Repeated Controlled Human Schistosoma Mansoni Infection

Schistosomiasis Clinical Trial

Official title:

Safety and Protective Efficacy of Repeated Controlled Human Schistosoma Mansoni Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05085470
• Other study ID #: ReCoHSI
• Status: Completed
• Phase: N/A
• Start date: October 29, 2021
• Est. completion date: January 11, 2023

Study information

• Verified date: January 2023
• Source: Leiden University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: January 11, 2023
• Est. primary completion date: January 11, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Schistosoma Mansoni
• Schistosomiasis
• Schistosomiasis mansoni

Intervention

Biological:
• Schistosoma mansoni infection
20 viable male Schistosoma mansoni cercariae of the Puerto Rican strain
• Placebo mock infection
Placebo mock infection with water

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Center	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
Leiden University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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