Overview

Controlled Human Malaria Infection Model for Evaluation of Transmission-blocking Interventions - Study 2

Status:
Completed
Trial end date:
2018-11-20
Target enrollment:
0
Participant gender:
All
Summary
This is a single-center, open label study. The primary aim of this project is to develop a controlled human malaria infection transmission model ("CHMI-trans") or "challenge model" to evaluate the capacity of vaccines, biologics (monoclonal antibodies, or mAbs), and drugs to block malaria parasite transmission by assessing infectiousness of Plasmodium falciparum (Pf) gametocyte carriers for Anopheles mosquitoes.
Phase:
N/A
Accepts Healthy Volunteers?
Accepts Healthy Volunteers
Details
Lead Sponsor:
Radboud University
Collaborators:
QIMR Berghofer Medical Research Institute
The PATH Malaria Vaccine Initiative (MVI)
Treatments:
Atovaquone
Atovaquone, proguanil drug combination
Fanasil, pyrimethamine drug combination
Piperaquine
Proguanil
Pyrimethamine
Sulfadoxine
Criteria
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 4 (blood stage challenge) 5 (sporozoite challenge) post-infection until T1+4
provided that the subject has had 2 consecutive negative 18S qPCR tests (at least 24
hours apart) following T1 treatment; or until day T3+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
subject's usual daily activity or exercise routine) during the malaria challenge
period until day 38 after infection.

10. Subject agrees to avoid additional triggers that may cause elevations in liver enzymes
including alcohol from baseline up to 1 week post treatment (T3).

11. 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.)

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. Abnormal ALT/AST values on baseline

4. Any history of malaria, positive serology for P. falciparum, or previous participation
in any malaria (vaccine) study.

5. 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.

6. Participation in any other clinical study in the 30 days prior to the start of the
study or during the study period.

7. Being an employee or student of the department of Medical Microbiology of the
Radboudumc or the department of Internal Medicine.

8. Any other condition or situation that would, in the opinion of the investigator, place
the subject at an unacceptable risk of injury or render the subject unable to meet the
requirements of the protocol.

9. For cohort B (blood stage challenge): Received a blood transfusion in the past.

10. For cohort B (blood stage challenge): Women of childbearing potential with a screening
test positive for erythrocyte anti-Rh(c) and/or anti-Rh(e) antibodies.