Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202108851511956 Date of Approval: 24/08/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Controlled Human Malaria Infection Transmission Model - Phase A (CHMI-TransMod)
Official scientific title Safety and feasibility of a malaria transmission model in semi-immune Kenyan adults using Plasmodium falciparum sporozoites
Brief summary describing the background and objectives of the trial Malaria remains a major public health problem with up to half a billion-people infected with the parasite that causes the disease. In recent and ongoing studies, we have conducted controlled malaria infection in 189 Kenyan adults. By measuring malaria parasites in the blood, we have gained insights into the growth of parasites that will guide vaccine development. One other approach to vaccination is to target the transmitting stages of the malaria parasites such that mosquitoes feeding on the infected person would not become infected, thus breaking the life cycle of the parasite. There is a need to develop experimental methods to test the effect of candidate vaccines designed to interrupt transmission to mosquitoes so that vaccines showing evidence of efficacy can then be prioritized for large trials in the field. Furthermore, studying natural immunity in humans to the stages involved in malaria transmission will help characterize potential targets for new vaccines.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) CHMI TransMod
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Treatment: Other
Anticipated trial start date 01/09/2021
Actual trial start date
Anticipated date of last follow up 01/09/2022
Actual Last follow-up date
Anticipated target sample size (number of participants) 44
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
NCT04280692 Clinicaltrials.gov
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group PfSPZ Challenge 6,400 46 days Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (NF54 Plasmodium falciparum malaria challenge) 12
Control Group None None None None 0 Uncontrolled
Experimental Group PfSPZ Challenge 12,800 46 days Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (NF54 Plasmodium falciparum malaria challenge) 12
Experimental Group PfSPZ Challenge 25,600 46 days Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites (NF54 Plasmodium falciparum malaria challenge) 20
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• 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). 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). • Body weight of less than 50kg or body mass index (BMI) less than 18 or greater than 25 kg/m2 at screening. • 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). This will also include Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) positivity. • 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. • Sickle cell trait or disease. • History of drug or alcohol abuse. • Known hypersensitivity to or contraindications for use of artemether-lumefantrine, chloroquine, piperaquine, primaquine, sulfadoxine-pyrimethamine, or history of severe (allergic) reactions to mosquito bites. • Confirmed gametocyte positivity at screening and/or a day before challenge • Confirmed parasite positive by PCR a day before challenge i.e. at C-1. Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 45 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 18/03/2019 Scientific Ethics Research Unit
Ethics Committee Address
Street address City Postal code Country
OFF MBAGATHI ROAD Nairobi 00200 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 29/03/2019 OxTREC
Ethics Committee Address
Street address City Postal code Country
Wellington Square Oxford OX1 2JD United Kingdom
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Safety and optimisation of sporozoite dose for infections success in individuals with moderate-high malaria exposure [ Time Frame: Up to 42 days post infection with PfSPZ challenge ] Magnitude and frequency of adverse events in the study groups Prevalence of gametocytes [ Time Frame: Up to 42 days post infection with PfSPZ challenge ] Prevalence of gametocytes as determined by qRT-PCR 42 days
Secondary Outcome Use of sub-curative anti-malaria treatment for induction of gametocytes [ Time Frame: Up to 42 days post infection with PfSPZ challenge ] Density of gametocytes as measured by qRT-PCR Peak density and time point of gametocytaemia [ Time Frame: Up to 42 days post infection with PfSPZ challenge ] Peak density and peak time point of gametocytes by drug-regimen and determine the area under the curve of density over time 42 days
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
KEMRI Wellcome Trust Research Programme Centre for Geographic Medical Research Coast Kilifi County Hospital Road Kilifi 80108 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Wellcome Trust Gibbs Building 215 Euston Road, London NW1 2BE United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Oxford Wellington Square Oxford OX1 2JD United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Sanaria Inc 9800 Medical Center Drive A209 Rockville MD 20850 United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Melissa Kapulu MKapulu@kemri-wellcome.org +254709983463 Centre for Geographic Medical Research Coast Kilifi County Hospital Road,
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya KEMRI CGMRC
Role Name Email Phone Street address
Scientific Enquiries Philip Bejon PBejon@kemri-wellcome.org +254709983549 Centre for Geographic Medical Research Coast Kilifi County Hospital Road,
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya KEMRI CGMRC
Role Name Email Phone Street address
Public Enquiries Mainga Hamaluba MHamaluba@kemri-wellcome.org +254709983946 Centre for Geographic Medical Research Coast Kilifi County Hospital Road,
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya KEMRI CGMRC
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual-level anonymized data will be shared with the sponsor. We will make the information on antigen prioritization publicly available and open access with respective publication(s) on a data repository according to the KEMRI-CGMRC data governance guidelines to provide the widest possible benefit of the study. For wider stake-holder engagement and the research community, summary-level statistical analyses will be shared. Information collected or generated during this study will be pseudo-anonymised for use to support new research on malaria vaccines. Any future research using information and samples from this study must first be approved by a local or national expert committee to make sure that the interests of participants and their communities are protected. Data and sample access will be managed by KEMRI-CGMRC. Study Protocol 15 years Data will be made available including data dictionaries after de-identification of volunteers. The data will be available to researchers who submit requests to dgc@kemri-wellcome.org to gain access to the data following a signed data access agreement.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information