Sm-p80 Schistosomiasis Challenge Study

Study Overview
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Brief Summary
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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.

Official Title
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Safety and Preliminary Efficacy of Sm-p80 + GLA-SE (SchistoShield®) Vaccine Against Controlled Human Schistosome Infection in Healthy, Schistosoma-naïve Adults

Conditions
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Schistosoma Mansoni, Schistosomiasis

Intervention / Treatment
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* Biological: Sm-p80 + GLA-SE Vaccine
* Other: Placebo
* Biological: Schistosoma mansoni infection


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaccine group<br>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. | Biological: Sm-p80 + GLA-SE Vaccine<br>* 30 μg Sm-p80 + 5 μg GLA-SE<br>Biological: Schistosoma mansoni infection<br>* 20 viable male Schistosoma mansoni cercariae of the Puerto Rican strain<br>|
| Placebo Comparator: Placebo control group<br>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. | Other: Placebo<br>* 0.9% Sterile Normal Saline<br>Biological: Schistosoma mansoni infection<br>* 20 viable male Schistosoma mansoni cercariae of the Puerto Rican strain<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | week 12-24, i.e. after challenge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of (repeated) immunisation | Frequency and severity of adverse events after (repeated) immunisation with Sm-p80 + GLA-SE | week 0-12 | 
| Immunogenicity | Anti-Sm-p80 IgG antibody titres after (repeated) immunisation with Sm-p80 + GLA-SE measured by ELISA | week 0-24 |