Evaluating the Safety and Serum Concentrations of a Human Monoclonal Antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), Administered in Multiple Doses and Routes to Healthy, HIV-uninfected Adults

NCT03387150 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: HVTN 127/HPTN 08738458
• Study Type: interventional
• Target: 124
• Locations: 2 countries
• Sites: 7

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and serum concentrations of a human monoclonal antibody, VRC-HIVMAB075-00-AB (VRC07-523LS), administered in multiple doses and routes to healthy, HIV-uninfected adults.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (10)

• 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 vaccine dose at Weeks 0, 16, 32, 48, 64

• 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 vaccine dose at Weeks 0, 16, 32, 48, 64

• 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 vaccine dose at Weeks 0, 16, 32, 48, 64

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

  For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.

  Measured during screening, Days 0, 56, 112, 168, 224, 280, 336, 392, 448, 504, 728

• Chemistry and Hematology Laboratory Measures - Creatinine

  For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.

  Measured during screening, Days 0, 56, 112, 168, 224, 280, 336, 392, 448, 504, 728

• Chemistry and Hematology Laboratory Measures - Hemoglobin

  For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.

  Measured during screening, Days 0, 56, 112, 168, 224, 280, 336, 392, 448, 504, 728

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

  For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.

  Measured during screening, Days 0, 56, 112, 168, 224, 280, 336, 392, 448, 504, 728

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

  For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.

  Measured during screening, Days 0, 56, 112, 168, 224, 280, 336, 392, 448, 504, 728

• Number of Lab Grade >= 1 for Alanine Aminotransferase (ALT), Creatinine, Hemoglobin, Lymphocyte Count, Neutrophil Count, Platelets, White Blood Cells (WBC).

  The number (percentage) of participants with lab grade \>= 1 for alanine aminotransferase (ALT), creatinine, hemoglobin, lymphocyte count, neutrophil count, platelets, white blood cells (WBC) was summarized by arm

  Measured during screening, Days 0, 56, 112, 168, 224, 280, 336, 392, 448, 504, 728

• VRC07523LS Serum Concentrations

  VRC07523LS serum concentrations measured in healthy human subjects after up to five administrations of the study product via the IV, SC or IM routes at various doses. Serum concentrations between the first and second study product administrations (Target Visit Day 0-112) were measured using ELISA assay in all enrolled participants. Serum concentrations after the second study product administrations (Target Visit Day 168-784) were measured using BAMA (LUMINEX) assay in a subset of participants enrolled in each treatment group and all particiants in plocebo group. serum concentrations below the lower limit of quantification (LLoQ) were replaced by half the LLoQ. Thus, concentrations below the LLoQ when measured by the ELISA assay were replaced by 0.5 ug/ml and concentrations below the LLoQ when measured by the BAMA assay were replaced by 0.02285 ug/ml.

  Target Visit Days 0, 3, 6, 28, 56, 84, 112, 168, 224, 280, 336, 392, 448, 504, 560, 616, 672, 728, 784 (i.e., visit numbers 2 through 20)

Secondary Outcomes (2)

• Occurrence of Antidrug Antibodies (ADA)

  Day 0, 6, 112, 224, 448

• Magnitude and Breadth of Neutralizing Antibody Responses Against Autologous Viral Isolates as Assessed by Area Under the Magnitude-breadth Curves 8, 72, 88 Weeks After the First Study Product Administration.

  Weeks 8, 72, and 88 following the first study product administration

Study Arms (7)

Group 1: VRC07-523LS

EXPERIMENTAL

Participants in Group 1 will receive 2.5 mg/kg of VRC07-523LS by IV infusion at Weeks 0, 16, 32, 48, and 64.

Biological: VRC07-523LS

Group 2: VRC07-523LS

EXPERIMENTAL

Participants in Group 2 will receive 5 mg/kg of VRC07-523LS by IV infusion at Weeks 0, 16, 32, 48, and 64.

Biological: VRC07-523LS

Group 3: VRC07-523LS

EXPERIMENTAL

Participants in Group 3 will receive 20 mg/kg of VRC07-523LS by IV infusion at Weeks 0, 16, 32, 48, and 64.

Biological: VRC07-523LS

Group 4: VRC07-523LS

EXPERIMENTAL

Participants in Group 4 will receive 2.5 mg/kg of VRC07-523LS by SC injection at Weeks 0, 16, 32, 48, and 64.

Biological: VRC07-523LS

Group 5: VRC07-523LS

EXPERIMENTAL

Participants in Group 5 will receive 5 mg/kg of VRC07-523LS by SC injection at Weeks 0, 16, 32, 48, and 64.

Biological: VRC07-523LS

Group T6 VRC07-523LS

EXPERIMENTAL

Participants in Group T6 will receive 2.5 mg/kg of VRC07-523LS by IM injection at Weeks 0, 16, 32, 48, and 64.

Biological: VRC07-523LS

Group P6: Placebo

PLACEBO COMPARATOR

Participants in Group P6 will receive 2.5 mg/kg of placebo by IM injection at Weeks 0, 16, 32, 48, and 64.

Biological: Placebo

Interventions

VRC07-523LS BIOLOGICAL

Administered by intravenous (IV) infusion, subcutaneous (SC) injection, or intramuscular (IM) injection, depending on which group participants are in

Also known as: VRC-HIVMAB075-00-AB

Group 1: VRC07-523LS; Group 2: VRC07-523LS; Group 3: VRC07-523LS; Group 4: VRC07-523LS; Group 5: VRC07-523LS; Group T6 VRC07-523LS

Placebo BIOLOGICAL

Sodium Chloride for Injection USP, 0.9%; administered by IM injection

Group P6: Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• 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 study product administration with verbal demonstration of understanding of all questionnaire items answered incorrectly
• Agrees not to enroll in another study of an investigational research agent until completion of the last required protocol clinic visit
• 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.
• Assessed by the clinic staff as being at 'low risk' for HIV infection and committed to maintaining behavior consistent with those criteria through the last required protocol clinic visit (see the protocol for more information).
• Hemogram/Complete Blood Count (CBC)
• Hemoglobin greater than or equal to 11.0 g/dL for volunteers who were assigned female sex at birth, greater than or equal to 13.0 g/dL for volunteers who were assigned male sex at birth. For transgender participants who have been on hormone therapy for more than 6 consecutive months, determine hemoglobin eligibility based on the gender with which they identify (ie, a transgender female who has been on hormone therapy for more than 6 consecutive months should be assessed for eligibility using the hemoglobin parameters for volunteers assigned female sex at birth).
• White blood cell (WBC) count equal to 2,500 to 12,000 cells/mm\^3
• WBC differential either within institutional normal range or with site physician approval

You may not qualify if:

• General
• Weight greater than 115 kg
• Blood products received within 120 days before first study product administration, unless eligibility for earlier enrollment is determined by the HVTN 127/HPTN 087 PSRT
• Investigational research agents received within 30 days before first study product administration
• Intent to participate in another study of an investigational research agent or any other study that requires non-Network HIV antibody testing during the planned duration of the HVTN 127/HPTN 087 study
• Pregnant or breastfeeding
• Vaccines and other Injections
• HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 127/HPTN 087 PSRT will determine eligibility on a case-by-case basis.
• Previous receipt of humanized or human mAbs, whether licensed or investigational; the HVTN 127/HPTN 087 PSRT will determine eligibility on a case-by-case basis.
• Previous receipt of monoclonal antibodies VRC01, VRC01LS, or VRC07-523LS
• Immune System
• Serious adverse reactions to VRC07-523LS formulation components, including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain
• Immunoglobulin received within 90 days before first injection or infusion, unless eligibility for earlier enrollment is determined by the HVTN 127/HPTN 087 PSRT
• Autoimmune disease (Not excluded from participation: Volunteer with mild, stable and uncomplicated autoimmune disease that does not require immunosuppressive medication and that, in the judgment of the site investigator, is likely not subject to exacerbation and likely not to complicate Solicited and Unsolicited adverse event (AE) assessments)
• Immunodeficiency

Sponsors & Collaborators

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

Study Sites (7)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

The Ponce de Leon Center CRS

Atlanta, Georgia, 30308-2012, 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

Columbia P&S CRS

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

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27599, United States

Location

Lausanne Vaccine and Immunotherapy Center CRS

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Related Publications (1)

• Walsh SR, Gay CL, Karuna ST, Hyrien O, Skalland T, Mayer KH, Sobieszczyk ME, Baden LR, Goepfert PA, Del Rio C, Pantaleo G, Andrew P, Karg C, He Z, Lu H, Paez CA, Baumblatt JAG, Polakowski LL, Chege W, Anderson MA, Janto S, Han X, Huang Y, Dumond J, Ackerman ME, McDermott AB, Flach B, Piwowar-Manning E, Seaton K, Tomaras GD, Montefiori DC, Gama L, Mascola JR; HVTN 127/HPTN 087 Study Team. Safety and pharmacokinetics of VRC07-523LS administered via different routes and doses (HVTN 127/HPTN 087): A Phase I randomized clinical trial. PLoS Med. 2024 Jun 24;21(6):e1004329. doi: 10.1371/journal.pmed.1004329. eCollection 2024 Jun.

  PMID: 38913710 DERIVED

MeSH Terms

Conditions

HIV Infections

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 Center

jandries@fredhutch.org

206-667-5812

Study Officials

• Stephen Walsh

  Brigham and Women's Hospital

  STUDY CHAIR

• Cynthia Gay

  University of North Carolina, Chapel Hill

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2017
• First Posted: December 29, 2017
• Study Start: February 28, 2018
• Primary Completion: December 7, 2020
• Study Completion: December 7, 2020
• Last Updated: April 5, 2023
• Results First Posted: March 21, 2022

Record last verified: 2023-04

Locations

US (6); CH (1)