Primary objective: To investigate the safety, tolerability and infectivity of male Schistosoma mansoni cercariae in healthy Schistosoma-naïve volunteers. Exploratory objectives: To investigate the kinetics of controlled infection with male…
ID
Source
Brief title
Condition
- Helminthic disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Frequency and magnitude of adverse events after controlled human Schistosoma
mansoni infection with male cercariae.
- The number of male cercariae at which 100% volunteers show detectable
Schistosoma mansoni circulating anodic antigen.
Secondary outcome
- Time to positive serum and urine CAA (Circulating Anodic Antigen) test;
- Comparison of the height of the peak serum CAA concentration in different
dose groups.
- Humoral (antibody) responses directed against Sm antigens
- Cellular responses directed against Sm antigens
- Changes in microbiome after controlled human Schistosoma mansoni infection
with male Sm cercariae.
Background summary
Schistosomiasis is a parasitic disease of global importance, for which no
vaccine exists. Vaccine candidates are tested for efficacy in large-scale Phase
2 and 3 field trials in Schistosoma-endemic areas, where the endpoint is
usually the incidence of infection or disease following natural exposure. Such
trials therefore require long duration and/or large population sizes in order
to obtain a good estimate of the effect size. Conducting controlled,
experimental infection studies have been shown to eliminate several drawbacks
of the traditional proof-of-efficacy approach. This study thus aims to develop
a novel controlled human schistosomiasis infection model that can be used to
provide early proof-of-concept data on candidate schistosomiasis vaccines and
are an innovative approach to study schistosome immune responses.
Study objective
Primary objective:
To investigate the safety, tolerability and infectivity of male Schistosoma
mansoni cercariae in healthy Schistosoma-naïve volunteers.
Exploratory objectives:
To investigate the kinetics of controlled infection with male Schistosoma
mansoni cercariae in healthy Schistosoma-naïve volunteers.
To investigate immunological, metabolic and microbiome changes after infection
with Schistosoma mansoni male cercariae.
Study design
Open label intervention study
Intervention
Groups of 3 or 7 volunteers will be exposed to 10, 30 and 20 cercariae.
Depending on the outcome of infection, the dose will be adapted or additional
volunteers will be exposed to the same number of cercariae. Volunteers will
visit the clinical trial centre weekly after infection to record adverse
events.
Study burden and risks
Volunteers will be requested to visit the trial centre on a weekly basis for 12
weeks. After this bi-weekly visits will follow until week 24. Final follow up
visit will be after one year. Blood and urine sampling will take place at every
visit. They will keep a diary to register adverse events during 24 weeks.
Volunteers will be dermally exposed to single-sex cercariae once. They may
experience adverse events, such as malaise, fatigue or Katayama fever. Twelve
weeks after infection, they will be treated with praziquantel to cure the
Schistosoma infection, which is known to give gastrointestinal side effects.
Praziquantel may be repeated at 18 weeks. There is no benefit to participation
in the trial.
Albinusdreef 2
Leiden 2333ZA
NL
Albinusdreef 2
Leiden 2333ZA
NL
Listed location countries
Age
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 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, 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, 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.
- 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. 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 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 CAA 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 LUMC.
Design
Recruitment
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02755324 |
| CCMO | NL57697.058.16 |