Malaria,FalciparumPhase 1/2CHMI-TransModNCT04280692
Controlled Human Malaria Infection Transmission Model - Phase A
A Phase 1/2 study testing PfSPZ Challenge, Sulfadoxine-Pyrimethamine and Piperaquine in people with Malaria,Falciparum, run by University of Oxford at 1 site in Kenya.
Trial summary
This is to develop a model to test the efficacy of vaccines and/or drugs designed to block transmission of malaria to mosquitoes and to identify the targets of transmission-blocking immunity to malaria. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria,Falciparum
- What is being tested?
- PfSPZ Challenge, Sulfadoxine-Pyrimethamine and Piperaquine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteKenya
- Study dates
- 22 Aug 2022to Aug 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adults aged 18 to 45 years.
- Able and willing (in the Investigator's opinion) to comply with all study requirements.
- Informed consent.
- Use of effective method of contraception for duration of study (women only). We will ask the female volunteers to come with their family planning records to verify. Effective contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly, in accordance with the product label. Examples of these include: combined oral contraceptives; injectable progestogen; implants of etenogestrel or levonorgestrel; intrauterine device or intrauterine system; male partner sterilisation at least 6 months prior to the female subject's entry into the study, and the relationship is monogamous; male condom combined with a vaginal spermicide (foam, gel, film, cream or suppository); and male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository).
Who cannot join
- Body weight of less than 50kg or body mass index (BMI) less than 18 or greater than 25 kg/m2 at screening.
- Use of systemic antibiotics with known antimalarial activity within 30 days of administration of PfSPZ Challenge (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin).
- Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.
- Current participation in another clinical trial or recent participation within 12 weeks of enrolment.
- Prior receipt of an investigational malaria vaccine.
- Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed). This will also include Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) positivity.
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- Use of immunoglobulins or blood products within 3 months prior to enrolment.
- Any serious medical condition reported or identified during screening that increases the risk of CHMI.
- Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination.
- Women only; pregnancy, or an intention to become pregnant during the duration of the study.
- Sickle cell trait or disease.
- History of drug or alcohol abuse.
- Known hypersensitivity to or contraindications for use of artemether-lumefantrine, chloroquine, piperaquine, primaquine, sulfadoxine-pyrimethamine, or history of severe (allergic) reactions to mosquito bites.
- Confirmed gametocyte positivity at screening and/or a day before challenge
- Confirmed parasite positive by PCR a day before challenge i.e. at C-1. Exclusion Criterion on Day of Challenge
- Acute disease, defined as moderate or severe illness with or without fever (temperature >37.5 degrees Celcius).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Safety and Feasibility of a Malaria Transmission Model in Semi-immune Kenyan Adults Using Plasmodium Falciparum Sporozoites
This is to develop a model to test the efficacy of vaccines and/or drugs designed to block transmission of malaria to mosquitoes and to identify the targets of transmission-blocking immunity to malaria.
Read the detailed description
Malaria is a disease of major public health importance. The only vaccine available is partially effective and targets the pre-erythrocytic stages of the life cycle. Thus, there is a need to identify other potential vaccine targets as well as to develop models to test vaccine efficacy, especially that of transmission-blocking vaccines. Controlled human malaria infection (CHMI) has been shown to be an important tool for the assessment of the efficacy of novel malaria vaccines and drugs. CHMI also allows for the evaluation of immunity to malaria and monitoring of parasite growth rates in vivo. This is particularly useful in individuals from endemic areas with varying levels of exposure and immunity to malaria. Thus, CHMI in individuals with prior exposure to malaria has potential to accelerate malaria vaccine development. In this study, the aim is to use CHMI in semi-immune adults to develop a model to assess transmissibility of malaria infection to mosquitoes, to study immune responses that are directed against sexual stages that might block transmission, and as a platform to test vaccines. To achieve this, the study will be carried out in two phases A (N=45 participants) and B (N=60 participants) over a period of 4-6months. Parasite dose will be varied in individuals enrolled for CHMI and use of low-doses of anti-malarial drugs to promote the production of gametocytes in vivo (Phase A) and demonstrate transmissibility in mosquito feeding assays (Phase B). Thus, the main outcomes of the study will be: (1) optimisation of sporozoite dose for infections success in individuals with moderate-high malaria exposure; (2) use of sub-curative anti-malaria treatment for induction of gametocytes; and (3) infection of mosquitoes in mosquito feeding assays by induced gametocytes. To achieve this, up to 250 semi-immune adults will be recruited from known areas of malaria endemicity in Kenya with varying exposure to malaria undergo screening procedures after informed consent to enrol 105 individuals to conduct CHMI studies with serial quantitative polymerase chain reaction (PCR) to measure asexual parasite growth and induction of transmission stages in vivo. In addition, comprehensively characterize immunity and identify targets in relation to function assessed by various laboratory assays.
- Conditions
- Malaria,Falciparum
- Being tested
- PfSPZ Challenge, Sulfadoxine-Pyrimethamine, Piperaquine, Artemether lumefantrine, Primaquine
- Keywords
- PfSPZ, Kenya, Gametocytes, Transmission, CHMI, Challenge, semi-immune adults
- Medical subject headings
- Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PfSPZ ChallengeBiological
Also called NF54 Plasmodium falciparum malaria challenge
Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites
Sulfadoxine-PyrimethamineDrug
Also called Fansidar
Sub-curative 500mg/25mg single dose regimen
PiperaquineDrug
Also called Piperaquine Phosphate
Sub-curative 480mg single dose regimen
Artemether lumefantrineDrug
Also called Coartem
Three day curative regimen 20mg/120mg
PrimaquineDrug
Single low dose regimen 0.25 mg base/kg
| Study group | Role | What they receive |
|---|---|---|
| Group 1: PfSPZ 6,400 | Experimental | Group 1 will receive a malaria infection by direct venous inoculation (DVI) with PfSPZ Challenge at a dose of 6,400 sporozoites.
Group 1 will be randomised (1:1) to receive either sub-curative Sulfadoxine-Pyrimethamine (SP) (500mg/25mg) or Piperaquine (PIP) (480mg).
Group 1 will receive a final curative treatment of Artemether-Lumefantrine (AL) with single low dose Primaquine (SLDPQ) Receives: Biological: PfSPZ Challenge; Drug: Sulfadoxine-Pyrimethamine; Drug: Piperaquine; Drug: Artemether lumefantrine; Drug: Primaquine |
| Group 1: PfSPZ 12,800 | Experimental | Group 2 will receive a malaria infection by direct venous inoculation (DVI) with PfSPZ Challenge at a dose of 12,800 sporozoites
Group 2 will be randomised (1:1) to receive either sub-curative Sulfadoxine-Pyrimethamine (SP) (500mg/25mg) or Piperaquine (PIP) (480mg).
Group 2 will receive a final curative treatment of Artemether-Lumefantrine (AL) with single low dose Primaquine (SLDPQ) Receives: Biological: PfSPZ Challenge; Drug: Sulfadoxine-Pyrimethamine; Drug: Piperaquine; Drug: Artemether lumefantrine; Drug: Primaquine |
| Group 3: PfSPZ 25,600 | Experimental | Group 3 will receive a malaria infection by direct venous inoculation (DVI) with PfSPZ Challenge at a dose of 25,600 sporozoites
Group 3 will be randomised (1:1) to receive either sub-curative Sulfadoxine-Pyrimethamine (SP) (500mg/25mg) or Piperaquine (PIP) (480mg).
Group 3 will receive a final curative treatment of Artemether-Lumefantrine (AL) with single low dose Primaquine (SLDPQ) Receives: Biological: PfSPZ Challenge; Drug: Sulfadoxine-Pyrimethamine; Drug: Piperaquine; Drug: Artemether lumefantrine; Drug: Primaquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and optimisation of sporozoite dose for infections success in individuals with moderate-high malaria exposure
Magnitude and frequency of adverse events in the study groups
Measured: Up to 42 days post infection with PfSPZ challenge
Prevalence of gametocytes
Prevalence of gametocytes as determined by qRT-PCR
Measured: Up to 42 days post infection with PfSPZ challenge
Secondary outcomes (2)
Use of sub-curative anti-malaria treatment for induction of gametocytes
Density of gametocytes as measured by qRT-PCR
Measured: Up to 42 days post infection with PfSPZ challenge
Peak density and time point of gametocytaemia
Peak density and peak time point of gametocytes by drug-regimen and determine the area under the curve of density over time
Measured: Up to 42 days post infection with PfSPZ challenge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2020
- Study start22 Aug 2022
- Primary completionDec 2025 (estimated)
- Study completionAug 2026 (estimated)
Why it stopped: Study halted prematurely due to US FDA clinical hold on PfSPZ Challenge
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.
- More trials run by University of OxfordThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- KEMRI-Wellcome Trust Collaborative Research Program, Sanaria Inc., Kenya Medical Research Institute
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04280692
- Sponsor's protocol ID
- KEMRI/SERU/CGMR-C/117/3759
- Other IDs
- OxTREC 48-18
- Acronym
- CHMI-TransMod
- Status last verified
- May 2024
- First submitted
- 19 Feb 2020
- Last updated
- 23 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Feasibility of a Malaria Transmission Model in Semi-immune Kenyan Adults Using Plasmodium Falciparum Sporozoites
- ClinicalTrials.gov ID
- NCT04280692
- Acronym / sponsor ID
- CHMI-TransMod / KEMRI/SERU/CGMR-C/117/3759
- Conditions
- Malaria,Falciparum
- Keywords
- PfSPZ, Kenya, Gametocytes, Transmission, CHMI, Challenge, semi-immune adults
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Study halted prematurely due to US FDA clinical hold on PfSPZ Challenge
- Enrolment
- 44 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- KEMRI-Wellcome Trust Collaborative Research Program, Sanaria Inc., Kenya Medical Research Institute
- Study start
- 22 Aug 2022 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Aug 2026 (estimated)
- First posted
- 21 Feb 2020 (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.
This is to develop a model to test the efficacy of vaccines and/or drugs designed to block transmission of malaria to mosquitoes and to identify the targets of transmission-blocking immunity to malaria.
Detailed description
Malaria is a disease of major public health importance. The only vaccine available is partially effective and targets the pre-erythrocytic stages of the life cycle. Thus, there is a need to identify other potential vaccine targets as well as to develop models to test vaccine efficacy, especially that of transmission-blocking vaccines. Controlled human malaria infection (CHMI) has been shown to be an important tool for the assessment of the efficacy of novel malaria vaccines and drugs. CHMI also allows for the evaluation of immunity to malaria and monitoring of parasite growth rates in vivo. This is particularly useful in individuals from endemic areas with varying levels of exposure and immunity to malaria. Thus, CHMI in individuals with prior exposure to malaria has potential to accelerate malaria vaccine development. In this study, the aim is to use CHMI in semi-immune adults to develop a model to assess transmissibility of malaria infection to mosquitoes, to study immune responses that are directed against sexual stages that might block transmission, and as a platform to test vaccines. To achieve this, the study will be carried out in two phases A (N=45 participants) and B (N=60 participants) over a period of 4-6months. Parasite dose will be varied in individuals enrolled for CHMI and use of low-doses of anti-malarial drugs to promote the production of gametocytes in vivo (Phase A) and demonstrate transmissibility in mosquito feeding assays (Phase B). Thus, the main outcomes of the study will be: (1) optimisation of sporozoite dose for infections success in individuals with moderate-high malaria exposure; (2) use of sub-curative anti-malaria treatment for induction of gametocytes; and (3) infection of mosquitoes in mosquito feeding assays by induced gametocytes. To achieve this, up to 250 semi-immune adults will be recruited from known areas of malaria endemicity in Kenya with varying exposure to malaria undergo screening procedures after informed consent to enrol 105 individuals to conduct CHMI studies with serial quantitative polymerase chain reaction (PCR) to measure asexual parasite growth and induction of transmission stages in vivo. In addition, comprehensively characterize immunity and identify targets in relation to function assessed by various laboratory assays.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1: PfSPZ 6,400 | Experimental | Biological: PfSPZ Challenge, Drug: Sulfadoxine-Pyrimethamine, Drug: Piperaquine, Drug: Artemether lumefantrine, Drug: PrimaquineGroup 1 will receive a malaria infection by direct venous inoculation (DVI) with PfSPZ Challenge at a dose of 6,400 sporozoites. Group 1 will be randomised (1:1) to receive either sub-curative Sulfadoxine-Pyrimethamine (SP) (500mg/25mg) or Piperaquine (PIP) (480mg). Group 1 will receive a final curative treatment of Artemether-Lumefantrine (AL) with single low dose Primaquine (SLDPQ) |
| Group 1: PfSPZ 12,800 | Experimental | Biological: PfSPZ Challenge, Drug: Sulfadoxine-Pyrimethamine, Drug: Piperaquine, Drug: Artemether lumefantrine, Drug: PrimaquineGroup 2 will receive a malaria infection by direct venous inoculation (DVI) with PfSPZ Challenge at a dose of 12,800 sporozoites Group 2 will be randomised (1:1) to receive either sub-curative Sulfadoxine-Pyrimethamine (SP) (500mg/25mg) or Piperaquine (PIP) (480mg). Group 2 will receive a final curative treatment of Artemether-Lumefantrine (AL) with single low dose Primaquine (SLDPQ) |
| Group 3: PfSPZ 25,600 | Experimental | Biological: PfSPZ Challenge, Drug: Sulfadoxine-Pyrimethamine, Drug: Piperaquine, Drug: Artemether lumefantrine, Drug: PrimaquineGroup 3 will receive a malaria infection by direct venous inoculation (DVI) with PfSPZ Challenge at a dose of 25,600 sporozoites Group 3 will be randomised (1:1) to receive either sub-curative Sulfadoxine-Pyrimethamine (SP) (500mg/25mg) or Piperaquine (PIP) (480mg). Group 3 will receive a final curative treatment of Artemether-Lumefantrine (AL) with single low dose Primaquine (SLDPQ) |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Healthy adults aged 18 to 45 years.
- Able and willing (in the Investigator's opinion) to comply with all study requirements.
- Informed consent.
- Use of effective method of contraception for duration of study (women only). We will ask the female volunteers to come with their family planning records to verify. Effective contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly, in accordance with the product label. Examples of these include: combined oral contraceptives; injectable progestogen; implants of etenogestrel or levonorgestrel; intrauterine device or intrauterine system; male partner sterilisation at least 6 months prior to the female subject's entry into the study, and the relationship is monogamous; male condom combined with a vaginal spermicide (foam, gel, film, cream or suppository); and male condom combined with a female diaphragm, either with or without a vaginal spermicide (foam, gel, film, cream, or suppository).
Key exclusion criteria (16 listed)
- Body weight of less than 50kg or body mass index (BMI) less than 18 or greater than 25 kg/m2 at screening.
- Use of systemic antibiotics with known antimalarial activity within 30 days of administration of PfSPZ Challenge (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin).
- Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.
- Current participation in another clinical trial or recent participation within 12 weeks of enrolment.
- Prior receipt of an investigational malaria vaccine.
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 |
|---|---|---|
| PfSPZ ChallengeAlso: NF54 Plasmodium falciparum malaria challengeAseptic, purified, cryopreserved Plasmodium falciparum sporozoites | Biological | Group 1: PfSPZ 12,800, Group 1: PfSPZ 6,400, Group 3: PfSPZ 25,600 |
| Sulfadoxine-PyrimethamineAlso: FansidarSub-curative 500mg/25mg single dose regimen | Drug | Group 1: PfSPZ 12,800, Group 1: PfSPZ 6,400, Group 3: PfSPZ 25,600 |
| PiperaquineAlso: Piperaquine PhosphateSub-curative 480mg single dose regimen | Drug | Group 1: PfSPZ 12,800, Group 1: PfSPZ 6,400, Group 3: PfSPZ 25,600 |
| Artemether lumefantrineAlso: CoartemThree day curative regimen 20mg/120mg | Drug | Group 1: PfSPZ 12,800, Group 1: PfSPZ 6,400, Group 3: PfSPZ 25,600 |
| PrimaquineSingle low dose regimen 0.25 mg base/kg | Drug | Group 1: PfSPZ 12,800, Group 1: PfSPZ 6,400, Group 3: PfSPZ 25,600 |
Primary outcome
Safety and optimisation of sporozoite dose for infections success in individuals with moderate-high malaria exposure
Time frame: Up to 42 days post infection with PfSPZ challenge
Magnitude and frequency of adverse events in the study groups
Prevalence of gametocytes
Time frame: Up to 42 days post infection with PfSPZ challenge
Prevalence of gametocytes as determined by qRT-PCR
2 secondary outcomes
Use of sub-curative anti-malaria treatment for induction of gametocytes
Time frame: Up to 42 days post infection with PfSPZ challenge
Peak density and time point of gametocytaemia
Time frame: Up to 42 days post infection with PfSPZ challenge
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2024.
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PfSPZ Challenge, Sulfadoxine-Pyrimethamine and Piperaquine in people with Malaria,Falciparum, run by University of Oxford at 1 site in Kenya.
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 4 inclusion and 16 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: paused, as of the sponsor's last update on 23 May 2024. 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 Kenya. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and optimisation of sporozoite dose for infections success in individuals with moderate-high malaria exposure (time frame: Up to 42 days post infection with PfSPZ challenge). The study lists 2 primary outcomes in all. 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 23 May 2024.