Repeated Controlled Human Schistosoma Mansoni Infection

Safety and Protective Efficacy of Repeated Controlled Human Schistosoma Mansoni Infection

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

Study Overview

• Status: Completed
• Conditions: Schistosomiasis; Schistosoma Mansoni
• Intervention / Treatment: Biological: Schistosoma mansoni infection; Biological: Placebo mock infection

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Leiden University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Reinfection group; Participants will be exposed three times to 20 male Schistosoma mansoni cercariae (weeks 0, 9, and 18)	Biological: Schistosoma mansoni infection; 20 viable male Schistosoma mansoni cercariae of the Puerto Rican strain
Active Comparator: Infection control group; 12 participants who will undergo a placebo mock infection with water twice (weeks 0 and 9) and will be exposed once to 20 male Schistosoma mansoni cercariae (week 18)	Biological: Schistosoma mansoni infection; 20 viable male Schistosoma mansoni cercariae of the Puerto Rican strain; Biological: Placebo mock infection; Placebo mock infection with water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Protective efficacy	The protective efficacy of repeated exposure to male Sm cercariae measured by the difference in frequency of serum circulating aniodic antigen (CAA) positivity (≥1.0 pg/mL) between the reinfection group and the infection control group at any timepoint after the final infection at week 18 and before week 30	From week 18 until week 30
Safety of (repeated) exposure to male Sm cercariae based on self-reported adverse events	Frequency and severity of adverse events after (repeated) human Sm infection with male cercariae	38 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to CAA positivity	Comparison of time to positive serum and urine CAA test between the reinfection and infection control groups after the final infection at week 18 and before week 30	From week 18 until week 30
Peak serum CAA levels	Comparison of peak serum CAA concentration between the reinfection and infection control group after the final infection at week 18 and before week 30	From week 18 until week 30
Eosinophils	Comparison of eosinophil counts between the reinfection and infection control groups after challenge after the final infection at week 18 and before week 30	From week 18 until week 30
Antibody responses	Comparison of (glycan) antibody responses directed against Sm antigens between the reinfection and infection control participants as well as between protected and non-protected participants after the final infection at week 18 and before week 30 using protein and glycan arrays	From week 18 until week 30
Cellular responses	Comparison of cellular responses directed against Sm antigens between the reinfection and infection control participants as well as between protected and non-protected participants after the final infection at week 18 and before week 30 using flow cytometry	From week 18 until week 30
Attack rate	The pooled attack rate after initial exposure to 20 male cercariae, i.e. proportion CAA positivity between week 0-8 for the reinfection participants and between week 18-26 for infection control participants	26 weeks

Collaborators and Investigators

• Sponsor: Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2021
• Primary Completion (Actual): January 11, 2023
• Study Completion (Actual): January 11, 2023

Study Registration Dates

• First Submitted: August 6, 2021
• First Submitted That Met QC Criteria: October 18, 2021
• First Posted (Actual): October 20, 2021

Study Record Updates

• Last Update Posted (Estimate): January 30, 2023
• Last Update Submitted That Met QC Criteria: January 27, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Helminthiasis; Trematode Infections; Schistosomiasis; Schistosomiasis mansoni
• Other Study ID Numbers: ReCoHSI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No