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)

NCT ID: NCT02411539

Last Updated: 2021-11-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-25
• Study Completion Date: 2016-09-29

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).

Detailed Description

Monoclonal antibodies (mAbs) have been developed as treatment for a variety of conditions including cancer, autoimmune disorders, and infections. mAbs may also be a potential treatment for people infected with HIV. The purpose of this study was to evaluate the safety and tolerability of an experimental human mAb, VRC-HIVMAB060-00-AB (VRC01), in HIV-infected adults receiving ART. Study researchers will also evaluate the effect of VRC01 on the number of infected cells containing unspliced HIV-1 transcripts in the blood in participants.

This study enrolled HIV-infected people 18 to 65 years old, who had been receiving ART for at least 2 years and who had a CD4+ count of 200 cells/mm^3 or greater. Participants were randomly assigned to Arm A or Arm B. Participants in Arm A received an intravenous (IV) infusion of VRC01 at Day 0 and Week 3 and an IV infusion of placebo (normal saline) at Weeks 6 and 9. Participants in Arm B received an IV infusion of placebo (normal saline) at Day 0 and Week 3 and an IV infusion of VRC01 at Weeks 6 and 9. Participants recorded their temperature and symptoms for 3 days after each infusion. Study visits occured at study entry (Day 0), and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 15, 18, and 30. Study visits included physical examinations, clinical assessments, and blood collection.

The primary safety outcome for this study was descriptive and assessed the occurrence of Grade ≥ 3 AEs including 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 study treatment to the end of study follow-up. Since this outcome is descriptive, no statistical significance testing was performed.

Conditions

HIV Infections

Keywords

HIV; VRC01

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Arm A: VRC01 followed by placebo

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

Group Type: EXPERIMENTAL

VRC01

Intervention Type: BIOLOGICAL

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

Placebo

Intervention Type: BIOLOGICAL

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

Arm B: placebo followed by VRC01

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

Group Type: EXPERIMENTAL

VRC01

Intervention Type: BIOLOGICAL

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

Placebo

Intervention Type: BIOLOGICAL

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

Interventions

VRC01

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

Intervention Type: BIOLOGICAL

Placebo

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

Intervention Type: BIOLOGICAL

Other Intervention Names

VRC-HIVMAB060-00-AB

Eligibility Criteria

Inclusion Criteria

• 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.
• All participants must have agreed not to participate in the conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the participant/partner must use at least one reliable form of contraception (condoms, with or without a spermicidal agent; a diaphragm or cervical cap with spermicide; an intrauterine device (IUD); or hormone-based contraceptive), while receiving study treatment and for 12 weeks after stopping study treatment
• Documentation of the availability of the following stored samples from the screening visit: peripheral blood mononuclear cell (PBMC) for CD4+ T-cell associated HIV-1 RNA, DNA assay and plasma for HIV-1 SCA. Sites must receive confirmation from the processing lab via phone, email, or fax, that specimens have been entered into the AIDS Clinical Trials Group (ACTG) Laboratory Data Management System (LDMS).

Exclusion Criteria

• 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

NETWORK

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sharon Riddler, MD, MPH

Role: STUDY_CHAIR

Pitt CRS

Locations

UCSD Antiviral Research Center CRS

San Diego, California, United States

University of Colorado Hospital CRS

Aurora, Colorado, United States

Northwestern University CRS

Chicago, Illinois, United States

Johns Hopkins University CRS

Baltimore, Maryland, United States

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, United States

Washington University Therapeutics (WT) CRS

St Louis, Missouri, United States

University of Rochester Adult HIV Therapeutic Strategies Network CRS

Rochester, New York, United States

Chapel Hill CRS

Chapel Hill, North Carolina, United States

Ohio State University CRS

Columbus, Ohio, United States

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, United States

Vanderbilt Therapeutics (VT) CRS

Nashville, Tennessee, United States

Houston AIDS Research Team CRS

Houston, Texas, United States

University of Washington AIDS CRS

Seattle, Washington, United States

Countries

Puerto Rico; United States

References

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.

Reference Type: DERIVED

PMID: 30364428 (View on PubMed)

Related Links

http://rsc.tech-res.com/safetyandpharmacovigilance/

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

Other Identifiers

12003

Identifier Type: REGISTRY

Identifier Source: secondary_id

UM1AI068636

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ACTG A5342

Identifier Type: -

Identifier Source: org_study_id