Controlled Human Malaria Infection model for evaluation of transmission-blocking interventions – Study 1

Phase 1

• Conditions: Plasmodium falciparum malaria; MedDRA version: 19.0Level: PTClassification code 10070881Term: Malaria antibody test positiveSystem Organ Class: 10022891 - Investigations; MedDRA version: 19.0Level: LLTClassification code 10016171Term: Falciparum malariaSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Parasitic Diseases [C03]

• Registration Number: EUCTR2016-001379-66-NL
• Lead Sponsor: Radboud university medical center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-05-04
• Last Update Posted: 19 November 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

In order to be eligible to participate in this study, a subject must meet all of the following criteria:
1.Subject is aged = 18 and = 35 years and in good health.
2.Subject has adequate understanding of the procedures of the study and is able and willing (in the investigator’s opinion) to comply with all study requirements.
3.Subject is willing to complete an informed consent questionnaire and is able to answer all questions correctly.
4.Subject is able to communicate well with the investigator and is available to attend all study visits, lives in proximity to the trial centre (<10 km) or (if >10km) is willing to stay in a hotel close to the trial centre during part of the study (from day 5 post-infection until DT1+4 provided that the subject has had 2 consecutive negative 18S qPCR tests (at least 24 hours apart) following DT1 treatment; or until day DT2+3).
5.The subject will remain within the Netherlands during the challenge period, will not travel to a malaria-endemic area during the study period, and is reachable (24/7) by mobile telephone throughout the entire study period.
6.Subject agrees to their general practitioner being informed and contacted about their participation in the study and agrees to sign a form to request the release by their General Practitioner (GP), and medical specialist when necessary, to the investigator(s), of any relevant medical information concerning possible contra-indications for participation in the study.
7.The subject agrees to refrain from blood donation to Sanquin or for other purposes throughout the study period and for a defined period thereafter according to current Sanquin guidelines.
8.For female subjects: subject agrees to use continuous adequate contraception** and not to breastfeed for the duration of study.
9.Subject agrees to refrain from intensive physical exercise (disproportionate to the subjects usual daily activity or exercise routine) during the malaria challenge period.
10.Subject has signed written informed consent to participate in the trial.

(*Acceptable forms of contraception include: established use of oral, injected or implanted hormonal contraceptives; intrauterine device or intrauterine system; barrier methods (condoms or diaphragm with additional spermicide); male partner’s sterilisation (with appropriate post-vasectomy documentation of absence of sperm in the ejaculate); true abstinence when this is in line with the preferred and usual lifestyle of the subject; Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 32
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded from participation in this study:
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, immunodeficient, 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.
1.1.Body weight <50 kg or Body Mass Index (BMI) <18 or >30 kg/m2 at screening.
1.2.A heightened risk of cardiovascular disease, as determined by: an estimated ten year risk of fatal cardiovascular disease of =5% at screening, as determined by the Systematic Coronary Risk Evaluation (SCORE); history, or evidence at screening, of clinically significant arrhythmia’s, prolonged QT-interval or other clinically relevant ECG abnormalities; or a positive family history of cardiac events in 1st or 2nd degree relatives <50 years old.
1.3.A medical history of functional asplenia, sickle cell trait/disease, thalassaemia trait/disease or G6PD-deficiency.
1.4.History of epilepsy in the period of five years prior to study onset, even if no longer on medication.
1.5.Screening tests positive for Human Immunodeficiency Virus (HIV), active Hepatitis B Virus (HBV), Hepatitis C Virus (HCV)
1.6.Chronic use of i) immunosuppressive drugs, ii) antibiotics, iii) or other 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.
1.7.Any recent or current systemic therapy with an antibiotic or drug with potential anti-malarial activity (chloroquine, doxycycline, tetracycline, piperaquine, benzodiazepine, flunarizine, fluoxetine, tetracycline, azithromycin, clindamycin, erythromycin, hydroxychloroquine, etc.) (allowable timeframe for use at the Investigator’s discretion).
1.8.History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years.
1.9.Any history of treatment for severe psychiatric disease by a psychiatrist in the past year.
1.10.History of drug or alcohol abuse interfering with normal social function in the period of one year prior to study onset, positive urine toxicology test for cocaine or amphetamines at screening or at inclusion, or positive urine toxicology test for cannabis at inclusion.

2.For female subjects: positive urine pregnancy test at screening and/or at the baseline visit.
3.Any history of malaria, positive serology for P. falciparum, or previous participation in any malaria (vaccine) study.
4.Known hypersensitivity to or contra-indications (including co-medication) for use of sulfadoxine-pyrimethamine, piperaquine, chloroquine, Malarone, artemether-lumefantrine, primaquine or history of severe (allergic) reactions to mosquito bites.
5.Participation in any other clinical study in the 30 days prior to the start of the study or during the study period.
6.Being an employee or student of the department of Medical Microbiology of the Radboudumc or the department of Internal Medicine.
7.Any other condition or situation that would, in the opinion of the investigator

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: - To evaluate the safety of four different CHMI-trans protocols in healthy malaria-naïve volunteers challenged with Plasmodium falciparum by sporozoite challenge. <br>- To determine the best CHMI-trans protocol for induction of stable gametocytaemia at densities detectable by qRT-PCR <br>;Secondary Objective: - To determine the dynamics of gametocyte commitment, maturation and sex ratio by molecular markers of sexual stage development.<br>- To determine the peak density and time-point of peak density of gametocytaemia in the CHMI-trans model.<br>- To determine the area under the curve of gametocyte density versus time.<br>;Primary end point(s): - Frequency and magnitude of adverse events in the CHMI-trans model in study groups.<br>- Prevalence of gametocytes in the CHMI-trans model in study groups.<br>;Timepoint(s) of evaluation of this end point: Day 6 - day 40 after malaria challenge infection

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Peak density and time-point of peak density of gametocytes by qRT-PCR.<br>- The area under the curve of gametocyte density versus time. <br>- Assessment of the dynamics of gametocyte commitment, maturation and sex-ratio.<br>;Timepoint(s) of evaluation of this end point: Day 6 - day 40 after malaria challenge infection