A Phase 1 Clinical Trial 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 Adult Participants
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV Infections
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 27
- Locations
- 4
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
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 130/HPTN 089 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 130/HPTN 089 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 130/HPTN 089 PSRT will determine eligibility on a case-by-case basis.
- •Previous receipt of humanized or human mAbs, whether licensed or investigational; the HVTN 130/HPTN 089 PSRT will determine eligibility on a case-by-case basis.
- •Previous receipt of monoclonal antibodies VRC01, VRC01LS, VRC07-523LS, PGT121, PGDM1400, or 10-1074
- •Immune System
Outcomes
Primary Outcomes
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
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
Chemistry and Hematology Laboratory Measures - Lymphocyte Count, Neutrophil Count in 1000 Cells/Cubic mm
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
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.
Chemistry and Hematology Laboratory Measures - Alanine Aminotransferase (ALT) in U/L
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
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.
Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Pain and/or Tenderness
Time Frame: Measured through 3 days after each vaccine dose at T1-T3: Day 0 and T4: Days 0, 112
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.
Chemistry and Hematology Laboratory Measures - Hemoglobin in g/dL
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
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms
Time Frame: Measured through 3 days after each vaccine dose at T1-T3: Day 0 and T4: Days 0, 112
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.
Chemistry and Hematology Laboratory Measures - Creatinine in mg/dL
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
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.
Chemistry and Hematology Laboratory Measures - Platelets, WBC in 1000 Cells/Cubic mm
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
For each local laboratory measure, summary statistics were presented by treatment group and timepoint for the overall population.
Number of Participants Reporting Local Reactogenicity Signs and Symptoms: Erythema and/or Induration
Time Frame: Measured through 3 days after each vaccine dose at T1-T3: Day 0 and T4: Days 0, 112
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.
Number of Participants With Early Discontinuation of Vaccinations and Reason for Discontinuation
Time Frame: Measured through Month 4
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.
Secondary Outcomes
- Magnitudes of TZM-bl Cells Responses Against mAb-specific Env-pseudotyped Viruses Among Participants Who Received All Scheduled Product Administrations(Measured during Screening, Days 0, 3, 28, 56, 112, 140*, 168*, 224* Days with * are only available for T4)
- Serum Concentration Levels of PGT121, PGDM1400, and VRC07-523LS Among Participants Who Received All Scheduled Product Administrations(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)
- Serum Concentrations of PGT121, PGDM1400, 10-1074, and VRC07-523LS for All Participants(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)
- Magnitude of Neutralizing Activity Against a Panel of Env Pseudotyped Reference Viruses in TZM-bl Cells for All Participants(Measured during Screening, Days 0*, 3, 28, 56*, 112, 140*, 224* Days with * are only available for T4)
- Magnitudes of TZM-bl Cells Responses Against a Panel of Env Pseudotyped Viruses for All Participants(Measured during Screening, Days 0, 3, 28, 56, 112, 140*, 168*, 224* Days with * are only available for T4)