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

NCT06881732 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: UoM/DCT/2024-02
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Malaria Falciparum; Malaria Infection; Malaria Transmission

Keywords

SWITCH; NF54/iGP3; Plasmodium falciparum

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  From Inoculation (Day 1) until End of Study (Day 180)

Secondary Outcomes (3)

• 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)

• 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 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

Study Arms (1)

Plasmodium falciparum NF54/iGP3

EXPERIMENTAL

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

Biological: NF54/iGP3

Interventions

NF54/iGP3 BIOLOGICAL

Mosquito-generated sporozoites of the genetically modified, inducible gametocyte-producing parasite line NF54/iGP3, created via CRISPR/Cas9 genetic engineering of the parental wildtype strain Plasmodium falciparum (Pf) NF54 to contain a trimethoprim (TMP)-inducible copy of the Pf gdv1 gene in the dispensable Pf cg6 locus.

Plasmodium falciparum NF54/iGP3

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able and willing to complete the informed consent process
• Available for the entire planned study duration
• Male or Female
• Aged 18 to 55 years
• Willing to have blood samples collected, stored indefinitely and used for research purposes
• Willing to defer blood donations for at least six months after the EoS visit (D180)
• Agreement to adhere to specific Lifestyle Considerations throughout study duration
• Clinical Criteria:
• Total body weight ≥ 50 kg, and a body mass index (BMI) within the range of 18 to 32 kg/m2 (inclusive)
• In good general physical and mental health as evaluated through a comprehensive clinical assessment
• Vital signs at screening and pre-inoculation within normal clinical range
• Electrocardiograph (ECG) without significant abnormalities, including: QTcF ≤450 ms for males, QTcF ≤470 ms for females, PR interval ≤210 ms
• Laboratory Criteria:
• O negative blood type
• Haemoglobin, white cell count and platelet levels within normal laboratory ranges

You may not qualify if:

• Participant lives alone and is unable provide contact details of a support person who is aware of the individual's participation in the study and is available to provide assistance if required
• Participation in any investigational product study within the 12 weeks preceding inoculation
• Positive urine drug test at screening or on the day of malaria inoculation unless there is an explanation acceptable to the Investigator (e.g. the volunteer has stated in advance that they consumed a prescription or over-the-counter product which contained the detected drug) and/or the volunteer has a negative urine drug screen on retest by the pathology laboratory
• Positive alcohol breath test at screening or on the day of malaria inoculation
• Malaria History:
• Any previous history of malaria infection, including participation in a malaria research study
• Receipt of a malaria vaccination at any time, including as part of a research study
• Travelled to or lived (more than two weeks) in a malaria-endemic region during the past 12 months or planned travel to a malaria-endemic region over the course of the study
• Lived for more than one year in a malaria-endemic region in the past 10 years
• Lived in a malaria-endemic region for more than 10 years inclusive
• Clinical History:
• Anyone who is pregnant, breastfeeding or planning pregnancy during the study period
• History of severe allergic reaction, including angioedema or anaphylaxis
• Receipt of any live attenuated vaccines within 21 days prior to enrolment
• Has ever received a blood transfusion

Sponsors & Collaborators

• University of Melbourne: lead
• Walter and Eliza Hall Institute of Medical Research: collaborator
• Swiss Tropical & Public Health Institute: collaborator
• QIMR Berghofer Medical Research Institute: collaborator

Study Sites (1)

Doherty Clinical Trials

Melbourne, Victoria, 3002, Australia

Location

MeSH Terms

Conditions

Malaria, Falciparum

Condition Hierarchy (Ancestors)

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

Study Officials

• James McCarthy

  University of Melbourne

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dana de Kretser

CONTACT

+61 (03) 9342 9401; dana.dekretser@unimelb.edu.au

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All participants enrolled into the study will be infected with the malaria parasite.

Study Record Dates

• First Submitted: February 27, 2025
• First Posted: March 18, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: March 18, 2025

Record last verified: 2025-02

Locations

AU (1)