Malaria FalciparumPhase 1iGP3-SWITCHNCT06881732
Experimental Malaria Infection of Healthy Malaria-Naive Adults by Mosquito Bite With the Genetically Modified Plasmodium Falciparum NF54/iGP3 GAP
A Phase 1 study testing NF54/iGP3 in people with Malaria Falciparum and Malaria Infection, run by University of Melbourne at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria Falciparum, Malaria Infection, Malaria Transmission
- What is being tested?
- NF54/iGP3
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteAustralia
- Study dates
- Jul 2025to Jul 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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)
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- 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
- Ferritin, creatinine and alanine aminotransferase (ALT) within normal laboratory ranges
- No clinically significant abnormality in coagulation or clotting
- Normal G6PD enzyme activity levels as defined by the parameters of the specific quantitative G6PD test performed at screening
- Negative for blood borne viruses, including Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), Human T-lymphotropic virus type 1 (HTLV); and other blood borne pathogens including West Nile Virus (WNV), Babesia species, Treponema pallidum, and Trypanosoma cruzi
- Criteria specific to female participants:
- Post-menopausal for at least 1 one year, post-hysterectomy, or bilateral oophorectomy with a correlating follicle stimulating hormone (FSH) level.
- OR
- Females of childbearing age have a negative beta-human chorionic gonadotrophin (b-HCG) pregnancy test (urine or serum) on day of enrolment and prior to CHMI inoculation and agreement to use effective birth control through the duration of the study.
Who cannot join
- 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
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- 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
- Use of blood products or immunoglobulins within the previous 6 months
- Without good peripheral venous access
- Clinical history of: Sickle cell disease, sickle cell trait or other haemoglobinopathies; Splenectomy or fuctional asplenia; Skeeter syndrome or anaphylactic response to mosquito bites
- Known intolerance, hypersensitivity or other contraindication to artemether or other artemisinin derivatives, lumefantrine, atovaquone, proguanil, primaquine, or artesunate or any of its excipients
- Use or planned use of any drug, including antibiotics, with antimalarial activity four weeks prior to inoculation
- Use of any of the following drugs: Anticoagulants (within 14 days of enrolment); Systemic corticosteroids (within 3 months of enrolment); Any prescription or non-prescription drugs, and or supplements that in the opinion of the investigator would jeopardise the safety of the volunteer
- Any other chronic or clinically significant medical condition that in the opinion of the investigator would jeopardize the safety or rights of the volunteer, including but not limited to: diabetes mellitus type I, chronic hepatitis; OR clinically significant forms of: drug or alcohol abuse, asthma, autoimmune disease, infectious diseases, psychiatric disorders, heart disease, or cancer
- Clinical Risk:
- Evidence at screening of increased cardiovascular disease risk (defined as >10%, 5-year risk for those greater than 35 years of age), as determined by the Australian Absolute Cardiovascular Disease Risk Calculator
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Australia1 site
Doherty Clinical Trials
Melbourne, Victoria, 3002
Tim Crocker-Buque, +61 (03) 9970 4200, tcrockerbuque@dohertyclinicaltrials.com
Tim Crocker-Buque
About this study
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.
Read the 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.
- Conditions
- Malaria Falciparum, Malaria Infection, Malaria Transmission
- Being tested
- NF54/iGP3
- Keywords
- SWITCH, NF54/iGP3, Plasmodium falciparum
- Medical subject headings
- Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NF54/iGP3Biological
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.
| Study group | Role | What they receive |
|---|---|---|
| Plasmodium falciparum NF54/iGP3 | Experimental | Infection by direct feeding of Anopheles stephensi mosquitoes infected with Plasmodium falciparum NF54/iGP3 Receives: Biological: NF54/iGP3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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).
Measure the change in parasite count (parasites/mL) of blood-stage NF54/iGP3 parasites via qPCR, following inoculation until the administration of antimalarial treatment.
Measured: 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).
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.
Measured: 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.
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.
Measured: From Inoculation (Day 1) until parasitemia conditions are met, truncated at Day 22
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2025
- Study startJul 2025 (estimated)
- Primary completionJul 2026 (estimated)
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malaria FalciparumStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All participants enrolled into the study will be infected with the malaria parasite.
- Masking
- None (open label)
- Enrolment
- 2 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Melbourne
- Sponsor type
- University, hospital or other
- Collaborators
- Walter and Eliza Hall Institute of Medical Research, Swiss Tropical & Public Health Institute, QIMR Berghofer Medical Research Institute
- Responsible party
- Sponsor
- Investigators
- James McCarthy, Principal investigator, University of Melbourne
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06881732
- Sponsor's protocol ID
- UoM/DCT/2024-02
- Acronym
- iGP3-SWITCH
- Status last verified
- Feb 2025
- First submitted
- 27 Feb 2025
- Last updated
- 18 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Experimental Malaria Infection of Healthy Malaria-Naive Adults by Mosquito Bite With the Genetically Modified Plasmodium Falciparum NF54/iGP3 GAP
- ClinicalTrials.gov ID
- NCT06881732
- Acronym / sponsor ID
- iGP3-SWITCH / UoM/DCT/2024-02
- Conditions
- Malaria Falciparum, Malaria Infection, Malaria Transmission
- Keywords
- SWITCH, NF54/iGP3, Plasmodium falciparum
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 2 participants (estimated)
- Lead sponsor
- University of MelbourneUniversity, hospital or other
- Collaborators
- Walter and Eliza Hall Institute of Medical Research, Swiss Tropical & Public Health Institute, QIMR Berghofer Medical Research Institute
- Study start
- Jul 2025 (estimated)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Jul 2026 (estimated)
- First posted
- 18 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All participants enrolled into the study will be infected with the malaria parasite.
| Arm | Type | Receives |
|---|---|---|
| Plasmodium falciparum NF54/iGP3 | Experimental | Biological: NF54/iGP3Infection by direct feeding of Anopheles stephensi mosquitoes infected with Plasmodium falciparum NF54/iGP3 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (23 listed)
- 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
Key exclusion criteria (24 listed)
- 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
- Any previous history of malaria infection, including participation in a malaria research study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NF54/iGP3Mosquito-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. | Biological | Plasmodium falciparum NF54/iGP3 |
Primary outcome
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.
Time frame: 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.
3 secondary outcomes
To characterise the parasite growth profile of all blood stage parasites in participants following infection with NF54/iGP3 using qPCR (parasites/mL).
Time frame: 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).
Time frame: 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.
Time frame: From Inoculation (Day 1) until parasitemia conditions are met, truncated at Day 22
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
James McCarthy principal investigator
University of Melbourne
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NF54/iGP3 in people with Malaria Falciparum and Malaria Infection, run by University of Melbourne at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 18 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dana de Kretser (+61 (03) 9342 9401, dana.dekretser@unimelb.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: From Inoculation (Day 1) until End of Study (Day 180)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2025.