NCT03813108

Safety and Efficacy of NF135 CPS Immunization

Safety and Protective Efficacy of Chemoprophylaxis and Sporozoite Immunization With Plasmodium Falciparum NF135 Against Homologous and Heterologous Challenge Infection in Healthy Volunteers in the Netherlands

• Status: Terminated
• Phase: N/A
• Study type: Interventional
• Enrollment: 43 (actual)
• Sponsor: Radboud University Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 35 Years
• Healthy volunteers: Accepted

Summary

This is an open label, randomized, controlled clinical trial. The primary aim of this project is to determine the safety and tolerability of NF135.C10 sporozoite immunization under chemoprophylaxis against homologous and heterologous challenge infection.

Detailed description

A total of 49 healthy volunteers will be allocated to receive either three immunizations with 15 NF135.C10 infected Anopheles mosquitoes (n=30), 3 immunizations with 5 NF135.C10 infected mosquitoes (n=10) or no immunizations (n=6). Immunizations in cohort A (n=20) will be performed under mefloquine prophylaxis, spaced 4 weeks apart. In cohort B, volunteers will not take mefloquine prophylaxis, instead all volunteers will be treated presumptively on day 7 after each immunization with a curative regimen of artemether/lumefantrine, regardless of parasitaemia or symptoms. Nineteen weeks after the last immunization, all volunteers plus naïve controls will be challenged either by the bites of 5 NF135.C10 (n=36) or 5 NF54 (n=13) infected mosquitoes. After challenge infection, volunteers will be followed up on an out-patient basis once daily for qPCR and safety lab measurements from day 6 until day 21 post challenge. All volunteers will be treated with a curative regimen of atovaquone/proguanil, either at the time of detection of blood stage parasitemia, or 28 days after challenge infection.

Conditions

• Malaria,Falciparum
• Controlled Human Malaria Infection
• Immunization; Infection

Interventions

Type	Name	Description
BIOLOGICAL	CPS-immunization	Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes while taking mefloquine prophylaxis.
BIOLOGICAL	malaria challenge infection, P. falciparum NF135.C10	Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites.
BIOLOGICAL	malaria challenge infection, P. falciparum NF54	Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF54 sporozoites.
BIOLOGICAL	CPS-immunization (A/L)	Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes and receive presumptive treatment with artemether/lumefantrine initiated on day 7 after each immunization.
DRUG	Atovaquone / Proguanil Oral Tablet [Malarone]	All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.

Timeline

• Start date: 2019-04-01
• Primary completion: 2021-02-01
• Completion: 2021-02-01
• First posted: 2019-01-23
• Last updated: 2023-05-26
• Results posted: 2022-05-11

Locations

1 site across 1 country: Netherlands