A Phase 1 Clinical Trial to Evaluate the Safety and Pharmacokinetics of VRC-HIVMAB075-00-AB (VRC07-523LS) in the Sera and Mucosae of Healthy, HIV-1-Uninfected Adult Participants
Overview
- Phase
- Phase 1
- Intervention
- VRC07-523LS
- Conditions
- HIV Infections
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 28
- Locations
- 2
- Primary Endpoint
- Number of Participants Reporting Local Reactogenicity Signs and Symptoms
- Status
- Completed
- Last Updated
- 11 months ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety and pharmacokinetics of a human monoclonal antibody (VRC07-523LS) in the sera and mucosae of healthy, HIV-uninfected adults.
Detailed Description
This study will evaluate the safety and pharmacokinetics of a human monoclonal antibody (VRC07-523LS) in the sera and mucosae of healthy, HIV-uninfected adults. Participants will be randomly assigned to one of two groups. Participants in Group 1 will receive 10 mg/kg of VRC07-523LS at Weeks 0, 16, and 32. Participants in Group 2 will receive 30 mg/kg of VRC07-523LS at Weeks 0, 16, and 32. Study visits will occur at Weeks 0, 2, 16, 18, 32, 34, and 48. Visits may include physical examinations; blood and urine collection; rectal, cervicovaginal, and seminal secretion collection; cervical, rectal, and vaginal biopsy collection; HIV testing; risk reduction counseling; and questionnaires. Study staff will contact participants at Week 50 for follow-up safety monitoring.
Investigators
Eligibility Criteria
Inclusion Criteria
- •General and Demographic Criteria
- •Age of 18 to 50 years
- •Access to a participating HIV Vaccine Trials Network (HVTN) 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.
Exclusion Criteria
- •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 128 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-HVTN HIV antibody testing during the planned duration of the 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 128 PSRT will determine eligibility on a case-by-case basis.
- •Previous receipt of humanized or human monoclonal antibodies (mAbs), whether licensed or investigational; the HVTN 128 PSRT will determine eligibility on a case-by-case basis.
- •Previous receipt of monoclonal antibodies against HIV
- •Immune System
Arms & Interventions
Group 1: VRC07-523LS
Participants will receive 10 mg/kg of VRC07-523LS at Weeks 0, 16, and 32.
Intervention: VRC07-523LS
Group 2: VRC07-523LS
Participants will receive 30 mg/kg of VRC07-523LS at Weeks 0, 16, and 32.
Intervention: VRC07-523LS
Outcomes
Primary Outcomes
Number of Participants Reporting Local Reactogenicity Signs and Symptoms
Time Frame: Measured through 3 days after each infusion at weeks 0, 16 and 32
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017. The maximum grade observed for each symptom over the time frame is presented.
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms
Time Frame: Measured through 3 days after each infusion at weeks 0, 16 and 32
Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017. The maximum grade observed for each symptom over the time frame is presented
Chemistry and Hematology Laboratory Measures - Alanine Aminotransferase (ALT) in U/L
Time Frame: Measured during screening, visit 4(day 14), 6 (day 126) and 8 (day 238)
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.
Chemistry and Hematology Laboratory Measures- Hemoglobin and Creatinine (g/dl)
Time Frame: Measured during screening, Day 14, 126, 238
For each local laboratory measure-Hemoglobin and Creatinine (g/dl), summary statistics were presented by treatment group and time point for the overall population.
Chemistry and Hematology Laboratory Measures- Lymphocyte Count, Neutrophil Count, Platelets, White Blood Cells (WBC)
Time Frame: Measured during screening, Day 14, 126, 238
For each local laboratory measure lymphocyte count, neutrophil count, platelets, white blood cells (WBC) in 1000/ cubic mm summary statistics were presented by treatment group and time point
Chemistry and Hematology Laboratory Measures
Time Frame: Measured during screening, Day 14, 126, 238
Counts of lab grade \>1 for ALT, creatine, hemoglobin, lymphocyte count, neutrophil, platelets, white blood cells
Unnormalized Levels of VRC07-523LS in Genital and Rectal Secretions, as Well as Cervical, Vaginal, and Rectal Tissues at the Collection Timepoints
Time Frame: Measured at Visits 2, 4, 5, 6, 7, 8, 9 (Weeks -2, 2, 16, 18, 32, 34, 48) in secretion samples (semen, cervicovaginal, and rectal) and at Visits 2, 4, 8, 9 (Weeks -2, 2, 34, 48) in biopsy samples (rectal, cervical, and vaginal).
Pharmacokinetic - Single Molecule Counting (PK-SMC) assay were used to measure passively infused VRC07-523LS broadly neutralizing monoclonal antibody in participant mucosa (secretions and biopsies) using 5C9 anti-idiotype antibody (anti-ID). Outcome measure is the concentration of VRC07-523LS.
Number of Participants Reporting Adverse Events (AEs)
Time Frame: Enrollment through week 48
Participants Max severity reported per participant over visit.
Number of Participants With Early Discontinuation of Vaccinations and Reason for Discontinuation
Time Frame: Enrollment through last scheduled dose at week 32
The number (percentage) of participants with early discontinuation of vaccinations and reason for discontinuation was summarized by arm
IgG-normalized Levels of VRC07-523LS in Genital and Rectal Secretions, as Well as Cervical, Vaginal, and Rectal Tissues at the Collection Timepoints
Time Frame: Measured at Visits 2, 4, 5, 6, 7, 8, 9 (Weeks -2, 2, 16, 18, 32, 34, 48) in secretion samples (semen, cervicovaginal, and rectal) and at Visits 2, 4, 8, 9 (Weeks -2, 2, 34, 48) in biopsy samples (rectal, cervical, and vaginal).
Pharmacokinetic - Single Molecule Counting (PK-SMC) assay were used to measure passively infused VRC07-523LS broadly neutralizing monoclonal antibody in participant mucosa (secretions and biopsies) using 5C9 anti-idiotype antibody (anti-ID). Outcome measure is the IgG-normalized VRC07-523LS levels performed by dividing VRC07-523LS levels (pg/mL) by the total IgG (ng/mL).
Protein-normalized Levels of VRC07-523LS in Genital and Rectal Secretions, as Well as Cervical, Vaginal, and Rectal Tissues at the Collection Timepoints
Time Frame: Measured at Visits 2, 4, 5, 6, 7, 8, 9 (Weeks -2, 2, 16, 18, 32, 34, 48) in secretion samples (semen, cervicovaginal, and rectal) and at Visits 2, 4, 8, 9 (Weeks -2, 2, 34, 48) in biopsy samples (rectal, cervical, and vaginal).
Pharmacokinetic - Single Molecule Counting (PK-SMC) assay were used to measure passively infused VRC07-523LS broadly neutralizing monoclonal antibody in participant mucosa (secretions and biopsies) using 5C9 anti-idiotype antibody (anti-ID). Outcome measure is the protein-normalized VRC07-523LS levels performed by dividing VRC07-523LS levels (pg/mL) by the total protein (ng/mL).
Unnormalized Levels of VRC07-523LS in Serum Out to Week 48, 16 Weeks After the Last Product Administration
Time Frame: Measured at Visits 2, 4, 5, 6, 7, 8, 9 (Weeks -2, 2, 16, 18, 32, 34, 48).
Pharmacokinetic - Binding Antibody Multiplex Assay (PK-BAMA) was used to measure levels of passively infused VRC07-523LS broadly neutralizing monoclonal antibody in participant sera using 5C9 anti-IDiotype antibody (anti-ID). Outcome measure is the concentration of VRC07-523LS.
IgG-normalized Levels of VRC07-523LS in Serum Out to Week 48, 16 Weeks After the Last Product Administration
Time Frame: Measured at Visits 2, 4, 5, 6, 7, 8, 9 (Weeks -2, 2, 16, 18, 32, 34, 48).
Pharmacokinetic - Binding Antibody Multiplex Assay (PK-BAMA) was used to measure levels of passively infused VRC07-523LS broadly neutralizing monoclonal antibody in participant sera using 5C9 anti-IDiotype antibody (anti-ID). Outcome measure is the IgG-normalized VRC07-523LS levels performed by dividing VRC07-523LS levels (pg/mL) by the average reference values for total IgG concentrations in serum in the USA (11,650,000 ng/mL).
Protein-normalized Levels of VRC07-523LS in Serum Out to Week 48, 16 Weeks After the Last Product Administration
Time Frame: Measured at Visits 2, 4, 5, 6, 7, 8, 9 (Weeks -2, 2, 16, 18, 32, 34, 48).
Pharmacokinetic - Binding Antibody Multiplex Assay (PK-BAMA) was used to measure levels of passively infused VRC07-523LS broadly neutralizing monoclonal antibody in participant sera using 5C9 anti-idiotype antibody (anti-ID). Outcome measure is the protein-normalized VRC07-523LS levels performed by dividing VRC07-523LS levels (pg/mL) by the total protein (ng/mL).
Secondary Outcomes
- Serum Concentration of ADA in Each Group Measured at Multiple Timepoints From Baseline Through the Final Study Visit(Measured at Visits 2, 3, 5, 7, and 9 (Weeks -2, 0, 16, 32, 48). However, Tier 3 ADA titers are only assessed and reported at Visits 2 and 3 (Weeks -2 and 0) for the subset of participants who tested positive for ADA Tiers 1 and 2.)