Clinical trial NCT06627257: Trial LEP-F1 + GLA-SE in Healthy Adult in Areas Endemic for Leprosy
Official title: A Phase 1b, Double-Blind, Randomized, Placebo-Controlled, Antigen Dose-Escalation Clinical Trial to Evaluate the Safety, Tolerability, and Immunogenicity of LEP-F1 + GLA-SE in Healthy Adult Participants in Areas Endemic for Leprosy
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Leprosy
Lead sponsor: The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)
Sponsor class: OTHER
Collaborators: name: Oswaldo Cruz Institute
First posted: 2024-10-04
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: This is a phase 1b, double-blind, randomized, placebo-controlled clinical trial to evaluate the safety, tolerability, and immunogenicity of LEP-F1 + GLA-SE compared to placebo administered as three intramuscular (IM) injections in adult participants aged 18 to 55.

Detailed description: The LepVax Clinical Development Plan includes two indications for use. The first would be the prophylactic indication, where individuals at greater risk, such as contacts of patients affected by leprosy and who may be subclinically infected with M. leprae, would be vaccinated. This concept is not unique and many countries, such as Brazil, re-immunize leprosy patients and their close contacts with BCG (5, 12, 13). The proposed clinical trial, however, is to establish an initial safety profile in a leprosy endemic region where healthy adults will be included. The second use indication is for therapeutic indication of the vaccine that would be an adjuvant to the current treatment for leprosy. After vaccine safety is established, phase 2 protocols in leprosy patients will be proposed to assess vaccine dose and safety in this population, and then move on to phase 3, where vaccine efficacy will be evaluated.

This phase 1b, double-blind, randomized, placebo-controlled clinical trial will evaluate the safety, tolerability, and immunogenicity of LEP-F1 + GLA-SE in healthy adults. Two dose levels of LEP-F1 will be tested (2 and 10 µg of LEP-F1) and a fixed dose of 5 µg of GLA-SE in adults. These doses were selected because they demonstrated an acceptable safety and immunogenicity profile in the LEPVPX-118 study, the first clinical trial in humans. This study will establish a safety and immunogenicity profile in an endemic population that will allow the vaccine to advance in clinical development.

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, including safety laboratory analyses 7 days following each study injection. Blood samples will be obtained for immunological assays at Days 0, 35, 63, and 168.

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 subjects of childbearing potential must 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 breastfeeding and must use at least one method of contraception from the time of study enrollment (Day 0) through 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 WBC 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:

* History of infection with Mycobacterium leprae.
* History of exposure to experimental products containing GLA-SE.
* History of active tuberculosis or documented recurrence.
* History of previous infection with other non-tuberculous mycobacteria.
* Participation in another trial protocol and/or receipt of any trial products in the last 3 months prior to screening.
* Treatment with immunosuppressive drugs (eg, oral or injectable steroids such as prednisone; high-dose inhaled steroids) or cytotoxic therapies (eg, chemotherapy or radiotherapy) within six months prior to screening.
* Have received blood transfusion within the last 3 months prior to screening.
* Donated blood products (platelets, whole blood, plasma, etc.) within the last month prior to screening.
* Received any vaccine 1 month prior to screening or planned immunizations during the follow-up from D0 to D63 and D154 to D168.
* History of autoimmune disease or other immunosuppressive causes.
* History of any other uncompensated acute or chronic disease (including cardiovascular, pulmonary, neurological, hepatic, rheumatic, hematological, metabolic or renal disease, uncontrolled hypertension) or use of medications that, in the opinion of the Principal Investigator, may interfere with safety or immunogenicity of the vaccine.
* Rash, tattoos, or any other dermatological condition that may adversely affect the injection site of the vaccine or interfere with its evaluation.
* Body mass index (BMI) ≥ 32.
* Systemic arterial hypertension (systolic \> 150 or diastolic \> 95).
* History of psychiatric illness with current medication use.
* Alcohol or drug abuse in the last 6 months prior to screening.
* Chronic smoker (1 pack or more per day).
* History of previous anaphylaxis or severe allergic reaction to unknown vaccines or allergens.
* Individuals who do not wish to cooperate with all procedures recommended in the study protocol.

Primary outcomes:
measure: Phase 1b_The number of participants who receive the injection and experience local and systemic reactions within 7 days of each study injection.
timeFrame: 7 days following each injection
measure: Phase 1b_Number of participants experiencing unsolicited AEs
timeFrame: Day 0 to Day 84 following each injection
measure: Phase 1b_The number of physician-attended adverse events
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: Phase 1b_IgG antibody responses to LEP-F1 by ELISA on Days 0, 35, 63,and 168.
timeFrame: Days 0, 35, 63 and 168
measure: 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
timeFrame: Days 0, 35, 63 and 168
Other outcomes:
measure: The T cell responses measured by multiparametric flow cytometry in PBMCs
timeFrame: Days 0,35,63 and 168
measure: Phase 1b_The assays of candidate biomarkers measured on Day 0 and 63 including gene expression signatures and serum protein multiplex assay.
timeFrame: Day 0 and 63]
Locations:
city: Rio de Janeiro
country: Brazil
facility: Oswaldo Cruz Institue
state: RJ
Study officials:
References:
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