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Clinical Trial Summary

Controlled human malaria infection (CHMI) is an important tool for the assessment of the efficacy of novel malaria vaccines and drugs prior to field trials. CHMI also allows for the evaluation of immunity to malaria and parasite growth rates in vivo and thus allows for the assessment of the natural acquisition and loss of malaria immunity. This may be particularly useful in individuals from endemic areas with changing levels of exposure and immunity to malaria. Thus, CHMI in individuals with prior exposure to malaria could be a valuable tool to accelerate malaria vaccine development and inform malaria control programs of changing immunity levels and related disease presentations. In this trial, the investigators intend to study the effect of pre-exposure to Plasmodium falciparum (Pf) on parasite kinetics, clinical symptoms and immunity after CHMI by PfSPZ Challenge in Gambian adults. Based on a well-defined sero-profile representing the extremes of current malaria exposure in The Gambia, two cohorts will be identified to study the impact of naturally acquired immunity on susceptibility for a Controlled Human Malaria Infection.

Clinical Trial Description

The main hypothesis is that cumulative exposure to natural Pf infections, as defined by the antibody profile to a defined panel of Pf antigens, is associated with an increasing pre-patent period and/or a reduced parasite growth rate in the CHMI after PfSPZ Challenge. The Primary objectives are to assess safety of PfSPZ Challenge administration in Gambian adults and to determine parasite kinetics in the CHMI model after PfSPZ Challenge in naturally exposed Gambian adults. The Secondary objective is to analyse humoral and cellular immune responses before and after CHMI in Gambian adults with different serological profiles to a panel of defined Pf-antigens.

The study is a single centre open-label clinical trial. The study population will be adult (aged 18 to 35 years) male, healthy subjects with at least 4 years of secondary school education. A total of 30 individuals will be enrolled to participate in the study; 15 with intense previous and recent exposure to malaria infections and 15 with very limited historic exposure to malaria and no evidence of recent malaria infections.

All participants will be checked for parasitaemia by qPCR before inclusion. Two subsequent negative qPCRs are needed before enrolment in the study to assure the absence of a P.falciparum infection. If one of the participants is not fit to participate in the study, another participant who fulfilled enrolment criteria will be included as replacement. For this purpose, two to four additional participants will be screened as back up. Subsequently, all participants will be subjected to a standard controlled human malaria infection (CHMI) by IV administration of a dose of 3.2 x 10^3 PfSPZ Challenge. After CHMI, participants will be closely followed with regular visits to the clinical trial centre (twice daily until day 15, and daily until day 28 or treatment) consisting of periodic physical examinations, frequent blood sampling and recording of adverse events in their diary. All relevant investigations will be carried out on an outpatient basis, including frequent safety analyses.

Participants should have access to a mobile phone upon which they can be reached 24 hours per day and 7 days per week. As additional safety precaution, participants are required to stay in a hotel/hostel close to the study facility from day 5 post-infection until 3 days after treatment. This mandatory stay in a hotel/hostel is to ensure study participants can be observed at all times and have excellent access to the clinical team. All participants will be treated with a curative regimen of artemether-lumefantrine that radically clears asexual parasites and developing gametocytes. The criteria for treatment post-CHMI will include positive thick smear during follow-up, decision of the study clinician or the local safety monitor, on request of the participant or on day 28 post-CHMI. All participants will be checked for parasites by thick smear at least twice after treatment. ;

Study Design

Related Conditions & MeSH terms

NCT number NCT03496454
Study type Interventional
Source London School of Hygiene and Tropical Medicine
Status Completed
Phase N/A
Start date March 29, 2018
Completion date December 5, 2018

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