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

NCT06627257 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ASCLIN 001/2023
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Leprosy

Outcome Measures

Primary Outcomes (3)

• Phase 1b_The number of participants who receive the injection and experience local and systemic reactions within 7 days of each study 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

  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

  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 Outcomes (2)

• Phase 1b_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

  Days 0, 35, 63 and 168

Other Outcomes (2)

• The T cell responses measured by multiparametric flow cytometry in PBMCs

  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.

  Day 0 and 63]

Study Arms (2)

LepVax

EXPERIMENTAL

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; Drug: LepVax (10 μg LEP-F1 + 5 μg GLA-SE): High dose

Placebo groups

PLACEBO COMPARATOR

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

Interventions

LepVax (2 μg LEP-F1 + 5 μg GLA-S): Low dose DRUG

2 μg LEP-F1 + 5 μg GLA-SE will be administered by IM injection on Days 0,28, and 56 in healthy participants.

Also known as: LepVax

LepVax

LepVax (10 μg LEP-F1 + 5 μg GLA-SE): High dose DRUG

10 μg LEP-F1 + 5 μg GLA-SE will be administered by IM injection on Days 0,28, and 56 in healthy participants.

Also known as: LepVax

LepVax

Placebo Comparator: Placebo OTHER

Sterile normal saline for injection will be administered by IM injection on Days 0, 28, and 56 in healthy participants and paucibacillary leprosy patients.

Also known as: Sterile normal saline for injection.

Placebo groups

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz): lead
• Oswaldo Cruz Institute: collaborator

Study Sites (1)

Oswaldo Cruz Institue

Rio de Janeiro, Rio de Janeiro, 21040-360, Brazil

Location

Related Publications (13)

• Duthie MS, Frevol A, Day T, Coler RN, Vergara J, Rolf T, Sagawa ZK, Marie Beckmann A, Casper C, Reed SG. A phase 1 antigen dose escalation trial to evaluate safety, tolerability and immunogenicity of the leprosy vaccine candidate LepVax (LEP-F1 + GLA-SE) in healthy adults. Vaccine. 2020 Feb 11;38(7):1700-1707. doi: 10.1016/j.vaccine.2019.12.050. Epub 2019 Dec 30.

  PMID: 31899025 BACKGROUND

• Cunha SS, Alexander N, Barreto ML, Pereira ES, Dourado I, Maroja Mde F, Ichihara Y, Brito S, Pereira S, Rodrigues LC. BCG revaccination does not protect against leprosy in the Brazilian Amazon: a cluster randomised trial. PLoS Negl Trop Dis. 2008 Feb 13;2(2):e167. doi: 10.1371/journal.pntd.0000167.

  PMID: 18270542 BACKGROUND

• Duppre NC, Camacho LA, da Cunha SS, Struchiner CJ, Sales AM, Nery JA, Sarno EN. Effectiveness of BCG vaccination among leprosy contacts: a cohort study. Trans R Soc Trop Med Hyg. 2008 Jul;102(7):631-8. doi: 10.1016/j.trstmh.2008.04.015. Epub 2008 Jun 2.

  PMID: 18514242 BACKGROUND

• Bertholet S, Goto Y, Carter L, Bhatia A, Howard RF, Carter D, Coler RN, Vedvick TS, Reed SG. Optimized subunit vaccine protects against experimental leishmaniasis. Vaccine. 2009 Nov 23;27(50):7036-45. doi: 10.1016/j.vaccine.2009.09.066. Epub 2009 Sep 26.

  PMID: 19786136 BACKGROUND

• Baldwin SL, Bertholet S, Kahn M, Zharkikh I, Ireton GC, Vedvick TS, Reed SG, Coler RN. Intradermal immunization improves protective efficacy of a novel TB vaccine candidate. Vaccine. 2009 May 18;27(23):3063-71. doi: 10.1016/j.vaccine.2009.03.018. Epub 2009 Mar 26.

  PMID: 19428920 BACKGROUND

• Olugbile S, Kulangara C, Bang G, Bertholet S, Suzarte E, Villard V, Frank G, Audran R, Razaname A, Nebie I, Awobusuyi O, Spertini F, Kajava AV, Felger I, Druilhe P, Corradin G. Vaccine potentials of an intrinsically unstructured fragment derived from the blood stage-associated Plasmodium falciparum protein PFF0165c. Infect Immun. 2009 Dec;77(12):5701-9. doi: 10.1128/IAI.00652-09. Epub 2009 Sep 28.

  PMID: 19786562 BACKGROUND

• Baldwin SL, Shaverdian N, Goto Y, Duthie MS, Raman VS, Evers T, Mompoint F, Vedvick TS, Bertholet S, Coler RN, Reed SG. Enhanced humoral and Type 1 cellular immune responses with Fluzone adjuvanted with a synthetic TLR4 agonist formulated in an emulsion. Vaccine. 2009 Oct 9;27(43):5956-63. doi: 10.1016/j.vaccine.2009.07.081. Epub 2009 Aug 11.

  PMID: 19679214 BACKGROUND

• Global leprosy update, 2014: need for early case detection. Wkly Epidemiol Rec. 2015 Sep 4;90(36):461-74. No abstract available. English, French.

  PMID: 26343055 BACKGROUND

• Scollard DM. The biology of nerve injury in leprosy. Lepr Rev. 2008 Sep;79(3):242-53.

  PMID: 19009974 BACKGROUND

• Coler RN, Bertholet S, Moutaftsi M, Guderian JA, Windish HP, Baldwin SL, Laughlin EM, Duthie MS, Fox CB, Carter D, Friede M, Vedvick TS, Reed SG. Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant. PLoS One. 2011 Jan 26;6(1):e16333. doi: 10.1371/journal.pone.0016333.

  PMID: 21298114 BACKGROUND

• Merle CS, Cunha SS, Rodrigues LC. BCG vaccination and leprosy protection: review of current evidence and status of BCG in leprosy control. Expert Rev Vaccines. 2010 Feb;9(2):209-22. doi: 10.1586/erv.09.161.

  PMID: 20109030 BACKGROUND

• Setia MS, Steinmaus C, Ho CS, Rutherford GW. The role of BCG in prevention of leprosy: a meta-analysis. Lancet Infect Dis. 2006 Mar;6(3):162-70. doi: 10.1016/S1473-3099(06)70412-1.

  PMID: 16500597 BACKGROUND

• Wilder-Smith EP, Van Brakel WH. Nerve damage in leprosy and its management. Nat Clin Pract Neurol. 2008 Dec;4(12):656-63. doi: 10.1038/ncpneuro0941. Epub 2008 Nov 11.

  PMID: 19002133 BACKGROUND

Related Links

• Scollard DM. The biology of nerve injury in leprosy. Lepr Rev 2008; 79:242-53.
• Wilder-Smith EP, Van Brakel WH. Nerve damage in leprosy and its management. Nature clinical practice. Neurology 2008; 4:656-63.
• OMS. 2015. Global leprosy update, 2014: need for early case detection. Wkly Epidemiol Rec 2014; 90:461-74.
• Setia MS, Steinmaus C, Ho CS, Rutherford GW. The role of BCG in prevention of leprosy: a meta-analysis. Lancet Infect Dis 2006; 6:162-70.
• Merle CS, Cunha SS, Rodrigues LC. BCG vaccination and leprosy protection: review of current evidence and status of BCG in leprosy control. Expert review of vaccines 2010;9: 209-22
• Coler RN, Bertholet S, Moutaftsi M, et al. Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant. PLoS One 2011; 6: e16333
• Olugbile S, Kulangara C, Bang G, et al. Vaccine potentials of an intrinsically unstructured fragment derived from the blood stage-associated Plasmodium falciparum protein PFF0165c. Infect Immun 2009; 77:5701-5709
• Baldwin SL, Bertholet S, Kahn M, et al. Intradermal immunization improves protective efficacy of a novel TB vaccine candidate. Vaccine 2009; 27:3063-3071
• Bertholet S, Goto Y, Carter L, et al. Optimized subunit vaccine protects against experimental leishmaniasis. Vaccine 2009; 27:7036-7045
• Duppre NC, Camacho LA, da Cunha SS, et al. Effectiveness of BCG vaccination among leprosy contacts: a cohort study. Trans R Soc Trop Med Hyg 2008; 102:631- 8
• Cunha SS, Alexander N, Barreto ML, et al. BCG Revaccination Does Not Protect Against Leprosy in the Brazilian Amazon: A Cluster Randomised Trial. PLoS Negl Trop Dis 2008; 2: e167
• Duthie MS, Frevol A, Day T, Coler RN, Vergara J, Rolf T, et al. A phase 1 antigen dose escalation trial to evaluate safety, tolerability and immunogenicity of the leprosy vaccine candidate LepVax (LEP-F1 + GLA-SE) in healthy adults. Vaccine. 11 de fev

MeSH Terms

Conditions

Leprosy

Interventions

Injections

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Central Study Contacts

Cassio P Ferreira, PhD, Principal investigator

CONTACT

+ 55 (21) 2562-1527; cassio.ferreira@ioc.fiocruz.br

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind study. Participants, investigators, study personnel performing any study-related assessments following study injection, and laboratory personnel performing immunology assays will be blinded to treatment assignment.
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2023
• First Posted: October 4, 2024
• Study Start: January 2, 2025
• Primary Completion: March 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: October 4, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)