Clinical trial NCT02739763: Controlled Human Malaria Infection in Semi-Immune Kenyan Adults. (CHMI-SIKA)
Official title: Controlled Human Malaria Infection (CHMI) to Assess Human Immunity to P. Falciparum Using Sporozoites Administered by Direct Venous Inoculation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Malaria
Keywords: PfSPZ
Semi-immune adults
Kenya
challenge
CHMI
malaria
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: KEMRI-Wellcome Trust Collaborative Research Program
name: Sanaria Inc.
name: KEMRI Centre for Clinical Research
name: Pwani University
name: University of Cambridge
name: Wellcome Sanger Institute
First posted: 2016-04-15
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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.
* 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.

Exclusion Criterion on Day of Challenge:

• Acute disease, defined as moderate or severe illness with or without fever (temperature \>37.5°C).

Primary outcomes:
measure: Infectivity of PfSPZ (malaria infection) as determined by quantitative PCR
timeFrame: day 7 to day 21
Secondary outcomes:
measure: Safety profile of PfSPZ challenge via direct venous injection
timeFrame: day 0 to day 21
measure: Parasite growth rates with respect to antibody responses to over 100 falciparum antigens
timeFrame: day 7 to day 21
Other outcomes:
Locations:
city: Kilifi
country: Kenya
facility: KEMRI Wellcome Trust Research Programme
state: Coast
city: Nairobi
country: Kenya
facility: KEMRI Centre for Clinical Research
Study officials:
affiliation: KEMRI Wellcome Trust Research Programme and University of Oxford
name: Philip Bejon, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Musasia 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.
citation: Kapulu 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.
citation: Kapulu 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.
citation: Kapulu 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.