A Phase 1b / 2a, Double-Blind, Randomized, Placebo-Controlled, Antigen Dose-Escalation Clinical Trial to Evaluate the Safety, Tolerability, and Immunogenicity of LEP-F1 + GLA-SE in Adult Participants in Areas Endemic for Leprosy
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Leprosy
- Sponsor
- The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)
- Enrollment
- 142
- Locations
- 1
- Primary Endpoint
- Phase 1b_The number of participants who receive the injection and experience local and systemic reactions within 7 days of each study injection.
- Status
- Not yet recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a phase 1b/2a, double-blind, randomized, placebo-controlled clinical trial to evaluate the safety, tolerability, and immunogenicity of the LEP-F1 + GLA-SE investigational vaccine compared to placebo.
Detailed Description
The proposed clinical trial will establish an initial safety profile for the vaccine in a region endemic for leprosy. The trial will enroll both healthy participants and paucibacillary leprosy patients receiving standard-of-care therapy. Safety at the lower vaccine dose will be demonstrated in healthy participants prior to antigen dose-escalation. Further, safety in all healthy participants will be demonstrated prior to enrolling leprosy patients. Participants will be randomized within each Group to receive three doses of vaccine or placebo administered IM on Days 0, 28, and 56. Participants will be monitored for one year following the last study injection.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Men and women between 18 and 55 years old.
- •They should be in good general health, confirmed by a medical history and physical examination, with negative clinical evaluation for leprosy.
- •Female participants of childbearing age should have a negative serum pregnancy test at screening and a negative urine pregnancy test on study vaccination days (D0, D28 and D56). They must not be breast-feeding and are required to use at least one contraceptive method from the time of study inclusion (Day 0) until 30 days after the last injection if they have sex with men.
- •Screening laboratory tests with normal, within laboratory reference limits for:: sodium, potassium, AST, ALT, total bilirubin, alkaline phosphatase, creatinine, glucose, total leukocyte count, hemoglobin and platelet count. Abnormal results may be repeated at the discretion of the Principal Investigator and/or sub-investigators, who may share doubts with the sponsor's Scientific Leader and if necessary with the DSMB.
- •Negative serological tests for: HIV 1/2 antibody, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibody.
- •Normal or not clinically significant urinalysis as determined by the study doctor or designee. Abnormal results may be repeated at the discretion of the Principal Investigator.
- •Must be able to complete the study adverse events diary.
- •Must consent to participate in the study, be able and willing to make all evaluation visits, be accessible by telephone or home visits, and live in the region until study follow-up completion.
- •Having completed the primary vaccination course for Covid 19, at least 14 days before inclusion in the study. If 14 days have not been completed, the participant may be rescheduled for a new eligibility assessment
- •Exclusion Criteria (Phase 1b)
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Phase 1b_The number of participants who receive the injection and experience local and systemic reactions within 7 days of each study injection.
Time Frame: 7 days following each injection
The number of participants who receive the injection and experience local and systemic reactions within 7 days of each study injection.
Phase 2a_The number of participants spontaneously reporting adverse events from Day 0 to Day 84.
Time Frame: Day 0 to Day 84.
The number of participants spontaneously reporting adverse events from Day 0 to Day 84.
Phase 2a_The frequency and intensity of unsolicited adverse events during study participation (D0 to D421).
Time Frame: Day 0 to Day 421
The frequency and intensity of unsolicited adverse events during study participation (D0 to D421).
Phase 2a_The frequency and causality of serious adverse events occurring during study participation (D0 to D421).
Time Frame: Day 0 to Day 421
The frequency and causality of serious adverse events occurring during study participation (D0 to D421).
Phase 1b_Number of participants experiencing unsolicited AEs
Time Frame: Days 0 to 84
The number of participants spontaneously reporting adverse events from Day 0 to Day 84.
Phase 1b_The number of adverse events attended by physicians considered related to any of the study injections reported at any time during the study period.
Time Frame: Days 0 to 421
The number of adverse events attended by physicians considered related to any of the study injections reported at any time during the study period.
Phase 2a_The number of participants who receive the injection and experience local and systemic reactions within 7 days of each study injection.
Time Frame: 7 days following each injection
The number of participants who receive the injection and experience local and systemic reactions within 7 days of each study injection.
Phase 2a_The number of physician-assisted adverse events considered related to any of the study injections reported at any time during the study period
Time Frame: Day 0 to Day 421
The number of physician-assisted adverse events considered related to any of the study injections reported at any time during the study period
Phase 2a_The frequency and intensity of solicited adverse events within 7 days of each study injection.
Time Frame: 7 days following each injection
The frequency and intensity of solicited adverse events within 7 days of each study injection.
Phase 1b_The LEP-F1 specific T cell IFN--γ production responses in assay with PBMCs evaluated by ELISA on Days 0, 35 and 63.
Time Frame: Days 0, 35 and 63.
The LEP-F1 specific T cell IFN-γ production responses in assay with PBMCs evaluated by ELISA on Days 0, 35 and 63.
Secondary Outcomes
- Phase 1b_IgG antibody responses to LEP-F1 by ELISA on Days 0, 35, 63, and 168.(Days 0, 35, and 63)
- Phase 1b_ The T cell responses measured by LEP-F1-specific cytokine production in PBMC assay by ELISA or multiplex assay on Days 0, 35, 63, and 168.whole blood assay(Days 0, 35, 63 and 168)
- Phase 2a_IgG antibody responses to LEP-F1 by ELISA on Days 0, 35, 63, and 168.(Days 0, 35, 63, and 168.)
- Phase 2a_The number of participants who received LepVax and had episodes of RR after the start of the study.(Day 0 to Day 421)
- Phase 2a_The number of M. leprae genome copies (bacillus quantification).(Day 0 to Day 421)
- Phase 2a_T cell responses measured by LEP-F1-specific cytokine production in PBMC assay by ELISA or multiplex assay on Days 0, 35, 63, and 168.(on Days 0, 35, 63, and 168.)
- Phase 2a_The neurological nerve function as measured by clinical and neurophysiological tests(Day 0 to Day 421)