entry. NOTE: Acceptable documentation of hysterectomy and bilateral oophorectomy, bilateral salpingectomy, tubal micro-inserts, partner who has undergone vasectomy, and menopause is participant-reported history.

You may not qualify if:

• Previous receipt of humanized or human monoclonal antibody (licensed or investigational)
• Weight greater than 115 kg or less than 53 kg
• Acute or ongoing AIDS-defining illness within 60 days prior to study entry
• History of a severe allergic reaction with generalized urticarial, angioedema, or anaphylaxis within 2 years of study entry
• Currently breastfeeding or pregnant
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
• Acute or serious illness that, in the opinion of the site investigator, requires systemic treatment and/or hospitalization within 60 days prior to entry
• Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 60 days prior to study entry. NOTE: Participants receiving stable physiologic doses of glucocorticoids, defined as the equivalent of prednisone less than or equal to 10 mg/day, will not be excluded. Stable physiologic glucocorticoid doses should not be discontinued for the duration of the study. In addition, participants receiving inhaled or topical corticosteroids will not be excluded.
• Treatment for hepatitis C within 24 weeks of study entry
• Vaccinations within 7 days prior to the screening, pre-entry, or study entry visits. NOTE: Participants are encouraged to get routine vaccinations, such as seasonal influenza vaccine more than 7 days prior to screening or between screening and pre-entry visits (outside of the 7-day window above).
• Initiation of ART during acute HIV-1 infection (as determined by the site investigator by history and/or available medical records)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: collaborator

Study Sites (13)

UCSD Antiviral Research Center CRS

San Diego, California, 92103, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80045, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Johns Hopkins University CRS

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, 02114, United States

Location

Washington University Therapeutics (WT) CRS

St Louis, Missouri, 63110-1010, United States

Location

University of Rochester Adult HIV Therapeutic Strategies Network CRS

Rochester, New York, 14642, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27599, United States

Location

Ohio State University CRS

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt Therapeutics (VT) CRS

Nashville, Tennessee, 37204, United States

Location

Houston AIDS Research Team CRS

Houston, Texas, 77030, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98104-9929, United States

Location

Related Publications (1)

• Riddler SA, Zheng L, Durand CM, Ritz J, Koup RA, Ledgerwood J, Bailer RT, Koletar SL, Eron JJ, Keefer MC, Macatangay BJC, Cyktor JC, Mellors JW; AIDS Clinical Trials Group A5342 Protocol Team. Randomized Clinical Trial to Assess the Impact of the Broadly Neutralizing HIV-1 Monoclonal Antibody VRC01 on HIV-1 Persistence in Individuals on Effective ART. Open Forum Infect Dis. 2018 Oct 20;5(10):ofy242. doi: 10.1093/ofid/ofy242. eCollection 2018 Oct.

  PMID: 30364428 DERIVED

Related Links

• To grade diagnoses, signs and symptoms, and laboratory results, sites referred to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.0, November 2014

MeSH Terms

Conditions

HIV Infections

Interventions

VRC01 monoclonal antibody

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• Sharon Riddler, MD, MPH

  Pitt CRS

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2015
• First Posted: April 8, 2015
• Study Start: August 25, 2015
• Primary Completion: April 15, 2016
• Study Completion: September 29, 2016
• Last Updated: November 5, 2021
• Results First Posted: July 31, 2017

Record last verified: 2018-06

Locations

US (13)