NCT02836002

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

'Controlled Human Malaria Infection Study to Assess Gametocytaemia and Mosquito Transmissibility in Participants Challenged With Plasmodium Falciparum by Sporozoite Challenge to Establish a Model for the Evaluation of Transmission-blocking Interventions'

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 29 (actual)
• Sponsor: Radboud University Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 35 Years
• Healthy volunteers: Accepted

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.

Detailed description

A total of 32 volunteers will be randomly assigned to four groups (n=8) and subjected to a standard controlled human malaria infection (CHMI) delivered by five Pf-infected mosquitoes (3D7 clone). Treatment is subsequently initiated to induce gametocytaemia (treatment 1, DT1) and to clear pathogenic asexual parasites whilst leaving gametocytes unaffected (treatment 2, DT2). At the end of the study, treatment of all parasite stages is provided following national treatment guidelines (end treatment, ET). Once malaria infections are detected by 18S qPCR positive (day of treatment 1 \[DT1\]), groups 1 and 2 will be treated with a course of subcurative sulfadoxine-pyrimethamine (SP) (SP low, 500mg/25mg). Groups 3 and 4 will receive piperaquine (Pip) in a low-dose (Pip low, 480 mg). After DT1, volunteers will receive a curative treatment (DT2) when a recrudescence of asexual parasitaemia occurs or on day 21 post challenge infection, whichever comes first. Volunteers in group 1 (SP low/SP high) will be treated with sulfadoxine-pyrimethamine (1000mg/50mg) and group 2 (SP low/Pip high) with piperaquine (960mg). Volunteers in group 3 (Pip low/Pip high) will be treated with piperaquine (960mg) and group 4 (Pip low/SP high) with sulfadoxine-pyrimethamine (1000mg/50mg). To ensure the radical clearance of all parasite stages, all volunteers will receive a final treatment (ET) according to national guidelines with atovaquone/proguanil (Malarone®) on day 42. Daily blood samples will allow detailed quantification of gametocytes, gametocyte sex ratio and ex vivo assessments of gametocyte fitness.

Conditions

• Malaria

Interventions

Type	Name	Description
DRUG	Sulfadoxine-pyrimethamine (low dose)	\- subcurative regimen (500mg/25mg)
DRUG	Piperaquine (low dose)	\- subcurative regimen (480 mg)
DRUG	Sulfadoxine-pyrimethamine (high dose)	\- curative regimen (1000mg/50mg)
DRUG	Piperaquine (high dose)	\- curative regimen (960 mg)
BIOLOGICAL	malaria challenge infection, P. falciparum 3D7	malaria challenge infection by P. falciparum 3D7-infected mosquito bites
DRUG	Atovaquone-proguanil	\- curative regimen: 1000/400 mg, for 3 days

Timeline

• Start date: 2016-06-01
• Primary completion: 2017-06-29
• Completion: 2017-06-29
• First posted: 2016-07-18
• Last updated: 2018-03-23

Locations

1 site across 1 country: Netherlands