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.
This study will 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. Participants will be randomly assigned to one of six groups. Participants in Group 1 will receive 2.5 mg/kg of VRC07-523LS by intravenous (IV) infusion at Weeks 0, 16, 32, 48, and 64. Participants in Group 2 will receive 5 mg/kg of VRC07-523LS by IV infusion at Weeks 0, 16, 32, 48, and 64. Participants in Group 3 will receive 20 mg/kg of VRC07-523LS by IV infusion at Weeks 0, 16, 32, 48, and 64. Participants in Group 4 will receive 2.5 mg/kg of VRC07-523LS by subcutaneous (SC) injection at Weeks 0, 16, 32, 48, and 64. Participants in Group 5 will receive 5 mg/kg of VRC07-523LS by SC injection at Weeks 0, 16, 32, 48, and 64. Participants in Group 6 will receive 2.5 mg/kg of VRC07-523LS or placebo by intramuscular (IM) injection at Weeks 0, 16, 32, 48, and 64. Participants will attend numerous study visits throughout the course of the study, beginning at Week 0 through Week 112. Visits may include physical examinations, blood and urine collection, HIV testing, risk reduction counseling, and questionnaires.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
124
Administered by intravenous (IV) infusion, subcutaneous (SC) injection, or intramuscular (IM) injection, depending on which group participants are in
Sodium Chloride for Injection USP, 0.9%; administered by IM injection
Alabama CRS
Birmingham, Alabama, United States
The Ponce de Leon Center CRS
Atlanta, Georgia, United States
Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
Boston, Massachusetts, United States
Fenway Health (FH) CRS
Boston, Massachusetts, United States
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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
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Columbia P&S CRS
New York, New York, United States
Chapel Hill CRS
Chapel Hill, North Carolina, United States
Lausanne Vaccine and Immunotherapy Center CRS
Lausanne, Canton of Vaud, Switzerland
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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)
Occurrence of Antidrug Antibodies (ADA)
Antidrug antibodies (ADA) are most typically detected and characterized using a tiered testing strategy. In Tier I, a sensitive binding assay is used to determine if samples may have ADA present. In Tier II, the response is confirmed, typically by establishing the specificity of the response by competition with free drug. In Tier III, the response is characterized, typically with a neutralization reduction assay and/or a titering assay.
Time frame: 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.
Magnitude-breadth characterize the magnitude (ID50 or ID80 titers) and breadth (number of virus isolates) of each individual serum sample assayed against a panel of virus isolates. MB curves show, for each possible magnitude threshold, the fraction of assays with magnitudes greater than this threshold. The area under the magnitude-breadth curve (AUC-MB) is calculated as the average of the log10-based ID50 or ID80 titers over the panel of isolates. Isolates includes: H703\_0646\_051sN, H703\_1471\_190s, H703\_1750\_140Es, H704\_0726\_080sN, H704\_1535\_030sN, H704\_2544\_140eN01, PVO.4.
Time frame: Weeks 8, 72, and 88 following the first study product administration