Experimental Malaria Infection of Healthy Malaria-Naive Adults by Mosquito Bite with the Genetically Modified Plasmodium Falciparum NF54/iGP3 GAP

Phase 1

Not yet recruiting

• Conditions: Malaria Falciparum; Malaria Infection; Malaria Transmission
• Interventions: Biological: NF54/iGP3

• Registration Number: NCT06881732
• Lead Sponsor: University of Melbourne

Brief Summary

The goal of this clinical trial is to learn if the genetically-modified malaria parasite NF54/iGP3 will safely infect humans with malaria. The investigators will also determine how the parasite grows in humans, and the effect of anti-malarial drugs.

Researchers will use a controlled human malaria infection (CHMI) model to infect participants with malaria to observe the development of the disease, collect malaria-infected blood, and then treat the participants to cure the malaria infection.

The collected malaria-infected blood will be used to create a frozen stock of malaria parasites for use in future research.

Detailed Description

Malaria is caused by the Plasmodium parasite and is spread through the bite of mosquitos. During the blood stage of a malaria infection, the parasite can be found in four different forms. Most antimalarial drugs effectively kill the parasites, however, they do not kill one form of the parasite known as gametocytes. Gametocytes are important in the spread of malaria as they are the only form which can be passed from human back to a mosquito.

Currently, primaquine (an antimalarial drug) is the only medicine which kills gametocytes. However, this cannot be given to everyone. Individuals with certain genetic and metabolic disorders, including glucose-6-phosphate dehydrogenase (G6PD) deficiency, face severe health risks if they take Primaquine. Testing for G6PD deficiency is expensive and not available worldwide, which further reduces the number of individuals who can safely take this medication. Therefore, researchers need to develop new antimalarial drugs which kill gametocytes that are safe for all people.

Developing an improved controlled human malaria infection (CHMI) model which produces more gametocytes is a crucial step in advancing antimalarial research, especially targeting the transmission stage. To achieve this, the investigators have created a laboratory made genetically modified (change in DNA), malaria parasite known as Plasmodium falciparum NF54/iGP3, which makes an increased number of gametocytes in comparison with naturally occurring malaria parasites.

The purpose of this study is to develop a CHMI with NF54/iGP3 genetically altered parasites to assess the safety of infecting humans with this malaria parasite as well as determine the growth of the malaria parasites in humans and the effect of anti-malarial drugs. Samples from this study will be used to create a master cell bank of the NF54/iGP3 parasite, so that future research can be carried out using a malaria blood-stage infection model that will produce a greater proportion of gametocytes during infection.

The importance of this research is crucial for the future development and testing of new treatments and vaccines against malarial gametocytes. The development of new antimalarial drugs against malarial gametocytes will over time prevent malaria being transmitted from humans to mosquitos ultimately eliminating the continual spread of malaria.

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-27
• Study First Submitted QC: 2025-03-11
• Last Update Submitted: 2025-03-11
• Study First Posted: 2025-03-18
• Last Update Posted: 2025-03-18
• Study Start: 2025-07
• Primary Completion: 2026-07
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Plasmodium falciparum NF54/iGP3	NF54/iGP3	Infection by direct feeding of Anopheles stephensi mosquitoes infected with Plasmodium falciparum NF54/iGP3

Primary Outcome Measures

Name	Time	Method
To assess the infectivity, safety and tolerability of mosquito bite sporozoite challenge with NF54/iGP3 in healthy malaria-naïve participants by counting solicited and unsolicited adverse events.	From Inoculation (Day 1) until End of Study (Day 180)	Count the occurrence and assess the severity of local and systemic, solicited and unsolicited adverse events using CTCAE v5.0, following administration of NF54/iGP3 by mosquito bite.

Secondary Outcome Measures

Name	Time	Method
To characterise the parasite growth profile of all blood stage parasites in participants following infection with NF54/iGP3 using qPCR (parasites/mL).	From Inoculation (Day 1) until conditions for treatment are met (truncated at Day 22)	Measure the change in parasite count (parasites/mL) of blood-stage NF54/iGP3 parasites via qPCR, following inoculation until the administration of antimalarial treatment.
To characterise the post-treatment clearance profile of all blood stage parasites in participants following infection with NF54/iGP3 using qPCR (parasites/mL).	From administration of antimalarial treatment until End of Study (Day 180)	Measure the change in parasite count (parasites/mL) of blood-stage NF54/iGP3 parasites via qPCR, following administration of registered schizonticidal and gametocidal antimalarial treatments.
Measure the parasite count (parasites/mL) using qPCR in the participant's blood at the time of large volume blood withdrawal.	From Inoculation (Day 1) until parasitemia conditions are met, truncated at Day 22	Measure the parasite count (parasites/mL) via qPCR in collected blood samples from study participants infected with NF54/iGP3, to determine the level of parasitemia.

Trial Locations

Locations (1)

Doherty Clinical Trials; 🇦🇺 Melbourne, Victoria, Australia