VRC 615: A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of a Human Monoclonal Antibody, VRC-HIVMAB-0115-AB (VRC01.23LS), Administered Intravenously or Subcutaneously to Healthy Adults
Overview
- Phase
- Phase 1
- Intervention
- VRC-HIVMAB0115-00-AB
- Conditions
- HIV
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Product Administration
- Status
- Completed
- Last Updated
- 8 months ago
Overview
Brief Summary
Background:
HIV causes AIDS, a serious disease that can lead to fatal infections. HIV infection can be controlled but not cured, nor is there a vaccine to prevent it. Antibodies may offer a promising new way to prevent HIV infection. Antibodies are proteins that are naturally made by the body to fight germs. One antibody (VRC01.23LS) has been tested in the lab and was found to block HIV-like viruses. Researchers want to find out if it is safe to inject VRC01.23LS into people.
Objective:
To test the safety of VRC01.23LS in healthy adults.
Eligibility:
Healthy people aged 18 to 60 years.
Design:
Participants were divided into 6 groups:
Some got 1 dose of VRC01.23LS. They visited the clinic up to 14 times in 24 weeks.
Some got 3 doses, each 12 weeks apart. They had 25 clinic visits over 48 weeks.
For some participants, the drug was given through a tube attached to a needle inserted into a vein in the arm. This took about 30 to 90 minutes. Others received the drug as an injection under the skin in a fatty area of the belly, arm, or thigh; each dose may have needed up to 3 individual injections.
Participants stayed in the clinic up to 8 hours on the days they received VRC01.23LS.
Participants received a thermometer and measuring tool. They checked their temperature daily for 7 days after they received the study drug. They measured any redness, swelling, or bruising at the injection site.
Detailed Description
Study Design: This first-in-human, open-label study evaluated VRC01.23LS (VRCHIVMAB0115- 00-AB) in a dose-escalation design to examine safety, tolerability, dose, and pharmacokinetics (PK) in healthy adults. The primary hypothesis was that subcutaneous (SC) and intravenous (IV) administrations of VRC01.23LS will be safe and well-tolerated in healthy adults. A secondary hypothesis was that VRC01.23LS will be detectable in human sera with a definable half-life. Study Products: The VRC01.23LS broadly neutralizing monoclonal antibody (bnAb) targets the CD4 binding site in the HIV-1 envelope, is human in origin, and contains two amino acid modifications within the C-terminus of the heavy chain constant region designed to improve the antibody half-life in vivo. VRC01.23LS was developed by the VRC/NIAID/NIH and manufactured under cGMP regulations at the VRC Pilot Plant operated under contract by the Vaccine Clinical Materials Program (VCMP), Leidos Biomedical Research, Inc., Frederick. MD. Subjects: Healthy adults, 18-60 years of age Study Plan: This open-label study included 6 groups to evaluate VRC01.23LS administered as a single dose or as repeated doses, given 12 weeks apart as shown in the table below. Enrollment began with the 5 mg/kg dose groups, and enrollment in subsequent dose groups proceeded after dose-escalation safety reviews. Assessment of safety included solicited reactogenicity, clinical observation, and monitoring of hematological and metabolic parameters at clinical visits throughout the study.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Group 1
5 mg/kg IV single administration
Intervention: VRC-HIVMAB0115-00-AB
Group 2
5 mg/kg SC single administration
Intervention: VRC-HIVMAB0115-00-AB
Group 3
20 mg/kg IV single administration
Intervention: VRC-HIVMAB0115-00-AB
Group 4
40 mg/kg IV single administration
Intervention: VRC-HIVMAB0115-00-AB
Group 5
5 mg/kg SC repeat dosing
Intervention: VRC-HIVMAB0115-00-AB
Group 6
20 mg/kg IV repeat dosing
Intervention: VRC-HIVMAB0115-00-AB
Outcomes
Primary Outcomes
Number of Participants Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Product Administration
Time Frame: 7 days after product administration
Participants recorded the occurrence of solicited local symptoms on a diary card for 7 days after study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Local Symptom" is the number of participants reporting any local symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (Corrected Version 2.1 - July 2017)
Number of Participants Reporting Systemic Reactogenicity Signs and Symptoms Within 7 Days of Product Administration
Time Frame: 7 days after product administration
Participants recorded the occurrence of solicited systemic symptoms on a diary card for 7 days after study product administration and reviewed the diary card with clinic staff at a follow up visit. Participants were counted once for each symptom at the worst severity if they indicated experiencing the symptom more than one time at any severity during the reporting period. The number reported for "Any Systemic Symptom" is the number of participants reporting any systemic symptom at the worst severity. Reactogenicity grading (Mild, Moderate, Severe) was done using the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (Corrected Version 2.1 - July 2017
Number of Participants With Serious Adverse Events Following Product Administration
Time Frame: Day 0 after product administration through Day 168, up to Week 24 for participants in Groups 1-4. Day 0 after product administration through Day 336, up to Week 48, for participants in Group 5 and 6.
SAEs were recorded from receipt of product administration through the last study visit at Week 24 for participants in Groups 1, 2, 3, 4. SAEs were recorded from receipt of product administration through the last study visit at Week 48 for participants in Groups 5 or 6. The relationship between a SAE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.
Number of Participants With One or More Unsolicited Non-Serious Adverse Events (AEs) Following Product Administration
Time Frame: Day 0 through 28 days post product administration, up to Week 4
Unsolicited AEs and attribution assessments were recorded in the study database from receipt of study product administration through the visit scheduled for 4 weeks after study product administration. At other time periods greater than 4 weeks after the study product administration, only serious AEs (SAEs reported as a separate outcome and in the AE module) and new chronic medical conditions were recorded through the last study visit. The relationship between an AE and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.
Number of Participants With New Chronic Medical Conditions Following Product Administration
Time Frame: Day 0 after product administration through Day 140, up to Week 24 for Groups 1-4. Day 0 after product administration through Day 336, up to Week 48 for Groups 5-6
New chronic medical conditions that required ongoing medical management were recorded from receipt of study product administration through the last expected study visit at Week 24 for Groups 1-4 and through Week 48 for Groups 5-6. The relationship between a new chronic medical condition and the study product was assessed by the investigator based on clinical judgment and the definitions outlined in the protocol. A participant with multiple experiences of the same event is counted once using the event of worst severity.
Number of Participants With Abnormal Laboratory Measures of Safety Following Product Administration
Time Frame: Day 0 after product administration through Day 140, up to Week 24 for Groups 1-4. Day 0 after product administration through Day 336, up to Week 48, for Groups 5-6
Abnormal lab results recorded as unsolicited adverse events (AEs) are summarized. Safety lab parameters included pregnancy test, hematology and chemistry labs, and HIV Serology diagnostic test. Institutional lab normal ranges as well as the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 - July 2017 were used.
Secondary Outcomes
- Pharmacokinetic (PK) Parameters of VRC01.23LS: Maximum Observed Serum Concentration (Cmax)(Baseline through 24 weeks after VRC01.23LS product administration)
- Pharmacokinetic (PK) Parameters of VRC01.23LS: Time to Reach Maximum Observed Serum Concentration (Tmax)(Baseline through 24 weeks after VRC01.23LS product administration)
- Pharmacokinetic (PK) Parameters of VRC01.23LS: Beta Half-life (T1/2b)(Baseline through 24 weeks after VRC01.23LS product administration)
- Pharmacokinetic (PK) Parameters of VRC01.23LS: Clearance Rate(Baseline through 24 weeks after VRC01.23LS product administration)
- Pharmacokinetic (PK) Parameters of VRC01.23LS: Volume of Distribution(Baseline through 24 weeks after VRC01.23LS product administration)