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

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.

Study Overview

• Status: Unknown
• Conditions: Malaria
• Intervention / Treatment: Biological: Plasmodium falciparum sporozoite (PfSPZ)

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 Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 1

Contacts and Locations

Study Locations

• Kenya
  • Nairobi, Kenya
    • Not yet recruiting
    • KEMRI Centre for Clinical Research
    • Contact: Elizabeth Juma, MMed, MPH; Email: jumaelizabeth@yahoo.com
    • Principal Investigator: Bernhards Ogutu, MBChB, PhD
  • Coast
    • Kilifi, Coast, Kenya, 80108
      • Recruiting
      • KEMRI Wellcome Trust Research Programme
      • Contact: Melissa Kapulu, DPhil; Phone Number: +254709983463; Email: MKapulu@kemri-wellcome.org
      • Contact: Patricia Njuguna, MMed, MSc; Phone Number: +254709983534; Email: PNjuguna@kemri-wellcome.org
      • Principal Investigator: Philip Bejon, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Plasmodium falciparum sprozoite (PfSPZ) challenge; Challenge agent	Biological: Plasmodium falciparum sporozoite (PfSPZ); Plasmodium falciparum sporozoites

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Infectivity of PfSPZ (malaria infection) as determined by quantitative PCR	day 7 to day 21

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety profile of PfSPZ challenge via direct venous injection	day 0 to day 21
Parasite growth rates with respect to antibody responses to over 100 falciparum antigens	day 7 to day 21

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: Sanaria Inc.; KEMRI-Wellcome Trust Collaborative Research Program; University of Cambridge; KEMRI Centre for Clinical Research; Pwani University; Wellcome Trust Sanger Institute
• Investigators: Principal Investigator: Philip Bejon, MD,PhD, KEMRI Wellcome Trust Research Programme and University of Oxford

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2016
• Primary Completion (Anticipated): January 1, 2020
• Study Completion (Anticipated): November 1, 2020

Study Registration Dates

• First Submitted: April 13, 2016
• First Submitted That Met QC Criteria: April 13, 2016
• First Posted (Estimate): April 15, 2016

Study Record Updates

• Last Update Posted (Estimate): May 30, 2016
• Last Update Submitted That Met QC Criteria: May 27, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Kenya; malaria; challenge; PfSPZ; Semi-immune adults; CHMI
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria
• Other Study ID Numbers: OXTREC 2-16; KEMRI/CGMRC/CSC/029/2015 (Other Identifier: KEMRI Scientific and Ethics Review Unit)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: 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.