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Clinical Trial Details — Status: Suspended

Administrative data

NCT number NCT04280692
Other study ID # KEMRI/SERU/CGMR-C/117/3759
Secondary ID OxTREC 48-18
Status Suspended
Phase Phase 1/Phase 2
First received
Last updated
Start date August 22, 2022
Est. completion date August 2026

Study information

Verified date May 2024
Source University of Oxford
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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.


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.


Recruitment information / eligibility

Status Suspended
Enrollment 44
Est. completion date August 2026
Est. primary completion date December 2025
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 45 Years
Eligibility Inclusion Criteria: 1. Healthy adults aged 18 to 45 years. 2. Able and willing (in the Investigator's opinion) to comply with all study requirements. 3. Informed consent. 4. 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). Exclusion Criteria: 1. Body weight of less than 50kg or body mass index (BMI) less than 18 or greater than 25 kg/m2 at screening. 2. 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). 3. Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period. 4. Current participation in another clinical trial or recent participation within 12 weeks of enrolment. 5. Prior receipt of an investigational malaria vaccine. 6. 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. 7. Use of immunoglobulins or blood products within 3 months prior to enrolment. 8. Any serious medical condition reported or identified during screening that increases the risk of CHMI. 9. Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination. 10. Women only; pregnancy, or an intention to become pregnant during the duration of the study. 11. Sickle cell trait or disease. 12. History of drug or alcohol abuse. 13. Known hypersensitivity to or contraindications for use of artemether-lumefantrine, chloroquine, piperaquine, primaquine, sulfadoxine-pyrimethamine, or history of severe (allergic) reactions to mosquito bites. 14. Confirmed gametocyte positivity at screening and/or a day before challenge 15. 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).

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
PfSPZ Challenge
Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites
Drug:
Sulfadoxine-Pyrimethamine
Sub-curative 500mg/25mg single dose regimen
Piperaquine
Sub-curative 480mg single dose regimen
Artemether lumefantrine
Three day curative regimen 20mg/120mg
Primaquine
Single low dose regimen 0.25 mg base/kg

Locations

Country Name City State
Kenya KEMRI-Wellcome Trust Research Programme Kilifi

Sponsors (4)

Lead Sponsor Collaborator
University of Oxford KEMRI-Wellcome Trust Collaborative Research Program, Kenya Medical Research Institute, Sanaria Inc.

Country where clinical trial is conducted

Kenya, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Up to 42 days post infection with PfSPZ challenge
Primary Prevalence of gametocytes Prevalence of gametocytes as determined by qRT-PCR Up to 42 days post infection with PfSPZ challenge
Secondary Use of sub-curative anti-malaria treatment for induction of gametocytes Density of gametocytes as measured by qRT-PCR Up to 42 days post infection with PfSPZ challenge
Secondary 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 Up to 42 days post infection with PfSPZ challenge
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