MalariaPhase 1CHMI-SIKANCT02739763
Controlled Human Malaria Infection in Semi-Immune Kenyan Adults. (CHMI-SIKA)
A Phase 1 study testing Plasmodium falciparum sporozoite (PfSPZ) in people with Malaria, run by University of Oxford at 2 sites in Kenya.
Trial summary
The investigators wish to understand how resistance to malaria develops and how this affects the growth rate of malaria in individuals who have past exposure 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
- What is being tested?
- Plasmodium falciparum sporozoite (PfSPZ)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 2 sitesKenya
- Study dates
- May 2016to Nov 2020
- Phase
- Phase 1
- 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). The investigators 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
- 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).
- Use of immunoglobulins or blood products within 3 months prior to enrolment.
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- 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.
- Confirmed parasite positive by PCR a day before challenge i.e. at C-1.
- Acute disease, defined as moderate or severe illness with or without fever (temperature >37.5°C).
Trial locations and contacts
2 sites in 1 country.
Patricia Njuguna, MMed, MSc contact
Kenya2 sites, 2 recruiting
- Recruiting
KEMRI Wellcome Trust Research Programme
Kilifi, Coast, 80108
Melissa Kapulu, DPhil, +254709983463, MKapulu@kemri-wellcome.org
Patricia Njuguna, MMed, MSc, +254709983534, PNjuguna@kemri-wellcome.org
- Not yet recruiting
KEMRI Centre for Clinical Research
Nairobi, Nairobi County
Elizabeth Juma, MMed, MPH, jumaelizabeth@yahoo.com
Bernhards Ogutu, MBChB, PhD
About this study
Official title: Controlled Human Malaria Infection (CHMI) to Assess Human Immunity to P. Falciparum Using Sporozoites Administered by Direct Venous Inoculation
The investigators wish to understand how resistance to malaria develops and how this affects the growth rate of malaria in individuals who have past exposure to malaria.
Read the detailed description
Malaria remains a major public health threat despite regulatory approval of a partially effective pre-erythrocytic malaria vaccine. There is an urgent need to accelerate the development of a more effective multi-stage vaccine. 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 prior to field trials. CHMI also allows for the evaluation of immunity to malaria and parasite growth rates in vivo. This is particularly useful in individuals from endemic areas with a level 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. In this study, the investigators aim to use CHMI in semi-immune adults to provide a comprehensive prioritization of antigens associated with blood-stage immunity for vaccine development. The investigators will comprehensively characterize immunity to malaria using >100 antigens in up to 2,000 semi-immune adults, from known areas of malaria endemicity in Kenya, then select 200 individuals with a range of different immunological profiles, and conduct CHMI studies with serial quantitative polymerase chain reaction (PCR) to measure the parasite growth rate in vivo and relate this to host immunity. This will also involve analysing the relationship with functional immunity assessed by laboratory assays.
- Conditions
- Malaria
- Being tested
- Plasmodium falciparum sporozoite (PfSPZ)
- Keywords
- PfSPZ, Semi-immune adults, Kenya, challenge, CHMI, malaria
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plasmodium falciparum sporozoite (PfSPZ)Biological
Plasmodium falciparum sporozoites
| Study group | Role | What they receive |
|---|---|---|
| Plasmodium falciparum sprozoite (PfSPZ) challenge | Experimental | Challenge agent Receives: Biological: Plasmodium falciparum sporozoite (PfSPZ) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Infectivity of PfSPZ (malaria infection) as determined by quantitative PCR
Measured: day 7 to day 21
Secondary outcomes (2)
Safety profile of PfSPZ challenge via direct venous injection
Measured: day 0 to day 21
Parasite growth rates with respect to antibody responses to over 100 falciparum antigens
Measured: day 7 to day 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2016 (estimated)
- Study startMay 2016
- Primary completionJan 2020 (estimated)
- Study completionNov 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies 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
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- KEMRI-Wellcome Trust Collaborative Research Program, Sanaria Inc., KEMRI Centre for Clinical Research, Pwani University, University of Cambridge, Wellcome Sanger Institute
- Responsible party
- Sponsor
- Investigators
- Philip Bejon, MD,PhD, Principal investigator, KEMRI Wellcome Trust Research Programme and University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02739763
- Sponsor's protocol ID
- OXTREC 2-16
- Other IDs
- KEMRI/CGMRC/CSC/029/2015
- Acronym
- CHMI-SIKA
- Status last verified
- May 2016
- First submitted
- 13 Apr 2016
- Last updated
- 30 May 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Study information will be made available through an open repository. The information to be made available will be anonymized so that there is no link to participants and will include data on antibody responses, parasite growth rates and any other data generated from samples obtained in this study, both generated from this current protocol or any future studies which will require additional ethical approval.
Publications
Ogwang R, Nkumama IN, Mwai K, Odera D, Nyamako L, Furle K, Rosenkranz M, Kimathi R, Njuguna P, Sim BKL, Hamaluba M, Frank R; CHMI-SIKA Study Team; Kapulu MC, Bejon P, Tuju J, Osier FHA. Controlled human malaria infection in adults identify combinations of merozoite antigens associated with clinical immunity. Nat Commun. 2026 May 5;17(1):6472. doi: 10.1038/s41467-026-72716-x.
PubMed 42086568Kariuki SN, Macharia AW, Makale J, Nyamu W, Hoffman SL, Kapulu MC, Bejon P, Rayner JC, Williams TN; CHMI-SIKA Study Team. The Dantu blood group prevents parasite growth in vivo: Evidence from a controlled human malaria infection study. Elife. 2023 Jun 13;12:e83874. doi: 10.7554/eLife.83874.
PubMed 37310872Li K, Tsukasa Y, Kurio M, Maeta K, Tsumadori A, Baba S, Nishimura R, Murakami A, Onodera K, Morimoto T, Uemura T, Usui T. Belly roll, a GPI-anchored Ly6 protein, regulates Drosophila melanogaster escape behaviors by modulating the excitability of nociceptive peptidergic interneurons. Elife. 2023 Jun 13;12:e83856. doi: 10.7554/eLife.83856.
PubMed 37309249Musasia FK, Nkumama IN, Frank R, Kipkemboi V, Schneider M, Mwai K, Odera DO, Rosenkranz M, Furle K, Kimani D, Tuju J, Njuguna P, Hamaluba M, Kapulu MC, Wardemann H; CHMI-SIKA Study Team; Osier FHA. Phagocytosis of Plasmodium falciparum ring-stage parasites predicts protection against malaria. Nat Commun. 2022 Jul 14;13(1):4098. doi: 10.1038/s41467-022-31640-6.
PubMed 35835738Kapulu MC, Kimani D, Njuguna P, Hamaluba M, Otieno E, Kimathi R, Tuju J, Sim BKL; CHMI-SIKA Study Team. Controlled human malaria infection (CHMI) outcomes in Kenyan adults is associated with prior history of malaria exposure and anti-schizont antibody response. BMC Infect Dis. 2022 Jan 24;22(1):86. doi: 10.1186/s12879-022-07044-8.
PubMed 35073864Kapulu MC, Njuguna P, Hamaluba M, Kimani D, Ngoi JM, Musembi J, Ngoto O, Otieno E, Billingsley PF; Controlled Human Malaria Infection in Semi-Immune Kenyan Adults (CHMI-SIKA) Study Team. Safety and PCR monitoring in 161 semi-immune Kenyan adults following controlled human malaria infection. JCI Insight. 2021 Sep 8;6(17):e146443. doi: 10.1172/jci.insight.146443.
PubMed 34264864Kapulu MC, Njuguna P, Hamaluba MM; CHMI-SIKA Study Team. Controlled Human Malaria Infection in Semi-Immune Kenyan Adults (CHMI-SIKA): a study protocol to investigate in vivo Plasmodium falciparum malaria parasite growth in the context of pre-existing immunity. Wellcome Open Res. 2019 Nov 14;3:155. doi: 10.12688/wellcomeopenres.14909.2. eCollection 2018.
PubMed 31803847
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Controlled Human Malaria Infection (CHMI) to Assess Human Immunity to P. Falciparum Using Sporozoites Administered by Direct Venous Inoculation
- ClinicalTrials.gov ID
- NCT02739763
- Acronym / sponsor ID
- CHMI-SIKA / OXTREC 2-16
- Conditions
- Malaria
- Keywords
- PfSPZ, Semi-immune adults, Kenya, challenge, CHMI, malaria
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- KEMRI-Wellcome Trust Collaborative Research Program, Sanaria Inc., KEMRI Centre for Clinical Research, Pwani University, University of Cambridge, Wellcome Sanger Institute
- Study start
- May 2016
- Primary completion
- Jan 2020 (estimated)
- Study completion
- Nov 2020 (estimated)
- First posted
- 15 Apr 2016 (estimated)
- 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 investigators wish to understand how resistance to malaria develops and how this affects the growth rate of malaria in individuals who have past exposure to malaria.
Detailed description
Malaria remains a major public health threat despite regulatory approval of a partially effective pre-erythrocytic malaria vaccine. There is an urgent need to accelerate the development of a more effective multi-stage vaccine. 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 prior to field trials. CHMI also allows for the evaluation of immunity to malaria and parasite growth rates in vivo. This is particularly useful in individuals from endemic areas with a level 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. In this study, the investigators aim to use CHMI in semi-immune adults to provide a comprehensive prioritization of antigens associated with blood-stage immunity for vaccine development. The investigators will comprehensively characterize immunity to malaria using >100 antigens in up to 2,000 semi-immune adults, from known areas of malaria endemicity in Kenya, then select 200 individuals with a range of different immunological profiles, and conduct CHMI studies with serial quantitative polymerase chain reaction (PCR) to measure the parasite growth rate in vivo and relate this to host immunity. This will also involve analysing the relationship with functional immunity assessed by laboratory assays.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Plasmodium falciparum sprozoite (PfSPZ) challenge | Experimental | Biological: Plasmodium falciparum sporozoite (PfSPZ)Challenge agent |
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). The investigators 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 (11 listed)
- 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).
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 |
|---|---|---|
| Plasmodium falciparum sporozoite (PfSPZ)Plasmodium falciparum sporozoites | Biological | Plasmodium falciparum sprozoite (PfSPZ) challenge |
Primary outcome
Infectivity of PfSPZ (malaria infection) as determined by quantitative PCR
Time frame: day 7 to day 21
2 secondary outcomes
Safety profile of PfSPZ challenge via direct venous injection
Time frame: day 0 to day 21
Parasite growth rates with respect to antibody responses to over 100 falciparum antigens
Time frame: day 7 to day 21
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2016.
- Derived from this study: PubMed 42086568Ogwang R, Nkumama IN, Mwai K, Odera D, Nyamako L, Furle K, Rosenkranz M, Kimathi R, Njuguna P, Sim BKL, Hamaluba M, Frank R; CHMI-SIKA Study Team; Kapulu MC, Bejon P, Tuju J, Osier FHA. Controlled human malaria infection in adults identify combinations of merozoite antigens associated with clinical immunity. Nat Commun. 2026 May 5;17(1):6472. doi: 10.1038/s41467-026-72716-x.
- Derived from this study: PubMed 37310872Kariuki SN, Macharia AW, Makale J, Nyamu W, Hoffman SL, Kapulu MC, Bejon P, Rayner JC, Williams TN; CHMI-SIKA Study Team. The Dantu blood group prevents parasite growth in vivo: Evidence from a controlled human malaria infection study. Elife. 2023 Jun 13;12:e83874. doi: 10.7554/eLife.83874.
- Derived from this study: PubMed 37309249Li K, Tsukasa Y, Kurio M, Maeta K, Tsumadori A, Baba S, Nishimura R, Murakami A, Onodera K, Morimoto T, Uemura T, Usui T. Belly roll, a GPI-anchored Ly6 protein, regulates Drosophila melanogaster escape behaviors by modulating the excitability of nociceptive peptidergic interneurons. Elife. 2023 Jun 13;12:e83856. doi: 10.7554/eLife.83856.
- Derived from this study: PubMed 35835738Musasia FK, Nkumama IN, Frank R, Kipkemboi V, Schneider M, Mwai K, Odera DO, Rosenkranz M, Furle K, Kimani D, Tuju J, Njuguna P, Hamaluba M, Kapulu MC, Wardemann H; CHMI-SIKA Study Team; Osier FHA. Phagocytosis of Plasmodium falciparum ring-stage parasites predicts protection against malaria. Nat Commun. 2022 Jul 14;13(1):4098. doi: 10.1038/s41467-022-31640-6.
- Derived from this study: PubMed 35073864Kapulu MC, Kimani D, Njuguna P, Hamaluba M, Otieno E, Kimathi R, Tuju J, Sim BKL; CHMI-SIKA Study Team. Controlled human malaria infection (CHMI) outcomes in Kenyan adults is associated with prior history of malaria exposure and anti-schizont antibody response. BMC Infect Dis. 2022 Jan 24;22(1):86. doi: 10.1186/s12879-022-07044-8.
- Derived from this study: PubMed 34264864Kapulu MC, Njuguna P, Hamaluba M, Kimani D, Ngoi JM, Musembi J, Ngoto O, Otieno E, Billingsley PF; Controlled Human Malaria Infection in Semi-Immune Kenyan Adults (CHMI-SIKA) Study Team. Safety and PCR monitoring in 161 semi-immune Kenyan adults following controlled human malaria infection. JCI Insight. 2021 Sep 8;6(17):e146443. doi: 10.1172/jci.insight.146443.
- Derived from this study: PubMed 31803847Kapulu MC, Njuguna P, Hamaluba MM; CHMI-SIKA Study Team. Controlled Human Malaria Infection in Semi-Immune Kenyan Adults (CHMI-SIKA): a study protocol to investigate in vivo Plasmodium falciparum malaria parasite growth in the context of pre-existing immunity. Wellcome Open Res. 2019 Nov 14;3:155. doi: 10.12688/wellcomeopenres.14909.2. eCollection 2018.
- Individual participant dataSharing planned: Yes. Study information will be made available through an open repository. The information to be made available will be anonymized so that there is no link to participants and will include data on antibody responses, parasite growth rates and any other data generated from samples obtained in this study, both generated from this current protocol or any future studies which will require additional ethical approval.
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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.
Patricia Njuguna, MMed, MSc contact
Philip Bejon, MD,PhD principal investigator
KEMRI Wellcome Trust Research Programme and University of Oxford
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Plasmodium falciparum sporozoite (PfSPZ) in people with Malaria, run by University of Oxford at 2 sites 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 11 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: status not confirmed, as of the sponsor's last update on 30 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Melissa Kapulu, DPhil (+254709983463, MKapulu@kemri-wellcome.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Infectivity of PfSPZ (malaria infection) as determined by quantitative PCR (time frame: day 7 to day 21). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02739763, which also lists 7 linked publications.
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 30 May 2016.