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Sm-p80 Schistosomiasis Challenge Study

Primary Purpose

Schistosoma Mansoni, Schistosomiasis

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Sm-p80 + GLA-SE Vaccine
Placebo
Schistosoma mansoni infection
Sponsored by
Leiden University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Schistosoma Mansoni

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Subject is aged ≥ 18 and ≤ 45 years and in good health. Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby. Subject is able to communicate well with the investigator, is available to attend all study visits. Subject will not travel to Schistosoma-endemic countries up until treatment at week 24. Subject agrees to refrain from blood and plasma donation to Sanquin or for other purposes throughout the study period. For female subjects: subject agrees to use adequate contraception and not to breastfeed for the duration of study. Subject has signed informed consent. Exclusion Criteria: Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine, malignant, haematological, infectious, immune-deficient, (severe) psychiatric and other disorders, which could compromise the health of the participant during the study or interfere with the interpretation of the study results. These include, but are not limited to, any of the following: body weight <50 kg or Body Mass Index (BMI) <18.0 or >35.0 kg/m2 at screening; positive HIV, HBV or HCV screening tests; the use of immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted) or expected use of such during the study period; history of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years; any history of treatment for severe psychiatric disease by a psychiatrist in the past year; history of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset. The chronic use of any drug known to interact with praziquantel, artesunate or lumefantrine metabolism (e.g. phenytoïn, carbamazepine, phenobarbital, primidon, dexamethason, rifampicine, cimetidine, flecaïnide, metoprolol, imipramine, amitriptyline, clomipramine, class IA and III anti-arrythmics, antipsychotics, antidepressants, macrolides, fluorchinolones, imidazole- and triazole antimycotics, antihistamines). Because lumefantrine may cause extension of QT-time, chronic use of drugs with effect on QT interval will result in exclusion from study participation. Any planned vaccination within 28 days before the start of the trial until the end of the immunisation phase (week 12), with the exception of SARS-CoV-2 vaccines or influenza vaccines. For female subjects: positive serum pregnancy test on the day before first immunisation. Any history of schistosomiasis or treatment for schistosomiasis. Positive serology for schistosomiasis or elevated serum CAA at screening. Known hypersensitivity to or contra-indications (including co-medication) for use of praziquantel, artesunate or lumefantrine. Being an employee or student of the department of Parasitology or Infectious diseases of the LUMC.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Vaccine group

    Placebo control group

    Arm Description

    The vaccine group will be immunised three times with 30 μg Sm-p80 + 5 μg GLA-SE i.m. at weeks 0,4, and 8. Participants will be exposed to 20 male Schistosoma mansoni cercariae at week 12.

    The placebo control group will be immunised three times with saline i.m. at weeks 0,4, and 8. Participants will be exposed to 20 male Schistosoma mansoni cercariae at week 12.

    Outcomes

    Primary Outcome Measures

    Vaccine efficacy
    The protective efficacy of Sm-p80 + GLA-SE to male Sm cercariae measured by the difference in frequency of serum CAA positivity (≥1.0 pg/mL) between the vaccine group and placebo

    Secondary Outcome Measures

    Safety of (repeated) immunisation
    Frequency and severity of adverse events after (repeated) immunisation with Sm-p80 + GLA-SE
    Immunogenicity
    Anti-Sm-p80 IgG antibody titres after (repeated) immunisation with Sm-p80 + GLA-SE measured by ELISA

    Full Information

    First Posted
    August 11, 2023
    Last Updated
    October 16, 2023
    Sponsor
    Leiden University Medical Center
    Collaborators
    Texas Tech University Health Sciences Center, MRC/UVRI and LSHTM Uganda Research Unit
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05999825
    Brief Title
    Sm-p80 Schistosomiasis Challenge Study
    Official Title
    Safety and Preliminary Efficacy of Sm-p80 + GLA-SE (SchistoShield®) Vaccine Against Controlled Human Schistosome Infection in Healthy, Schistosoma-naïve Adults
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 2024 (Anticipated)
    Primary Completion Date
    April 2025 (Anticipated)
    Study Completion Date
    September 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Leiden University Medical Center
    Collaborators
    Texas Tech University Health Sciences Center, MRC/UVRI and LSHTM Uganda Research Unit

    4. Oversight

    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.
    Yes
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The goal of this clinical trial is to learn about the Sm-p80 + GLA-SE (Schistoshield®) vaccine in healthy participants who have not had schistosomiasis before. The main questions it aims to answer are: if the vaccine is safe if after vaccinated people start producing antibodies if the vaccine works against schistosomiasis. Participants will receive three vaccines (or placebo) and are then exposed to 20 male Schistosoma cercariae. Afterwards they are treated with praziquantel to cure the infection. Researchers will compare the group vaccinated with Schistoshield® and placebo (fake vaccination) to see if the vaccine has worked.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Schistosoma Mansoni, Schistosomiasis

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    48 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Vaccine group
    Arm Type
    Experimental
    Arm Description
    The vaccine group will be immunised three times with 30 μg Sm-p80 + 5 μg GLA-SE i.m. at weeks 0,4, and 8. Participants will be exposed to 20 male Schistosoma mansoni cercariae at week 12.
    Arm Title
    Placebo control group
    Arm Type
    Placebo Comparator
    Arm Description
    The placebo control group will be immunised three times with saline i.m. at weeks 0,4, and 8. Participants will be exposed to 20 male Schistosoma mansoni cercariae at week 12.
    Intervention Type
    Biological
    Intervention Name(s)
    Sm-p80 + GLA-SE Vaccine
    Intervention Description
    30 μg Sm-p80 + 5 μg GLA-SE
    Intervention Type
    Other
    Intervention Name(s)
    Placebo
    Intervention Description
    0.9% Sterile Normal Saline
    Intervention Type
    Biological
    Intervention Name(s)
    Schistosoma mansoni infection
    Intervention Description
    20 viable male Schistosoma mansoni cercariae of the Puerto Rican strain
    Primary Outcome Measure Information:
    Title
    Vaccine efficacy
    Description
    The protective efficacy of Sm-p80 + GLA-SE to male Sm cercariae measured by the difference in frequency of serum CAA positivity (≥1.0 pg/mL) between the vaccine group and placebo
    Time Frame
    week 12-24, i.e. after challenge
    Secondary Outcome Measure Information:
    Title
    Safety of (repeated) immunisation
    Description
    Frequency and severity of adverse events after (repeated) immunisation with Sm-p80 + GLA-SE
    Time Frame
    week 0-12
    Title
    Immunogenicity
    Description
    Anti-Sm-p80 IgG antibody titres after (repeated) immunisation with Sm-p80 + GLA-SE measured by ELISA
    Time Frame
    week 0-24
    Other Pre-specified Outcome Measures:
    Title
    Time to CAA positivity
    Description
    Comparison of time to positive serum CAA test between the vaccine and placebo groups after exposure to male Sm cercariae at week 12
    Time Frame
    week 12-24
    Title
    Peak CAA levels
    Description
    Comparison of peak serum CAA concentrations between the vaccine and placebo groups after exposure to male Sm cercariae at week 12
    Time Frame
    week 12-24
    Title
    Eosinophils
    Description
    Comparison of peak eosinophil counts between the vaccine and placebo groups after exposure to male Sm cercariae at week 12
    Time Frame
    week 12-24
    Title
    Antibody responses
    Description
    Comparison of (glycan) antibody responses directed against Sm antigens between the vaccine and placebo participants as well as between protected and non-protected participants after exposure to male Sm cercariae at week 12 using protein and glycan arrays
    Time Frame
    week 0-24
    Title
    Cellular responses
    Description
    Comparison of cellular responses directed against Sm antigens between the vaccine and placebo groups after immunisation and after controlled human infection with Sm cercariae, as well as between protected and non-protected participants
    Time Frame
    week 0-24
    Title
    In vitro killing
    Description
    Enumeration of the ability of Sm-p80-specific antibodies from human subjects to kill schistosome larvae in vitro from sera collected prior to each vaccination
    Time Frame
    week 0-24
    Title
    Transcriptomic profile
    Description
    Identification, characterization and comparison of gene expression changes as measured using RNA-seq analysis from PBMC between placebo and vaccine groups
    Time Frame
    week 0-24

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    45 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: Subject is aged ≥ 18 and ≤ 45 years and in good health. Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby. Subject is able to communicate well with the investigator, is available to attend all study visits. Subject will not travel to Schistosoma-endemic countries up until treatment at week 24. Subject agrees to refrain from blood and plasma donation to Sanquin or for other purposes throughout the study period. For female subjects: subject agrees to use adequate contraception and not to breastfeed for the duration of study. Subject has signed informed consent. Exclusion Criteria: Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine, malignant, haematological, infectious, immune-deficient, (severe) psychiatric and other disorders, which could compromise the health of the participant during the study or interfere with the interpretation of the study results. These include, but are not limited to, any of the following: body weight <50 kg or Body Mass Index (BMI) <18.0 or >35.0 kg/m2 at screening; positive HIV, HBV or HCV screening tests; the use of immune modifying drugs within three months prior to study onset (inhaled and topical corticosteroids and oral anti-histamines exempted) or expected use of such during the study period; history of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years; any history of treatment for severe psychiatric disease by a psychiatrist in the past year; history of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset. The chronic use of any drug known to interact with praziquantel, artesunate or lumefantrine metabolism (e.g. phenytoïn, carbamazepine, phenobarbital, primidon, dexamethason, rifampicine, cimetidine, flecaïnide, metoprolol, imipramine, amitriptyline, clomipramine, class IA and III anti-arrythmics, antipsychotics, antidepressants, macrolides, fluorchinolones, imidazole- and triazole antimycotics, antihistamines). Because lumefantrine may cause extension of QT-time, chronic use of drugs with effect on QT interval will result in exclusion from study participation. Any planned vaccination within 28 days before the start of the trial until the end of the immunisation phase (week 12), with the exception of SARS-CoV-2 vaccines or influenza vaccines. For female subjects: positive serum pregnancy test on the day before first immunisation. Any history of schistosomiasis or treatment for schistosomiasis. Positive serology for schistosomiasis or elevated serum CAA at screening. Known hypersensitivity to or contra-indications (including co-medication) for use of praziquantel, artesunate or lumefantrine. Being an employee or student of the department of Parasitology or Infectious diseases of the LUMC.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Meta Roestenberg, Prof
    Phone
    +31715269111
    Email
    M.Roestenberg@lumc.nl
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Meta Roestenberg, Prof
    Organizational Affiliation
    LUMC
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

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