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

Studies

Study First Submitted Date 2019-05-09
Study First Posted Date 2019-05-13
Last Update Posted Date 2023-06-13
Start Month Year February 2024
Primary Completion Month Year March 2024
Verification Month Year June 2023
Verification Date 2023-06-30
Last Update Posted Date 2023-06-13

Detailed Descriptions

Sequence: 20547395
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.

Facilities

Sequence: 198391972
Name Veronica Schmitz Pereira
City Rio de Janeiro
Zip FIOCRUZ – 33.781.055/0001
Country Brazil

Facility Contacts

Sequence: 27916486 Sequence: 27916487
Facility Id 198391972 Facility Id 198391972
Contact Type primary Contact Type backup
Name Veronica S Pereira, PHD Name Cassio P Ferreira, PHD
Email veronicaschmitz@ioc.fiocruz.br Email cassio.ferreira@ioc.fiocruz.br
Phone +55 (21) 2562-1579
Phone Extension 1579

Facility Investigators

Sequence: 18214096 Sequence: 18214097
Facility Id 198391972 Facility Id 198391972
Role Principal Investigator Role Principal Investigator
Name Cassio P Ferreira, PHD Name Veronica S Pereira, PHD

Conditions

Sequence: 51723718
Name Leprosy
Downcase Name leprosy

Id Information

Sequence: 39802936
Id Source org_study_id
Id Value ASCLIN 002/2020

Countries

Sequence: 42201896
Name Brazil
Removed False

Design Groups

Sequence: 55143300 Sequence: 55143301 Sequence: 55143302 Sequence: 55143303
Group Type Experimental Group Type Experimental Group Type Experimental Group Type Placebo Comparator
Title Low dose Title High dose Title TBD dose in patients Title Placebo
Description 2 μg LEP-F1 + 5 μg GLA-SE will be administered by IM injection on Days 0, 28, and 56 in healthy participants. Description 10 μg LEP-F1 + 5 μg GLA-SE will be administered by IM injection on Days 0, 28, and 56 in healthy participants. Description 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. Description 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

Sequence: 52045208 Sequence: 52045209
Intervention Type Biological Intervention Type Biological
Name LEP-F1 + GLA-SE Name Placebo
Description Leprosy antigen formulated with an adjuvant. Description Sterile normal saline for injection.

Design Outcomes

Sequence: 175921406 Sequence: 175921407 Sequence: 175921408 Sequence: 175921409 Sequence: 175921410 Sequence: 175921411 Sequence: 175921412 Sequence: 175921413 Sequence: 175921414 Sequence: 175921415 Sequence: 175921416 Sequence: 175921417 Sequence: 175921418 Sequence: 175921419 Sequence: 175921420 Sequence: 175921421 Sequence: 175921422 Sequence: 175921423 Sequence: 175921424 Sequence: 175921425 Sequence: 175921426
Outcome Type primary Outcome Type primary Outcome Type primary Outcome Type primary Outcome Type primary Outcome Type primary Outcome Type primary Outcome Type primary Outcome Type primary Outcome Type primary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type secondary Outcome Type other Outcome Type other Outcome Type other Outcome Type other
Measure Phase 1b_The number of participants who receive the injection and experience local and systemic reactions within 7 days of each study injection. Measure Phase 1b_Number of participants experiencing unsolicited AEs Measure Phase 1b_The number of adverse events attended by physicians considered related to any of the study injections reported at any time during the study period. Measure Phase 1b_The LEP-F1 specific T cell IFN–γ production responses in assay with PBMCs evaluated by ELISA on Days 0, 35 and 63. Measure Phase 2a_The number of participants who receive the injection and experience local and systemic reactions within 7 days of each study injection. Measure Phase 2a_The number of participants spontaneously reporting adverse events from Day 0 to Day 84. Measure Phase 2a_The number of physician-assisted adverse events considered related to any of the study injections reported at any time during the study period Measure Phase 2a_The frequency and intensity of solicited adverse events within 7 days of each study injection. Measure Phase 2a_The frequency and intensity of unsolicited adverse events during study participation (D0 to D421). Measure Phase 2a_The frequency and causality of serious adverse events occurring during study participation (D0 to D421). Measure Phase 1b_IgG antibody responses to LEP-F1 by ELISA on 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 Measure Phase 2a_IgG antibody responses to LEP-F1 by ELISA on Days 0, 35, 63, and 168. Measure Phase 2a_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. Measure Phase 2a_The neurological nerve function as measured by clinical and neurophysiological tests Measure Phase 2a_The number of participants who received LepVax and had episodes of RR after the start of the study. Measure Phase 2a_The number of M. leprae genome copies (bacillus quantification). Measure Phase 1b_The T cell responses measured by intracellular cytokine (ICS) staining in PBMCs on 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. Measure Phase 2a_The T cell responses measured by intracellular cytokine staining of PBMCs on Days 0, 35, 63 and 168 Measure Phase 2a_The Assays of candidate biomarkers measured on Day 0 and 63 including gene expression signatures and serum protein multiplex assay
Time Frame 7 days following each injection Time Frame Days 0 to 84 Time Frame Days 0 to 421 Time Frame Days 0, 35 and 63. Time Frame 7 days following each injection Time Frame Day 0 to Day 84. Time Frame Day 0 to Day 421 Time Frame 7 days following each injection Time Frame Day 0 to Day 421 Time Frame Day 0 to Day 421 Time Frame Days 0, 35, and 63 Time Frame Days 0, 35, 63 and 168 Time Frame Days 0, 35, 63, and 168. Time Frame on Days 0, 35, 63, and 168. Time Frame Day 0 to Day 421 Time Frame Day 0 to Day 421 Time Frame Day 0 to Day 421 Time Frame Days 0, 35, 63, and 168. Time Frame Day 0 and 163 Time Frame Days 0, 35, 63 and 168 Time Frame Day 0 and 63
Description The number of participants who receive the injection and experience local and systemic reactions within 7 days of each study injection. Description The number of participants spontaneously reporting adverse events from Day 0 to Day 84. Description The number of adverse events attended by physicians considered related to any of the study injections reported at any time during the study period. Description The LEP-F1 specific T cell IFN-γ production responses in assay with PBMCs evaluated by ELISA on Days 0, 35 and 63. Description The number of participants who receive the injection and experience local and systemic reactions within 7 days of each study injection. Description The number of participants spontaneously reporting adverse events from Day 0 to Day 84. Description The number of physician-assisted adverse events considered related to any of the study injections reported at any time during the study period Description The frequency and intensity of solicited adverse events within 7 days of each study injection. Description The frequency and intensity of unsolicited adverse events during study participation (D0 to D421). Description The frequency and causality of serious adverse events occurring during study participation (D0 to D421). Description IgG antibody responses to LEP-F1 by ELISA on Days 0, 35, 63, and 168 Description 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. Description IgG antibody responses to LEP-F1 by ELISA on Days 0, 35, 63, and 168. Description 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. Description The neurological nerve function as measured by clinical and neurophysiological tests Description The number of participants who received LepVax and had episodes of RR after the start of the study. Description The number of M. leprae genome copies (bacillus quantification). Description The T cell responses measured by intracellular cytokine (ICS) staining in PBMCs on Days 0, 35, 63, and 168. Description The assays of candidate biomarkers measured on Day 0 and 63 including gene expression signatures and serum protein multiplex assay. Description The T cell responses measured by intracellular cytokine staining of PBMCs on Days 0, 35, 63 and 168 Description The Assays of candidate biomarkers measured on Day 0 and 63 including gene expression signatures and serum protein multiplex assay

Browse Conditions

Sequence: 191687056 Sequence: 191687057 Sequence: 191687058 Sequence: 191687059 Sequence: 191687060 Sequence: 191687061 Sequence: 191687062 Sequence: 191687063
Mesh Term Leprosy Mesh Term Mycobacterium Infections, Nontuberculous Mesh Term Mycobacterium Infections Mesh Term Actinomycetales Infections Mesh Term Gram-Positive Bacterial Infections Mesh Term Bacterial Infections Mesh Term Bacterial Infections and Mycoses Mesh Term Infections
Downcase Mesh Term leprosy Downcase Mesh Term mycobacterium infections, nontuberculous Downcase Mesh Term mycobacterium infections Downcase Mesh Term actinomycetales infections Downcase Mesh Term gram-positive bacterial infections Downcase Mesh Term bacterial infections Downcase Mesh Term bacterial infections and mycoses Downcase Mesh Term infections
Mesh Type mesh-list Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor Mesh Type mesh-ancestor

Sponsors

Sequence: 47903966 Sequence: 47903967
Agency Class OTHER Agency Class UNKNOWN
Lead Or Collaborator lead Lead Or Collaborator collaborator
Name The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz) Name Oswaldo Cruz Institute

Overall Officials

Sequence: 29025054
Role Principal Investigator
Name Veronica Schmitz Pereira, PHD
Affiliation Instituto Oswaldo Cruz

Central Contacts

Sequence: 11918380 Sequence: 11918381
Contact Type primary Contact Type backup
Name Cassio Porto Ferreira, PhD Name Veronica Schmitz Pereira, PhD
Phone +552125621588 Phone +55 (21) 2562-1579
Email cassio.ferreira@fiocruz.br Email veronicaschmitz@ioc.fiocruz.br
Phone Extension 1588 Phone Extension 1579
Role Contact Role Contact

Design Group Interventions

Sequence: 67602870 Sequence: 67602871 Sequence: 67602872 Sequence: 67602873
Design Group Id 55143301 Design Group Id 55143300 Design Group Id 55143302 Design Group Id 55143303
Intervention Id 52045208 Intervention Id 52045208 Intervention Id 52045208 Intervention Id 52045209

Eligibilities

Sequence: 30504622
Gender All
Minimum Age 18 Years
Maximum Age 55 Years
Healthy Volunteers Accepts Healthy Volunteers
Criteria Phase 1b

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 participants of childbearing age should 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 breast-feeding and are required to use at least one contraceptive method from the time of study inclusion (Day 0) until 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 leukocyte 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 (Phase 1b)

Individuals who meet ANY of the following criteria will be considered ineligible:

History of infection with Mycobacterium leprae.
History of exposure to experimental products containing GLA-SE.
History of active or documented latent tuberculosis.
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 injected steroids, such as prednisone; high doses of inhaled steroids) or cytotoxic therapies (eg chemotherapy or radiation) within 6 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 acute or chronic decompensated disease (including cardiovascular, pulmonary, neurological, hepatic, rheumatic, haematological, metabolic or renal disease, uncontrolled hypertension) or use of medication 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.

Inclusion Criteria (Phase 2a)

Participants must meet ALL of the following criteria listed below to be included in the study:

Men and women between 18 and 55 years old.
Diagnosis of PB leprosy (BI=0) before MDT treatment
Female participants of childbearing age should 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 breast-feeding and are required to use at least one contraceptive method from the time of study inclusion (Day 0) until 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 leukocyte 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 (Phase 2a)

Individuals who meet ANY of the following criteria will be considered ineligible:

Previous treatment for leprosy.
History of exposure to experimental products containing GLA-SE.
History of active or documented latent tuberculosis.
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 injected steroids, such as prednisone; high doses of inhaled steroids) or cytotoxic therapies (eg chemotherapy or radiation) within 6 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 acute or chronic decompensated disease (including cardiovascular, pulmonary, neurological, hepatic, rheumatic, haematological, metabolic or renal disease, uncontrolled hypertension) or use of medication 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.

Vital signs are performed after participants have sat for five minutes without hot or cold drinks or smoking for the past five minutes. Vital signs can be performed up to three times to allow resolution of transient conditions.

Adult True
Child False
Older Adult False

Calculated Values

Sequence: 254049834
Number Of Facilities 1
Registered In Calendar Year 2019
Were Results Reported False
Has Us Facility False
Has Single Facility True
Minimum Age Num 18
Maximum Age Num 55
Minimum Age Unit Years
Maximum Age Unit Years
Number Of Primary Outcomes To Measure 10
Number Of Secondary Outcomes To Measure 7
Number Of Other Outcomes To Measure 4

Designs

Sequence: 30253710
Allocation Randomized
Intervention Model Parallel Assignment
Observational Model
Primary Purpose Treatment
Time Perspective
Masking Double
Masking Description 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.
Intervention Model Description 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
Subject Masked True
Investigator Masked True

Intervention Other Names

Sequence: 26454060
Intervention Id 52045208
Name LepVax

Responsible Parties

Sequence: 28634194
Responsible Party Type Sponsor