Primary Objective: - To investigate the safety, tolerability and attack rate of female Schistosoma mansoni cercariae in healthy Schistosome-naïve volunteers Exploratory Objectives: - To investigate the kinetics of circulating anodic antigen (CAA)…
ID
Source
Brief title
Condition
- Helminthic disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameter/endpoint:
• Frequency and severity of adverse events after controlled human Schistosoma
mansoni infection with female cercariae.
• The number of female cercariae at which 100% volunteers show detectable
Schistosoma mansoni circulating anodic antigen
Secondary outcome
Other study parameters/endpoints:
• Time to positive serum and urine CAA test
• Comparison of the peak serum CAA concentration in different dose groups
• Humoral (antibody) response directed against Sm antigens
• Cellular responses directed against Sm antigens
• Changes in microbiome after controlled human Schistosoma mansoni infection
with female 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. Previously, we have established
a male-only controlled human Schistosoma mansoni infection model, that proved
to be safe and well-tolerated in healthy Schistosoma-naïve healthy volunteers.
In this study we aim to develop a female-only controlled human Schistosoma
mansoni infection model that can be used to provide early proof-of-concept data
on candidate schistosomiasis vaccines and serve as a platform to study
schistosome immune responses. This is of particular relevance as one of the
developed schistosomiasis vaccine candidate*s target antigens is preferentially
expressed on female schistosomes.
Study objective
Primary Objective:
- To investigate the safety, tolerability and attack rate of female Schistosoma
mansoni cercariae in healthy Schistosome-naïve volunteers
Exploratory Objectives:
- To investigate the kinetics of circulating anodic antigen (CAA) after
infection with female Schistosoma mansoni cercariae in healthy
Schistosome-naïve volunteers
- To investigate immunological, metabolic and microbiome changes after
infection with Schistosoma mansoni female cercariae
- To explore potential differences in CAA kinetics and immunological responses
after infection with male or female Schistosoma mansoni cercariae
Study design
Open label, dose escalation intervention study with adaptive design
Intervention
Groups of 3 or 7 volunteers will be exposed to a pre-defined number of female
cercariae. Depending on the outcome of infection and safety data, the dose will
be escalated 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 16
weeks. After this bi-weekly visits will follow until week 20. Final follow up
visit will be after one year. Blood and urine sampling will take place at every
visit. Nasosorption sampling is performed during the first eight weeks. They
will keep a diary to record adverse events during 20 weeks. Volunteers will be
dermally exposed to female cercariae once. They may experience adverse events,
related to acute schistosomiasis syndrome with fatigue, malaise, and fever. At
8 weeks and 12 weeks after infection, they will be treated with praziquantel to
cure the Schistosoma infection. Praziquantel is known to potentially give
fatigue, gastrointestinal side effects, and dizziness. 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 8 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.
2. The chronic use of any drug known to interact with praziquantel, 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 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
Design
Recruitment
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 | NCT04269915 |
| CCMO | NL72661.058.20 |