Controlled Human Malaria Infection Model for Evaluation of Transmission-Blocking Interventions - Study 1

NCT02836002 | Completed Phase 1 DMC

• 1 other identifier: CHMI-trans1
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 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.

Conditions

Malaria

Outcome Measures

Primary Outcomes (2)

• Frequency and magnitude of adverse events in the CHMI-trans model in study groups

  Frequency and magnitude of adverse events in the CHMI-trans model in study groups.

  up to day 42 after challenge infection

• gametocyte prevalence

  Prevalence of gametocytes in the CHMI-trans model in study groups.

  up to day 42 after challenge infection

Secondary Outcomes (3)

• peak density gametocytes

  up to day 42 after challenge infection

• AUC gametocytes

  up to day 42 after challenge infection

• Gametocyte sex-ratio

  up to day 42 after challenge infection

Study Arms (4)

Group 1 - SP low/SP high

EXPERIMENTAL

Group 1 will be treated with a course of subcurative sulfadoxine-pyrimethamine (SP) (SP low, 500mg/25mg) as treatment 1. As treatment 2 (SP high) volunteers will receive a treatment with sulfadoxine-pyrimethamine (1000mg/50mg). Group 1 will receive a malaria challenge infection, P. falciparum 3D7 -infected mosquito bites Final treatment with a curative regimen of atovaquone/proguanil (malarone).

Drug: Sulfadoxine-pyrimethamine (low dose); Drug: Sulfadoxine-pyrimethamine (high dose); Biological: malaria challenge infection, P. falciparum 3D7; Drug: Atovaquone-proguanil

Group 2 - SP low/Pip high

EXPERIMENTAL

Group 2 will be treated with a course of subcurative sulfadoxine-pyrimethamine (SP) (SP low, 500mg/25mg) as treatment 1. As treatment 2 (Pip high) volunteers will receive a treatment with piperaquine (960mg). Group 2 will receive a malaria challenge infection, P. falciparum 3D7 -infected mosquito bites Final treatment with a curative regimen of atovaquone/proguanil (malarone).

Drug: Sulfadoxine-pyrimethamine (low dose); Drug: Piperaquine (high dose); Biological: malaria challenge infection, P. falciparum 3D7; Drug: Atovaquone-proguanil

Group 3 - Pip low/Pip high

EXPERIMENTAL

Group 3 will receive piperaquine (Pip) in a low-dose (Pip low, 480 mg) as treatment 1. As treatment 2 (Pip high) volunteers will receive a treatment with piperaquine (960mg). Group 3 will receive a malaria challenge infection, P. falciparum 3D7 -infected mosquito bites Final treatment with a curative regimen of atovaquone/proguanil (malarone).

Drug: Piperaquine (low dose); Drug: Piperaquine (high dose); Biological: malaria challenge infection, P. falciparum 3D7; Drug: Atovaquone-proguanil

Group 4 - Pip low/SP high

EXPERIMENTAL

Group 4 will receive piperaquine (Pip) in a low-dose (Pip low, 480 mg) as treatment 1. As treatment 2 (SP high) volunteers will receive a treatment with sulfadoxine-pyrimethamine (1000mg/50mg). Group 4 will receive a malaria challenge infection, P. falciparum 3D7 -infected mosquito bites Final treatment with a curative regimen of atovaquone/proguanil (malarone).

Drug: Piperaquine (low dose); Drug: Sulfadoxine-pyrimethamine (high dose); Biological: malaria challenge infection, P. falciparum 3D7; Drug: Atovaquone-proguanil

Interventions

Sulfadoxine-pyrimethamine (low dose) DRUG

\- subcurative regimen (500mg/25mg)

Also known as: Fansidar

Group 1 - SP low/SP high; Group 2 - SP low/Pip high

Piperaquine (low dose) DRUG

\- subcurative regimen (480 mg)

Also known as: piperaquine phosphate

Group 3 - Pip low/Pip high; Group 4 - Pip low/SP high

Sulfadoxine-pyrimethamine (high dose) DRUG

\- curative regimen (1000mg/50mg)

Also known as: Fansidar

Group 1 - SP low/SP high; Group 4 - Pip low/SP high

Piperaquine (high dose) DRUG

\- curative regimen (960 mg)

Also known as: piperaquine phosphate

Group 2 - SP low/Pip high; Group 3 - Pip low/Pip high

malaria challenge infection, P. falciparum 3D7 BIOLOGICAL

malaria challenge infection by P. falciparum 3D7-infected mosquito bites

Also known as: 3D7 Plasmodium falciparum

Group 1 - SP low/SP high; Group 2 - SP low/Pip high; Group 3 - Pip low/Pip high; Group 4 - Pip low/SP high

Atovaquone-proguanil DRUG

\- curative regimen: 1000/400 mg, for 3 days

Also known as: Malarone

Group 1 - SP low/SP high; Group 2 - SP low/Pip high; Group 3 - Pip low/Pip high; Group 4 - Pip low/SP high

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

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 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).
• 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 subjects usual daily activity or exercise routine) during the malaria challenge period.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead
• The PATH Malaria Vaccine Initiative (MVI): collaborator
• QIMR Berghofer Medical Research Institute: collaborator

Study Sites (1)

Radboud university medical center

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Related Publications (2)

• Reuling IJ, van de Schans LA, Coffeng LE, Lanke K, Meerstein-Kessel L, Graumans W, van Gemert GJ, Teelen K, Siebelink-Stoter R, van de Vegte-Bolmer M, de Mast Q, van der Ven AJ, Ivinson K, Hermsen CC, de Vlas S, Bradley J, Collins KA, Ockenhouse CF, McCarthy J, Sauerwein RW, Bousema T. A randomized feasibility trial comparing four antimalarial drug regimens to induce Plasmodium falciparum gametocytemia in the controlled human malaria infection model. Elife. 2018 Feb 27;7:e31549. doi: 10.7554/eLife.31549.

  PMID: 29482720 RESULT

• Post A, Kabore B, Reuling IJ, Bognini J, van der Heijden W, Diallo S, Lompo P, Kam B, Herssens N, Lanke K, Bousema T, Sauerwein RW, Tinto H, Jacobs J, de Mast Q, van der Ven AJ. The XN-30 hematology analyzer for rapid sensitive detection of malaria: a diagnostic accuracy study. BMC Med. 2019 May 31;17(1):103. doi: 10.1186/s12916-019-1334-5.

  PMID: 31146732 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

fanasil, pyrimethamine drug combination; piperaquine; atovaquone, proguanil drug combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2016
• First Posted: July 18, 2016
• Study Start: June 1, 2016
• Primary Completion: June 29, 2017
• Study Completion: June 29, 2017
• Last Updated: March 23, 2018

Record last verified: 2017-09

Locations

NL (1)