Clinical trial NCT05085470: Repeated Controlled Human Schistosoma Mansoni Infection
Official title: Safety and Protective Efficacy of Repeated Controlled Human Schistosoma Mansoni Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schistosomiasis
Schistosoma Mansoni
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
First posted: 2021-10-20
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: A group of 24 healthy volunteers are challenged one or three times with 20 male Schistosoma mansoni cercariae to investigate whether this leads to protection and to identify potential correlates of protection


Eligibility criteria: Inclusion Criteria:

1. Subject is aged ≥ 18 and ≤ 45 years and in good health.
2. Subject has adequate understanding of the procedures of the study and agrees to abide strictly thereby.
3. Subject is able to communicate well with the investigator, is available to attend all study visits.
4. Subject will remain within Europe (excluding Corsica) during the study period.
5. Subject agrees to refrain from blood and plasma donation to Sanquin or for other purposes throughout the study period.
6. For female subjects: subject agrees to use adequate contraception and not to breastfeed for the duration of study.
7. Subject has signed informed consent.

Exclusion Criteria:

1. 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 volunteer 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, hepatitis B virus or hepatitis C virus 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.
2. The chronic use of any drug known to interact with praziquantel, artesunate or lumefantrine metabolism (e.g. phenytoin, carbamazepine, phenobarbital, primidone, dexamethasone, rifampicin, cimetidine, flecainide, metoprolol, imipramine, amitriptyline, clomipramine, class IA and III anti-arrythmics, antipsychotics, antidepressants, macrolides, fluoroquinolones, 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.
3. For female subjects: positive urine pregnancy test at screening.
4. Any history of schistosomiasis or treatment for schistosomiasis.
5. Positive serology for schistosomiasis or elevated serum CAA at screening.
6. Known hypersensitivity to or contra-indications (including co-medication) for use of praziquantel, artesunate or lumefantrine.
7. Being an employee or student of the department of Parasitology or Infectious diseases of the LUMC.

Primary outcomes:
measure: Protective efficacy
timeFrame: From week 18 until week 30
measure: Safety of (repeated) exposure to male Sm cercariae based on self-reported adverse events
timeFrame: 38 weeks
Secondary outcomes:
measure: Time to CAA positivity
timeFrame: From week 18 until week 30
measure: Peak serum CAA levels
timeFrame: From week 18 until week 30
measure: Eosinophils
timeFrame: From week 18 until week 30
measure: Antibody responses
timeFrame: From week 18 until week 30
measure: Cellular responses
timeFrame: From week 18 until week 30
measure: Attack rate
timeFrame: 26 weeks
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
Study officials:
References: