Controlled Human Malaria Infection in Semi-Immune Kenyan Adults. (CHMI-SIKA)

NCT ID: NCT02739763

Last Updated: 2016-05-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-31
• Study Completion Date: 2020-11-30

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.

Conditions

Malaria

Keywords

PfSPZ; Semi-immune adults; Kenya; challenge; CHMI; malaria

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Plasmodium falciparum sprozoite (PfSPZ) challenge

Challenge agent

Group Type: EXPERIMENTAL

Plasmodium falciparum sporozoite (PfSPZ)

Intervention Type: BIOLOGICAL

Plasmodium falciparum sporozoites

Interventions

Plasmodium falciparum sporozoite (PfSPZ)

Plasmodium falciparum sporozoites

Intervention Type: BIOLOGICAL

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

KEMRI-Wellcome Trust Collaborative Research Program

OTHER

Sponsor Role: collaborator

Sanaria Inc.

INDUSTRY

Sponsor Role: collaborator

KEMRI Centre for Clinical Research

UNKNOWN

Sponsor Role: collaborator

Pwani University

UNKNOWN

Sponsor Role: collaborator

University of Cambridge

OTHER

Sponsor Role: collaborator

Wellcome Sanger Institute

OTHER

Sponsor Role: collaborator

University of Oxford

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philip Bejon, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

KEMRI Wellcome Trust Research Programme and University of Oxford

Locations

KEMRI Wellcome Trust Research Programme

Kilifi, Coast, Kenya

Site Status: RECRUITING

KEMRI Centre for Clinical Research

Nairobi, Nairobi County, Kenya

Site Status: NOT_YET_RECRUITING

Countries

Kenya

Central Contacts

Melissa Kapulu, DPhil

Role: CONTACT

Phone: +254709983463

Email: MKapulu@kemri-wellcome.org

Patricia Njuguna, MMed, MSc

Role: CONTACT

Phone: +254709983534

Facility Contacts

Melissa Kapulu, DPhil

Role: primary

Patricia Njuguna, MMed, MSc

Role: backup

Elizabeth Juma, MMed, MPH

Role: primary

References

Kariuki 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.

Reference Type: DERIVED

PMID: 37310872 (View on PubMed)

Li 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.

Reference Type: DERIVED

PMID: 37309249 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35835738 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35073864 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34264864 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31803847 (View on PubMed)

Other Identifiers

KEMRI/CGMRC/CSC/029/2015

Identifier Type: OTHER

Identifier Source: secondary_id

OXTREC 2-16

Identifier Type: -

Identifier Source: org_study_id