Single-sex Controlled Human Schistosomiasis Infection: Safety and Dose Finding

Establishing a Single-sex Controlled Human Schistosomiasis Infection Model: Safety and Dose Finding

Groups of 3 or 7 volunteers will be exposed to a predetermined number of male Schistosoma mansoni cercariae until 10 volunteers are found infected.

Study Overview

• Status: Completed
• Conditions: Schistosomiasis; Schistosoma Mansoni
• Intervention / Treatment: Biological: male Schistosoma mansoni cercariae

• Study Type: Interventional
• Enrollment (Actual): 17
• 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 and is reachable by mobile telephone from week 3 to week 12 of the study period.
5. Subject agrees to refrain from blood donation 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, 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 >30.0 kg/m2 at screening;
   • positive HIV, hepatitis B or hepatitis C 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.
   • Any clinically significant abnormalities (including extended QT interval) on electrocardiogram
2. The chronic use of any drug known to interact with praziquantel, or artesunate or lumefantrine metabolism (e.g. phenytoin, carbamazepine, phenobarbital, primidon, dexamethasone, rifampicin, cimetidine, flecainide, metoprolol, imipramine, amitriptyline, clomipramine, class I 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 are excluded from the study.
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 or urine circulating anodic antigen or positive Schistosoma serology at baseline.
6. Known hypersensitivity to or contra-indications (including co-medication) for use of praziquantel or, artesunate or lumefantrine.
7. Being an employee or student of the department of parasitology or infectious diseases of the Leiden University Medical Center.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Volunteers will be exposed to escalating doses of male Schistosoma mansoni cercariae	Biological: male Schistosoma mansoni cercariae; Viable male Schistosoma mansoni cercariae of the Puerto Rican strain

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of grade 3 and 4 adverse events, possibly, probably or definitely related to controlled human Schistosoma mansoni infection with male cercariae.	20 weeks
The number of male cercariae at which 100% volunteers show detectable Schistosoma mansoni circulating anodic antigen (CAA).	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Average number of weeks until positive serum circulating anodic antigen test	12 weeks
Comparison of the height of the peak serum circulating anodic antigen concentration in low dose compared with high dose group	12 weeks
Comparison of the humoral (antibody) response profile by protein and glycan array between infected and uninfected individuals	1 year
Differences in in ex vivo lymphocyte profiles between infected and uninfected individuals	1 year

Collaborators and Investigators

• Sponsor: Leiden University
• Investigators: Principal Investigator: Meta Roestenberg, LUMC

Publications and helpful links

General Publications

• Langenberg MCC, Hoogerwerf MA, Janse JJ, van Lieshout L, Corstjens PLAM, Roestenberg M; CoHSI clinical trial team. Katayama Syndrome Without Schistosoma mansoni Eggs. Ann Intern Med. 2019 May 21;170(10):732-733. doi: 10.7326/L18-0438. Epub 2019 Jan 8. No abstract available.
• Langenberg MCC, Hoogerwerf MA, Koopman JPR, Janse JJ, Kos-van Oosterhoud J, Feijt C, Jochems SP, de Dood CJ, van Schuijlenburg R, Ozir-Fazalalikhan A, Manurung MD, Sartono E, van der Beek MT, Winkel BMF, Verbeek-Menken PH, Stam KA, van Leeuwen FWB, Meij P, van Diepen A, van Lieshout L, van Dam GJ, Corstjens PLAM, Hokke CH, Yazdanbakhsh M, Visser LG, Roestenberg M. A controlled human Schistosoma mansoni infection model to advance novel drugs, vaccines and diagnostics. Nat Med. 2020 Mar;26(3):326-332. doi: 10.1038/s41591-020-0759-x. Epub 2020 Feb 17.

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2016
• Primary Completion (Actual): July 19, 2018
• Study Completion (Actual): January 21, 2019

Study Registration Dates

• First Submitted: April 25, 2016
• First Submitted That Met QC Criteria: April 27, 2016
• First Posted (Estimate): April 28, 2016

Study Record Updates

• Last Update Posted (Actual): November 18, 2020
• Last Update Submitted That Met QC Criteria: November 16, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Helminthiasis; Trematode Infections; Schistosomiasis
• Other Study ID Numbers: CoHSI1

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