The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of combinations of monoclonal antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS administered via intravenous infusion in healthy, HIV-uninfected adults.
This study will evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of combinations of monoclonal antibodies PGT121, PGDM1400, 10-1074, and VRC07-523LS administered via intravenous infusion in healthy, HIV-uninfected adults. Participants will initially be enrolled into one of three groups. At Day 0, Groups 1, 2, and 3 will receive dual combinations of mAbs administered sequentially via IV. Group 1 will receive a combination of PGT121 and VRC07-523LS, Group 2 will receive PGDM1400 and VRC07-523LS, and Group 3 will receive 10-1074 and VRC07-523LS. Study staff will review study data from Groups 1, 2, and 3 and determine if Group 4 may begin to enroll. Participants in Group 4 will receive PGDM1400, PGT121, and VRC07-523LS administered in sequence via IV on Day 0 and at Month 4. Study duration will be 12 months for participants in Groups 1, 2, and 3, and 16 months for participants in Group 4. Participants will attend several study visits, which may include physical examinations, blood and urine collection, HIV testing and pretest counseling, risk reduction counseling, and questionnaires.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
27
20 mg/kg administered intravenously
20 mg/kg administered intravenously
20 mg/kg administered intravenously
20 mg/kg administered intravenously
Fenway Health (FH) CRS
Boston, Massachusetts, United States
Harlem Prevention Center CRS
New York, New York, United States
Columbia P&S CRS
New York, New York, United States
Vanderbilt Vaccine (VV) CRS
Nashville, Tennessee, 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-T3: Day 0 and T4: Days 0, 112
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-T3: Day 0 and T4: Days 0, 112
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-T3: Day 0 and T4: Days 0, 112
Chemistry and Hematology Laboratory Measures - Alanine Aminotransferase (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, 14, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, and 448*. Days with * are only available for T4
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, 14, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, and 448*. Days with * are only available for T4
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, 14, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, and 448*. Days with * are only available for T4
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, 14, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, and 448*. Days with * are only available for T4
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, 14, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, and 448*. Days with * are only available for T4
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
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, 14, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, 448*, and 504* Days with * are only available for T4
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. The three participants discontinued treatment in T4 were due to the COVID-19 pandemic lockdown.
Time frame: Measured through Month 4
Serum Concentration Levels of PGT121, PGDM1400, and VRC07-523LS Among Participants Who Received All Scheduled Product Administrations
Serum PGDM1400, PGT121, and VRC07-523LS IgG levels were measured on a Bio-Plex instrument (Bio-Rad) using a validated assay designed to simultaneously measure infused PGDM1400, PGT121, and VRC07-523LS by its ability to bind anti-idiotype antibody captured on fluorescent magnetic beads. This assay was derived from a standardized custom HIV-1 Luminex assay. PGDM1400, PGT121 and VRC07-523LS were titrated and combined to create a standard curve that was used to determine concentration of the diluted samples. The negative controls were CH58 (an irrelevant mAb) and blank beads.Serum 10-1074 level was measured by anti-idotypic ELISA. Participant serum sample was incubated in anti-ID coated micro-plate well. A conjugated secondary antibody was used to detect bound 10-1074. Samples were titrated to ensure positive optical density (O.D.) readouts fall within the linear range of the assay for monoclonal antibody concentration calculations.
Time frame: Measured during Screening, Days 0, 3, 6, 14, 28, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, and 448* Days with * are only available for T4
Magnitudes of TZM-bl Cells Responses Against mAb-specific Env-pseudotyped Viruses Among Participants Who Received All Scheduled Product Administrations
Neutralizing antibodies against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells. The assay performed in TZM-bl cells measured neutralization titers against the Env-pseudotyped viruses sensitive to the bnAbs (i.e., bnAb-specific viruses) in each infusion group.
Time frame: Measured during Screening, Days 0, 3, 28, 56, 112, 140*, 168*, 224* Days with * are only available for T4
Serum Concentrations of PGT121, PGDM1400, 10-1074, and VRC07-523LS for All Participants
Serum PGDM1400, PGT121, and VRC07-523LS IgG levels were measured on a Bio-Plex instrument (Bio-Rad) using a validated assay designed to simultaneously measure infused PGDM1400, PGT121, and VRC07-523LS by its ability to bind anti-idiotype antibody captured on fluorescent magnetic beads. This assay was derived from a standardized custom HIV-1 Luminex assay. PGDM1400, PGT121 and VRC07-523LS were titrated and combined to create a standard curve that was used to determine concentration of the diluted samples. The negative controls were CH58 (an irrelevant mAb) and blank beads.Serum 10-1074 level was measured by anti-idotypic ELISA. Participant serum sample was incubated in anti-ID coated micro-plate well. A conjugated secondary antibody was used to detect bound 10-1074. Samples were titrated to ensure positive optical density (O.D.) readouts fall within the linear range of the assay for monoclonal antibody concentration calculations
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Measured during Screening, Days 0, 3, 6, 14, 28, 56, 84*, 112, 140*, 168, 224, 280, 336, 392*, and 448* Days with * are only available for T4
Magnitudes of TZM-bl Cells Responses Against a Panel of Env Pseudotyped Viruses for All Participants
Neutralizing antibodies against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells. The assay performed in TZM-bl cells measured neutralization titers against the Env-pseudotyped viruses sensitive to the bnAbs (i.e., bnAb-specific viruses) in each infusion group.
Time frame: Measured during Screening, Days 0, 3, 28, 56, 112, 140*, 168*, 224* Days with * are only available for T4
Magnitude of Neutralizing Activity Against a Panel of Env Pseudotyped Reference Viruses in TZM-bl Cells for All Participants
Neutralizing antibodies against HIV-1 were measured as a function of reductions in Tat-regulated luciferase (Luc) reporter gene expression in TZM-bl cells. The assay performed in TZM-bl cells measured neutralization titers against the Env-pseudotyped viruses sensitive to the bnAbs (i.e., bnAb-specific viruses) in each infusion group.
Time frame: Measured during Screening, Days 0*, 3, 28, 56*, 112, 140*, 224* Days with * are only available for T4