Controlled Human Malaria Infection Model for Evaluation of Transmission-blocking Interventions - Study 2
CHMI-trans2
1 other identifier
interventional
24
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable
Started May 2018
Shorter than P25 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 27, 2018
CompletedFirst Posted
Study publicly available on registry
March 5, 2018
CompletedStudy Start
First participant enrolled
May 7, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
November 20, 2018
CompletedResults Posted
Study results publicly available
March 31, 2020
CompletedJuly 7, 2020
March 1, 2020
6 months
February 27, 2018
November 6, 2019
June 15, 2020
Conditions
Outcome Measures
Primary Outcomes (3)
Frequency of Adverse Events in the CHMI-trans Model
Frequency of adverse events in the CHMI-trans model.
up to day 51 after challenge infection
Gametocyte Prevalence
Number of individuals in each study arm that show prevalence of gametocytes as defined by quantitative reverse-transcriptase PCR (qRT-PCR) for CCp4 (female) and PfMGET (male) mRNA with a threshold of 5 gametocytes/mL for positivity.
up to day 51 after challenge infection
Magnitude of Adverse Events in the CHMI-trans Model
symptoms will be ranked as (1) mild, (2) moderate, or (3) severe, depending on their intensity according to the following scale: * Mild (grade 1): awareness of symptoms that are easily tolerated and do not interfere with usual daily activity * Moderate (grade 2): discomfort that interferes with or limits usual daily activity * Severe (grade 3): disabling, with subsequent inability to perform usual daily activity, resulting in absence or required bed rest
up to day 51 after challenge infection
Secondary Outcomes (5)
Peak Density Gametocytes
up to day 51 after challenge infection
AUC Gametocytes
up to day 51 after challenge infection
Gametocyte Commitment
up to day 51 after challenge infection
Gametocyte Sex-ratio
up to day 51 after challenge infection
Number of Participants Infectious for Mosquitoes Through DFA
up to day 51 after challenge infection
Study Arms (4)
Group 1 (Cohort A) LD-PIP/LD-PIP2/PIP
EXPERIMENTALCohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 1 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg).
Group 2 (Cohort A) LD-PIP/LD-PIP2/SP
EXPERIMENTALCohort A will be subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 2(LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Group 3 (Cohort B) LD-PIP/LD-PIP2/PIP
EXPERIMENTALCohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 3 (LD-PIP/LD-PIP2/PIP) will be curatively treated with piperaquine (960mg)
Group 4 (Cohort B) LD-PIP/LD-PIP2/SP
EXPERIMENTALCohort B will be subjected to a standard blood stage challenge with \~2,800 Pf-infected erythrocytes by intravenous injection. All volunteers will be treated with a single oral subcurative low-dose of piperaquine (LD-PIP, 480 mg, T1). Volunteers will receive a second treatment (T2, LD-PIP2, 480mg) if a recrudescence of asexual parasitemia occurs before day 21 post challenge infection. Volunteers in group 4 (LD-PIP/LD-PIP2/SP) will be curatively treated with sulfadoxine-pyrimethamine (1000mg/50mg).
Interventions
subcurative regimen (480 mg)
Curative regimen (960mg)
Curative regimen (1000mg/50mg)
Curative regimen (1000/400 mg, for 3 days)
malaria challenge infection by P. falciparum 3D7-infected mosquito bites
P. falciparum 3D7-infected human erythrocytes administered intravenously for the purpose controlled human malaria infection.
Eligibility Criteria
You may qualify if:
- In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Subject is aged ≥ 18 and ≤ 35 years and in good health.
- 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.
- Subject is willing to complete an informed consent questionnaire and is able to answer all questions correctly.
- 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).
- 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.
- 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.
- 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.
- For female subjects: subject agrees to use continuous adequate contraception\*\* and not to breastfeed for the duration of study.
- 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.
- Subject agrees to avoid additional triggers that may cause elevations in liver enzymes including alcohol from baseline up to 1 week post treatment (T3).
- 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.)
You may not qualify if:
- A potential subject who meets any of the following criteria will be excluded from participation in this study:
- 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.
- 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.
- A medical history of functional asplenia, sickle cell trait/disease, thalassaemia trait/disease or G6PD-deficiency.
- History of epilepsy in the period of five years prior to study onset, even if no longer on medication.
- 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.
- 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).
- 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.
- For female subjects: positive urine pregnancy test at screening and/or at the baseline visit.
- Abnormal ALT/AST values on baseline
- Any history of malaria, positive serology for P. falciparum, or previous participation in any malaria (vaccine) study.
- 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.
- Participation in any other clinical study in the 30 days prior to the start of the study or during the study period.
- Being an employee or student of the department of Medical Microbiology of the Radboudumc or the department of Internal Medicine.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Radboud university medical center
Nijmegen, Gelderland, 6525 GA, Netherlands
Related Publications (1)
Alkema M, Reuling IJ, de Jong GM, Lanke K, Coffeng LE, van Gemert GJ, van de Vegte-Bolmer M, de Mast Q, van Crevel R, Ivinson K, Ockenhouse CF, McCarthy JS, Sauerwein R, Collins KA, Bousema T. A Randomized Clinical Trial to Compare Plasmodium falciparum Gametocytemia and Infectivity After Blood-Stage or Mosquito Bite-Induced Controlled Malaria Infection. J Infect Dis. 2021 Oct 13;224(7):1257-1265. doi: 10.1093/infdis/jiaa157.
PMID: 32239171RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Prof. dr. Teun Bousema
- Organization
- Radboud university medical center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- OTHER
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Prof. dr.
Study Record Dates
First Submitted
February 27, 2018
First Posted
March 5, 2018
Study Start
May 7, 2018
Primary Completion
November 1, 2018
Study Completion
November 20, 2018
Last Updated
July 7, 2020
Results First Posted
March 31, 2020
Record last verified: 2020-03