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

NCT ID: NCT06627257

Last Updated: 2024-10-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

54 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-01-02

Study Completion Date

2026-08-31

Brief Summary

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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

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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.

Conditions

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Leprosy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
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.

Study Groups

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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.

Group Type EXPERIMENTAL

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

Intervention Type DRUG

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

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

Intervention Type DRUG

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

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.

Group Type PLACEBO_COMPARATOR

Placebo Comparator: Placebo

Intervention Type 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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

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.

Intervention Type OTHER

Other Intervention Names

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LepVax LepVax Sterile normal saline for injection.

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Oswaldo Cruz Institute

UNKNOWN

Sponsor Role collaborator

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

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Oswaldo Cruz Institue

Rio de Janeiro, Rio de Janeiro, Brazil

Site Status

Countries

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Brazil

Central Contacts

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Cassio P Ferreira, PhD, Principal investigator

Role: CONTACT

+ 55 (21) 2562-1527

Facility Contacts

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Cassio P Ferreira, PhD

Role: primary

Veronica S Perreira, PhD

Role: backup

References

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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.

Reference Type BACKGROUND
PMID: 31899025 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18270542 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18514242 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19786136 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19428920 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19786562 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19679214 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 26343055 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 19009974 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21298114 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20109030 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16500597 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19002133 (View on PubMed)

Related Links

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https://pubmed.ncbi.nlm.nih.gov/19009974/

Scollard DM. The biology of nerve injury in leprosy. Lepr Rev 2008; 79:242-53.

https://www.who.int/publications/i/item/who-wer9036

OMS. 2015. Global leprosy update, 2014: need for early case detection. Wkly Epidemiol Rec 2014; 90:461-74.

https://www.scielo.br/j/rimtsp/a/9RLy8qtHTSfdYWSfKXKr8rc/

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.

https://www.ncbi.nlm.nih.gov/books/NBK78956/

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

https://pubmed.ncbi.nlm.nih.gov/21298114/

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

https://pubmed.ncbi.nlm.nih.gov/19786562/

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

https://pubmed.ncbi.nlm.nih.gov/19428920/

Baldwin SL, Bertholet S, Kahn M, et al. Intradermal immunization improves protective efficacy of a novel TB vaccine candidate. Vaccine 2009; 27:3063-3071

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2783536/

Bertholet S, Goto Y, Carter L, et al. Optimized subunit vaccine protects against experimental leishmaniasis. Vaccine 2009; 27:7036-7045

https://pubmed.ncbi.nlm.nih.gov/18514242/

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

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2238709/

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

https://pubmed.ncbi.nlm.nih.gov/31899025/

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

Other Identifiers

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ASCLIN 001/2023

Identifier Type: -

Identifier Source: org_study_id

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