Phase 1b/2a Trial to Evaluate LEP-F1 + GLA-SE in Healthy Adults and Leprosy Patients

• ClinicalTrials.gov Identifier: NCT03947437
• Recruitment Status: Not yet recruiting
• First Posted: May 13, 2019
• Last Update Posted: September 16, 2021
• Sponsor: The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)
• Collaborator: Oswaldo Cruz Institute
• Information provided by (Responsible Party): The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Leprosy	Biological: LEP-F1 + GLA-SE; Biological: Placebo	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: Participants, investigators, outcomes assessors, and laboratory personnel performing immunology assays will be blinded to treatment assignment. However, the study product administrators will be unblinded due to a difference in product appearance. These personnel will not be involved in study-related assessments or have participant contact for data collection following study injection.
• Primary Purpose: Treatment
• Official Title: 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
• Estimated Study Start Date: January 2022
• Estimated Primary Completion Date: April 2022
• Estimated Study Completion Date: September 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	Biological: LEP-F1 + GLA-SE; Leprosy antigen formulated with an adjuvant.; Other Name: LepVax
Experimental: 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.	Biological: LEP-F1 + GLA-SE; Leprosy antigen formulated with an adjuvant.; Other Name: LepVax
Experimental: TBD dose in patients; TBD μg LEP-F1 + 5 μg GLA-SE will be administered by IM injection on Days 0, 28, and 56 in paucibacillary leprosy patients. Dose will be determined by safety and immunogenicity data from healthy participants.	Biological: LEP-F1 + GLA-SE; Leprosy antigen formulated with an adjuvant.; Other Name: LepVax
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.	Biological: Placebo; Sterile normal saline for injection.

Outcome Measures

Primary Outcome Measures :

1. Number of participants experiencing solicited AEs [ Time Frame: 7 days following each injection ]
2. Number of participants experiencing unsolicited AEs [ Time Frame: Days 0 to 84 ]
3. Number of participants experiencing medically-attended adverse events considered related to any of the study injections [ Time Frame: Days 0 to 421 ]

Secondary Outcome Measures :

1. IgG antibody responses to LEP-F1 by ELISA [ Time Frame: Days 0, 35, and 63 ]
2. T cell responses measured by selected cytokine production to LEP-F1 by whole blood assay [ Time Frame: Days 0, 35, and 63 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Males and females ≥ 18 years and ≤ 55 years of age.
2. For Cohort 1, participants must be in good general health as confirmed by a medical history and physical exam. For Cohort 2, patients must have confirmed diagnosis of paucibacillary leprosy.
3. Female participants of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test on the day of each study vaccination, must not be breast-feeding, and are required to use one of the following methods of contraception from enrollment in study until 30 days after last injection (only if in sexual relationships with men): hormonal (e.g. oral, transdermal, intravaginal, implant, or injection); double barrier (i.e., condom, diaphragm, or cervical cap with spermicide); intrauterine device (IUD) or system (IUS); vasectomized partner (6 months minimum); or abstinence; bilateral tubal ligation (if no conception post-procedure); tubal occlusion; or bilateral salpingectomy. These precautions are necessary due to unknown effects that LEP-F1 + GLA-SE might cause in a fetus or newborn infant. Women are considered non-child-bearing potential if they are post-menopausal (menopause defined as at least 12 months spontaneous amenorrhea) or have had documented hysterectomy and/or oophorectomy.
4. Screening laboratory values within the normal ranges or not clinically significant as determined by the Investigator and approved by the Medical Monitor: sodium, potassium, ALT, AST, total bilirubin, alkaline phosphatase, creatinine, fasting glucose, total WBC count, hemoglobin, and platelet count. Abnormal results may be repeated once for confirmation at Investigator discretion.
5. Negative HIV 1/2 antibody, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, and QuantiFERON®-TB Gold (QFT).
6. Normal or not clinically significant urinalysis as determined by the study clinician or designee. Abnormal results may be repeated at Investigator discretion.
7. Subject is capable of completing a study memory aid.
8. Subject gave informed consent, is able and willing to make all evaluation visits, is reachable by telephone or personal contact by the study site personnel, and is willing to remain in the study area for the duration of the trial.

Exclusion Criteria:

1. For Cohort 1, history of infection with M. leprae.
2. Previous exposure to M. leprae vaccines or experimental products containing GLA-SE.
3. History of active or documented latent TB.
4. History of previous infection with other non-tuberculous mycobacteria.
5. Participation in another experimental protocol and/or receipt of any investigational products within the past 3 months prior to Enrollment.
6. Received any vaccine within 30 days prior to Enrollment or plan to have any immunizations between Days 0-63 due to the washout period prior to immunology blood draws.
7. Received a blood transfusion within 3 months prior to Enrollment.
8. Donated blood products (platelets, whole blood, plasma, etc.) within 30 days prior to Enrollment.
9. Treatment with immunosuppressive drugs (e.g., oral or injected steroids, such as prednisone; high dose inhaled steroids) or cytotoxic therapies (e.g., chemotherapy drugs or radiation) in the past 6 months prior to Enrollment.
10. History of autoimmune disease or other causes of immunosuppressive states.
11. History of any other acute or chronic illness (including cardiovascular, pulmonary, neurological, hepatic, rheumatic, hematological, metabolic or renal disorders, uncontrolled hypertension), or use of medication that, in the opinion of the Principal Investigator, may interfere with the evaluation of the safety or immunogenicity of the vaccine.
12. Rash, tattoos, or any other dermatological condition that could adversely affect the vaccine injection site or interfere with its evaluation.
13. BMI ≥ 32.
14. Hypertension (systolic > 150 or diastolic > 95).
15. History of significant psychiatric illness with current use of medication.
16. Known or suspected alcohol or drug abuse within the past 6 months prior to Screening.
17. Smokes 1 pack or more of cigarettes per day.
18. History of previous anaphylaxis or severe allergic reaction to vaccines or unknown allergens.
19. Participants who are unlikely to cooperate with the requirements of the study protocol.

Contacts and Locations

Contacts

Contact: Cassio Porto Ferreira, PhD; +552125621588 ext 1588; cassio.ferreira@fiocruz.br

Contact: Milton Moraes, PhD; +552125621573 ext 1573; milton.moraes@fiocruz.br

Locations

Brazil

Oswaldo Cruz Institute (Fiocruz)

Rio de Janeiro, Rj, Cep, Brazil, 21040-900

Principal Investigator: Cassio P Ferreira, PHD

Principal Investigator: Milton O Moraes, PHD

Sponsors and Collaborators

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

Oswaldo Cruz Institute

Investigators

• Principal Investigator: Milton Moraes, PhD; Oswaldo Cruz Institute

More Information

• Responsible Party: The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)
• ClinicalTrials.gov Identifier: NCT03947437
• Other Study ID Numbers: IDRI-LEPVPX-119
• First Posted: May 13, 2019
• Last Update Posted: September 16, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Leprosy; Mycobacterium Infections, Nontuberculous; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections