Trial LEP-F1 + GLA-SE in Healthy Adult in Areas Endemic for Leprosy

October 2, 2024 updated by: The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

54

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Brazil
    • RJ
      • Rio de Janeiro, RJ, Brazil, 21040-360
        • Oswaldo Cruz Institue
        • Contact:
          • Cassio P Ferreira, PhD
        • Contact:
          • Veronica S Perreira, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: LepVax
Participants will be randomized within each Group to receive three doses of vaccine 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.
Drug: LepVax (2 μg LEP-F1 + 5 μg GLA-S): Low dose
2 μg LEP-F1 + 5 μg GLA-SE will be administered by IM injection on Days 0,28, and 56 in healthy participants.
Other Names:
  • LepVax
Drug: LepVax (10 μg LEP-F1 + 5 μg GLA-SE): High dose
10 μg LEP-F1 + 5 μg GLA-SE will be administered by IM injection on Days 0,28, and 56 in healthy participants.
Other Names:
  • LepVax
Placebo Comparator: Placebo groups
Participants will be randomized within each Group to receive three doses of 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.
Other: Placebo Comparator: Placebo
Sterile normal saline for injection will be administered by IM injection on Days 0, 28, and 56 in healthy participants and paucibacillary leprosy patients.
Other Names:
  • Sterile normal saline for injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
7 days following each injection
Phase 1b_Number of participants experiencing unsolicited AEs
Time Frame: Day 0 to Day 84 following each injection
The number of participants spontaneously reporting adverse events from Day 0 to Day 84.
Day 0 to Day 84 following each injection
Phase 1b_The number of physician-attended adverse events
Time Frame: Through study completion, an average of 1 year
The number of physician-attended adverse events considered to be related to any of the study injections reported at any time during the study period.
Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1b_IgG antibody responses to LEP-F1 by ELISA on Days 0, 35, 63,and 168.
Time Frame: Days 0, 35, 63 and 168
IgG antibody responses to LEP-F1 by ELISA on Days 0, 35, 63, and 168
Days 0, 35, 63 and 168
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
Time Frame: Days 0, 35, 63 and 168
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.
Days 0, 35, 63 and 168

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
The T cell responses measured by multiparametric flow cytometry in PBMCs
Time Frame: Days 0,35,63 and 168
The T cell responses measured by multiparametric flow cytometry in PBMCs on Days 0, 35, 63, and 168.
Days 0,35,63 and 168
Phase 1b_The assays of candidate biomarkers measured on Day 0 and 63 including gene expression signatures and serum protein multiplex assay.
Time Frame: Day 0 and 63]
The assays of candidate biomarkers measured on Day 0 and 63 including gene expression signatures and serum protein multiplex assay.
Day 0 and 63]

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)

Collaborators

Oswaldo Cruz Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 2, 2025

Primary Completion (Estimated)

March 1, 2026

Study Completion (Estimated)

August 1, 2026

Study Registration Dates

First Submitted

August 21, 2023

First Submitted That Met QC Criteria

October 2, 2024

First Posted (Actual)

October 4, 2024

Study Record Updates

Last Update Posted (Actual)

October 4, 2024

Last Update Submitted That Met QC Criteria

October 2, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ASCLIN 001/2023

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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