Evaluating the Safety and Efficacy of the VRC01 Antibody in Reducing Acquisition of HIV-1 Infection Among Men and Transgender Persons Who Have Sex With Men

NCT02716675 | Completed Phase 2 Results DMC

• 2 other identifiers: HVTN 704/HPTN 08530095
• Study Type: interventional
• Target: 2,699
• Locations: 4 countries
• Sites: 26

Brief Summary

This study will evaluate the safety and efficacy of the human monoclonal antibody (mAb) VRC-HIVMAB060-00-AB (VRC01) in preventing HIV-1 infection among men and transgender (TG) persons who have sex with men, in North America, South America, and Switzerland.

Conditions

HIV Infections

Keywords

HIV-1 Infections

Outcome Measures

Primary Outcomes (12)

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented

  Measured through 3 days after each infusion at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.

• Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Erythema and/or Induration

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented

  Measured through 3 days after each infusion at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.

• Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The following symptoms are considered as systemic reactogenicity if the onset date was within the periods of assessment specified in the protocol: malaise and/or fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and body temperature. The item Max. Systemic Symptoms is the maximum of the individual systemic reactogenicities excluding body temperature for a participant.

  Measured through 3 days after each infusion at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.

• Chemistry and Hematology Laboratory Measures - Alanine Aminotransferase (ALT)

  For each local laboratory measure, summary statistics are presented by treatment group and timepoint.

  Measured at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.

• Chemistry and Hematology Laboratory Measures - Creatinine

  For each local laboratory measure, summary statistics are presented by treatment group and timepoint.

  Measured at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.

• Chemistry and Hematology Laboratory Measures - Hemoglobin

  For each local laboratory measure, summary statistics are presented by treatment group and timepoint.

  Measured at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.

• Chemistry and Hematology Laboratory Measures - Lymphocyte Count, Neutrophil Count

  For each local laboratory measure, summary statistics are presented by treatment group and timepoint.

  Measured at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.

• Chemistry and Hematology Laboratory Measures - Platelets, White Blood Cells (WBC)

  For each local laboratory measure, summary statistics are presented by treatment group and timepoint.

  Measured at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, 72.

• Chemistry and Hematology Laboratory Measures Meeting Grade 3 AE Criteria or Above

  The number (percentage) of participants with chemistry and hematology laboratory measures meeting grade 3 AE criteria or above as specified in the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\] is tabulated by treatment group and timepoint. Excludes measures taken prior to exposure to study product at Week 0/Infusion 1.

  Measured at Weeks 8, 16, 24, 32, 40, 48, 56, 64, 72.

• Number of Participants With Early Infusion Discontinuation and Reasons for Discontinuation

  The number (percentage) of participants with early permanent discontinuation of infusions and their reason for discontinuation is summarized by treatment group. Includes all discontinuations documented on a study case report form.

  Measured through Week 72 (the last infusion visit).

• Incidence Rate of Early Infusion Discontinuation

  Incidence rate (95% CI) of early infusion discontinuation per 100 person years. Includes discontinuations documented on a study case report form and operational discontinuations defined as 20 consecutive weeks without participant contact. Discontinuations due to pregnancy, death, or HIV-1 infection are right-censored.

  Measured through Week 72 (the last infusion visit).

• Number of Participants With Documented HIV-1 Infection by the Week 80 Visit

  Prevention efficacy (PE) is measured as 1 minus the ratio (VRC01:control) of cumulative incidences of HIV-1 infection diagnosis between enrollment and the week 80 visit for assessment of the primary efficacy end point. Cumulative incidence was estimated with the Nelson-Aalen estimator for the cumulative hazard function, with stratification according to VRC01 dose and trial.

  Measured through Week 80.

Secondary Outcomes (3)

• Serum Concentration of VRC01 in Participants Assigned to Receive the mAb

  Day 61 (5 days post infusion #2), Midpoint (4-weeks post infusion visits): Weeks 4, 12, 16, 28, 36, 44, 52, 60, 68, 76 and Trough (infusion visits): Pre dose at Weeks 0 (study entry), 8, 16, 24, 32, 40, 48, 56, 64, and 72.

• VRC01 Clinical Lot Neutralization of Founder Viruses (IC80)

  Measured through Week 80.

• VRC01 Serum Neutralization of Autologous Founder Viruses (ID50, ID80)

  First RNA+ Sample detected from baseline up to Week 104.

Study Arms (3)

Group 1: Low-Dose VRC01

EXPERIMENTAL

Participants will receive an intravenous (IV) infusion of 10 mg/kg of VRC01 over about 15 to 60 minutes at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, and 72.

Biological: VRC01

Group 2: High-Dose VRC01

EXPERIMENTAL

Participants will receive an IV infusion of 30 mg/kg of VRC01 over about 15 to 60 minutes at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, and 72.

Biological: VRC01

Group 3: VRC01 Placebo

PLACEBO COMPARATOR

Participants will receive an IV infusion of placebo for VRC01 over about 15 to 60 minutes at Weeks 0, 8, 16, 24, 32, 40, 48, 56, 64, and 72.

Biological: Placebo for VRC01

Interventions

VRC01 BIOLOGICAL

Administered by IV infusion; total dose will vary based on participant's weight

Also known as: Human monoclonal antibody (mAb) VRC-HIVMAB060-00-AB

Group 1: Low-Dose VRC01; Group 2: High-Dose VRC01

Placebo for VRC01 BIOLOGICAL

Sodium Chloride for Injection USP, 0.9%; administered by IV infusion

Group 3: VRC01 Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• General and Demographic Criteria
• Age of 18 to 50 years
• Access to a participating clinical research site (CRS) and willingness to be followed for the planned duration of the study
• Ability and willingness to provide informed consent
• Assessment of understanding: volunteer demonstrates understanding of this study and completes a questionnaire prior to first infusion with verbal demonstration of understanding of all questionnaire items answered incorrectly
• Agrees not to enroll in another study of an investigational research agent for the duration of the participant's trial participation
• Good general health as shown by medical history, physical exam, and screening laboratory tests
• HIV-Related Criteria
• Willingness to receive HIV test results
• Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling
• Persons born Male or identifying as Transgender (TG) (male-to-female or female-to-male, see HVTN 704/HPTN 085 SSP) who, in the 6 months prior to randomization, experienced 1 or both of the following HIV risk criteria:
• Condomless anal intercourse with 1 or more male or transgender partner(s)
• Anal intercourse with 2 or more male or transgender partners
• Male-to-female and female-to-male TG volunteers are eligible. Receipt of hormonal therapy does not make a TG volunteer ineligible.
• Volunteers who have been in a mutually monogamous relationship with an HIV-1 seronegative partner for greater than 1 year are excluded.

You may not qualify if:

• General
• Investigational research agents received within 30 days before first infusion
• Body mass index (BMI) greater than or equal to 40
• Pregnant or breastfeeding
• Any reactive, indeterminate, or positive HIV test, even if subsequent testing indicates that the individual is not HIV infected, except as permitted by the HVTN 704/HPTN 085 Protocol Safety Review Team (PSRT).
• Vaccines
• HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 704/HPTN 085 PSRT will determine eligibility on a case-by-case basis.
• Immune System
• Serious adverse reactions to VRC01 formulation components such as sodium citrate, sodium chloride, and L-arginine hydrochloride, including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain.
• Autoimmune disease, including Type I diabetes mellitus (Not excluded from participation: Volunteer with mild, stable and uncomplicated autoimmune disease that does not require consistent immunosuppressive medication and that, in the judgment of the site investigator, is likely not subject to exacerbation and likely not to complicate reactogenicity and AE assessments)
• Immunodeficiency syndrome
• Clinically Significant Medical Conditions
• Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:
• Any contraindication to repeated infusions or blood draws, including inability to establish venous access;
• A condition that requires active medical intervention or monitoring to avert grave danger to the volunteer's health or well-being during the study period; or

Sponsors & Collaborators

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

Study Sites (26)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

UCLA Vine Street Clinic CRS

Los Angeles, California, 90024, United States

Location

Bridge HIV CRS

San Francisco, California, 94143, United States

Location

George Washington Univ. CRS

Washington D.C., District of Columbia, 20006, United States

Location

The Ponce de Leon Center CRS

Atlanta, Georgia, 30308-2012, United States

Location

The Hope Clinic of the Emory Vaccine Center CRS

Decatur, Georgia, 30030, United States

Location

Brigham and Women's Hospital Vaccine CRS (BWH VCRS)

Boston, Massachusetts, 02115-6110, United States

Location

Fenway Health (FH) CRS

Boston, Massachusetts, 02215-4302, United States

Location

New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, 07103, United States

Location

Harlem Prevention Center CRS

New York, New York, 10027, United States

Location

Columbia P&S CRS

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

Location

New York Blood Center CRS

New York, New York, 10065, United States

Location

University of Rochester Vaccines to Prevent HIV Infection CRS

Rochester, New York, 14642, United States

Location

Bronx Prevention Research Center CRS

The Bronx, New York, 10451, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27599, United States

Location

Case Clinical Research Site

Cleveland, Ohio, 44106, United States

Location

Penn Prevention CRS

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt Vaccine (VV) CRS

Nashville, Tennessee, 37232-2582, United States

Location

Seattle Vaccine and Prevention CRS

Seattle, Washington, 98109-1024, United States

Location

Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS

Rio de Janeiro, 21040-360, Brazil

Location

ACSA CRS

Iquitos, Maynas, 1, Peru

Location

CITBM - UNIDEC, Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales CRS

Bellavista, Provincia Constitucional del Callao, 15081, Peru

Location

Barranco CRS

Lima, 04, Peru

Location

San Miguel CRS

Lima, 32, Peru

Location

Via Libre CRS

Lima, Lima 01, Peru

Location

Lausanne Vaccine and Immunotherapy Center CRS

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Related Publications (7)

• Edupuganti S, Mgodi N, Karuna ST, Andrew P, Rudnicki E, Kochar N, deCamp A, De La Grecca R, Anderson M, Karg C, Tindale I, Greene E, Broder GB, Lucas J, Hural J, Gallardo-Cartagena JA, Gonzales P, Frank I, Sobieszczyk M, Gomez Lorenzo MM, Burns D, Anderson PL, Miner MD, Ledgerwood J, Mascola JR, Gilbert PB, Cohen MS, Corey L; HVTN 704/HPTN 085 study group. Feasibility and Successful Enrollment in a Proof-of-Concept HIV Prevention Trial of VRC01, a Broadly Neutralizing HIV-1 Monoclonal Antibody. J Acquir Immune Defic Syndr. 2021 May 1;87(1):671-679. doi: 10.1097/QAI.0000000000002639.

  PMID: 33587505 RESULT

• Mgodi NM, Takuva S, Edupuganti S, Karuna S, Andrew P, Lazarus E, Garnett P, Shava E, Mukwekwerere PG, Kochar N, Marshall K, Rudnicki E, Juraska M, Anderson M, Karg C, Tindale I, Greene E, Luthuli N, Baepanye K, Hural J, Gomez Lorenzo MM, Burns D, Miner MD, Ledgerwood J, Mascola JR, Donnell D, Cohen MS, Corey L; HVTN 703/HPTN 081 Team. A Phase 2b Study to Evaluate the Safety and Efficacy of VRC01 Broadly Neutralizing Monoclonal Antibody in Reducing Acquisition of HIV-1 Infection in Women in Sub-Saharan Africa: Baseline Findings. J Acquir Immune Defic Syndr. 2021 May 1;87(1):680-687. doi: 10.1097/QAI.0000000000002649.

  PMID: 33587510 RESULT

• Huang Y, Naidoo L, Zhang L, Carpp LN, Rudnicki E, Randhawa A, Gonzales P, McDermott A, Ledgerwood J, Lorenzo MMG, Burns D, DeCamp A, Juraska M, Mascola J, Edupuganti S, Mgodi N, Cohen M, Corey L, Andrew P, Karuna S, Gilbert PB, Mngadi K, Lazarus E. Pharmacokinetics and predicted neutralisation coverage of VRC01 in HIV-uninfected participants of the Antibody Mediated Prevention (AMP) trials. EBioMedicine. 2021 Feb;64:103203. doi: 10.1016/j.ebiom.2020.103203. Epub 2021 Jan 23.

  PMID: 33493795 RESULT

• Huang Y, Zhang L, Eaton A, Mkhize NN, Carpp LN, Rudnicki E, DeCamp A, Juraska M, Randhawa A, McDermott A, Ledgerwood J, Andrew P, Karuna S, Edupuganti S, Mgodi N, Cohen M, Corey L, Mascola J, Gilbert PB, Morris L, Montefiori DC. Prediction of serum HIV-1 neutralization titers of VRC01 in HIV-uninfected Antibody Mediated Prevention (AMP) trial participants. Hum Vaccin Immunother. 2022 Dec 31;18(1):1908030. doi: 10.1080/21645515.2021.1908030. Epub 2021 Jul 2.

  PMID: 34213402 RESULT

• Corey L, Gilbert PB, Juraska M, Montefiori DC, Morris L, Karuna ST, Edupuganti S, Mgodi NM, deCamp AC, Rudnicki E, Huang Y, Gonzales P, Cabello R, Orrell C, Lama JR, Laher F, Lazarus EM, Sanchez J, Frank I, Hinojosa J, Sobieszczyk ME, Marshall KE, Mukwekwerere PG, Makhema J, Baden LR, Mullins JI, Williamson C, Hural J, McElrath MJ, Bentley C, Takuva S, Gomez Lorenzo MM, Burns DN, Espy N, Randhawa AK, Kochar N, Piwowar-Manning E, Donnell DJ, Sista N, Andrew P, Kublin JG, Gray G, Ledgerwood JE, Mascola JR, Cohen MS; HVTN 704/HPTN 085 and HVTN 703/HPTN 081 Study Teams. Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition. N Engl J Med. 2021 Mar 18;384(11):1003-1014. doi: 10.1056/NEJMoa2031738.

  PMID: 33730454 RESULT

• Reeves DB, Mayer BT, deCamp AC, Huang Y, Zhang B, Carpp LN, Magaret CA, Juraska M, Gilbert PB, Montefiori DC, Bar KJ, Cardozo-Ojeda EF, Schiffer JT, Rossenkhan R, Edlefsen P, Morris L, Mkhize NN, Williamson C, Mullins JI, Seaton KE, Tomaras GD, Andrew P, Mgodi N, Ledgerwood JE, Cohen MS, Corey L, Naidoo L, Orrell C, Goepfert PA, Casapia M, Sobieszczyk ME, Karuna ST, Edupuganti S. High monoclonal neutralization titers reduced breakthrough HIV-1 viral loads in the Antibody Mediated Prevention trials. Nat Commun. 2023 Dec 14;14(1):8299. doi: 10.1038/s41467-023-43384-y.

  PMID: 38097552 DERIVED

• Huang Y, Zhang L, Karuna S, Andrew P, Juraska M, Weiner JA, Angier H, Morgan E, Azzam Y, Swann E, Edupuganti S, Mgodi NM, Ackerman ME, Donnell D, Gama L, Anderson PL, Koup RA, Hural J, Cohen MS, Corey L, McElrath MJ, Gilbert PB, Lemos MP. Adults on pre-exposure prophylaxis (tenofovir-emtricitabine) have faster clearance of anti-HIV monoclonal antibody VRC01. Nat Commun. 2023 Nov 28;14(1):7813. doi: 10.1038/s41467-023-43399-5.

  PMID: 38016958 DERIVED

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: Jessica Andriesen, PhD, Associate Director of HVTN SDMC Operations
• Organization: Fred Hutchinson Cancer Research Center

jandries@fredhutch.org

206-667-5812

Study Officials

• Lawrence Corey

  HVTN; FHCRC

  STUDY CHAIR

• Myron Cohen

  HPTN; University of North Carolina

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2016
• First Posted: March 23, 2016
• Study Start: April 6, 2016
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: February 23, 2022
• Results First Posted: February 8, 2022

Record last verified: 2022-02

Locations

PE (5); BR (1); CH (1); US (19)