The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of the monoclonal antibody PGT121.414.LS administered alone and in combination with VRC07-523LS via intravenous or subcutaneous infusions in healthy, HIV-uninfected adult participants.
This study will evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of the monoclonal antibody PGT121.414.LS administered alone and in combination with VRC07-523LS via intravenous (IV) or subcutaneous (SC) infusions in healthy, HIV-uninfected adult participants. The study will be conducted in two parts (Part A and B). Part A will include four groups (Groups 1, 2, 3, and 4) and Part B will include two groups (Groups 5 and 6). In Part A of the study, PGT121.414.LS will be administered via IV infusion at 3, 10, or 30 mg/kg (Groups 1-3) or via SC infusion at 5 mg/kg (Group 4). Participants in Part B will receive consecutive administration of PGT121.414.LS followed by VRC07-523LS, at 20 mg/kg IV each per dose (Group 5) or 5 mg/kg SC each per dose (Group 6). Participants will be followed for 32 weeks after the last study product administration via IV infusion and 24 weeks after the last study product administration via SC infusion. Participants in Groups 1, 2, and 3 will attend 8 months of study visits. Participants in Group 4 will attend 6 months of study visits. Part B participants will attend 16 months of study visits. Study visits may include physical examinations, blood and urine collection, and questionnaires.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
33
Administered via IV infusion or SC infusion, depending on the arm
Administered via IV infusion or SC infusion, depending on the arm
UCLA CARE Center CRS
Los Angeles, California, United States
George Washington Univ. CRS
Washington D.C., District of Columbia, United States
The Hope Clinic of the Emory Vaccine Center CRS
Decatur, Georgia, United States
Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
Boston, Massachusetts, United States
Columbia P&S CRS
New York, New York, 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 T1-T4: Day 0; T5-T6: Days 0, 112, 224
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 T1-T4: Day 0; T5-T6: Days 0, 112, 224
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 T1-T4: Day 0; T5-T6: Days 0, 112, 224
Chemistry and Hematology Laboratory Measures - Alkaline Phosphatase, AST, ALT in U/L
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, 112, 168
Chemistry and Hematology Laboratory Measures - Creatinine in mg/dL
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, 112, 168
Chemistry and Hematology Laboratory Measures - Hemoglobin in g/dL
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, 112, 168
Chemistry and Hematology Laboratory Measures - Lymphocyte Count, Neutrophil Count in 1000 Cells/Cubic mm
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, 112, 168
Chemistry and Hematology Laboratory Measures - Platelets, WBC in 1000 Cells/Cubic mm
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, 112, 168
Number of Participants Reporting Unsolicited Adverse Events (AEs)
The number (percentage) of Participants Reporting Unsolicited Adverse Events (AEs) was summarized by arm
Time frame: Measured through Month 24
Number of Participants With Early Discontinuation of Vaccinations and Reason for Discontinuation
The number (percentage) of participants with early discontinuation of vaccinations and reason for discontinuation was summarized by arm
Time frame: Measured through Month 8
Number of Participants With Early Study Termination and Reason for Early Study Termination
The number (percentage) of participants with early study termination and reason for early study termination was summarized by arm
Time frame: Measured through Month 16
PGT121.414.LS and VRC07523LS Serum Concentrations
Serum concentrations of PGT121.414.LS and VRC07-523LS at prespecified timepoints among participants who received all scheduled product administrations
Time frame: Days 0, 0.0417, 1, 2, 3, 6, 14, 28, 56, 84, 112, 112.0417, 140, 168, 196, 224, 224.0417, 252, 280, 336, 392, 448
Magnitude of Serum Neutralizing Activity Measured With mAb-specific Env-pseudotyped Viruses in TZM-bl Cells
Level of ID50 and ID80 titer data from the TZMbl neutralizing antibody assays against 1 bnAb-specific virus (CH505TF.N334S.N160A.N280D.1, sensitive to PGT121, resistant to VRC07) for all Part A participants (IV or SC administration of PGT121.414.LS alone), and 1 bnAb-specific virus (CNE55.N160K, sensitive to VRC07, resistant to PGT121) for all Part B participants (IV or SC administration of PGT121.414.LS in combination with VRC07523LS) at all expected timepoints.
Time frame: Day 3, Months 1, 2, 4, 6, 8, 10, 12
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, 112, 196, 224, 336, 392, 448
Magnitude and Breadth of Neutralizing Antibody Responses Against Autologous Viral Isolates as Assessed by Area Under the Magnitude-breadth Curves at Months 1, 4, and 9
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: 0330.v4.c3, 3426.v5.c17, 377.v4.c09, AC10.0.29, Ce1176\_A3, DU156.12, DU172.17, PVO.4, RHPA4259.7, SC422661.8, T2638, andTRO.11.
Time frame: Months 1, 4, and 9
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