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.: PACTR202108505632810 Date of Approval: 24/08/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A study to determine if candidate malaria vaccines are safe, effective, and induce immunity among Kenyan adults.
Official scientific title Safety, immunogenicity, and efficacy of R21/Matrix M (R21/MM) and ChAd63/MVA-ME-TRAP in the context of controlled human malaria infection: A Phase IIb Trial in Kenyan Adults.
Brief summary describing the background and objectives of the trial Malaria deaths have fallen with the advent of new drug combinations and widespread use of insecticide treated bed nets, but the hope of malaria eradication is threatened by emerging resistance to these drugs and insecticides. RTS,S, is the only malaria vaccine in advanced clinical development albeit with low efficacy. It is being evaluated for use in an infant vaccine schedule recommended by WHO, while determining the significance of any safety concerns. However, with RTS,S only a small proportion of the vaccine is made up of the malaria parasite protein. We have developed a malaria vaccine candidate, R21, which is also based on the same protein in RTS,S. The majority of RTS,S is composed of the Hepatitis B surface protein which may interfere with the immune response in infants; whereas R21 has very little of this protein on its surface. R21 also induces a good immune response and there is a good case for further clinical development of this vaccine.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) VAC074
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 01/09/2021
Actual trial start date
Anticipated date of last follow up 28/02/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 84
Actual target sample size (number of participants) 84
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
NCT03947190 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 R21 MM PfSPZ Challenge 10µg R21 /50µg Matrix M vaccine 22,500 PfSPZ Challenge ID 56 days R21 MM and 21 days PfSPZ Challenge R21: Protein particle malaria vaccine candidate in Matrix-M: Saponin based vaccine adjuvant. PfSPZ Challenge: cryopreserved Plasmodium falciparum sporozoites. 24
Experimental Group ChAd63 MVA METRAP 5x10^10 vp ChAd63 ME-TRAP and 2x10^8 pfu MVA ME-TRAP 22,500 PfSPZ Challenge ID 56 days ChAd63 MVA METRAP 21 days PfSPZ Challenge ChAd63, chimpanzee adenovirus serotype 63; ME-TRAP, multiple epitope string fused to the thrombospondin-related adhesion protein; MVA, modified vaccinia Ankara. PfSPZ Challenge: cryopreserved Plasmodium falciparum sporozoites. 24
Control Group None None None None 18 Placebo
Experimental Group R21 MM PfSPZ Challenge 10µg R21 /50µg Matrix M vaccine 3,200 PfSPZ Challenge DVI 56 days R21 MM and 21 days PfSPZ Challenge R21: Protein particle malaria vaccine candidate in Matrix-M: Saponin based vaccine adjuvant. PfSPZ Challenge: cryopreserved Plasmodium falciparum sporozoites. 14
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 • Non-pregnant, non-lactating adult female or adult male • Agreement to refrain from blood donation during the study • Use of effective method of contraception for the duration of study for female participants. For those with no contraception, they will be referred for contraception at the relevant health facility. For female participants, we will ask them to attend with their family planning records for verification. 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 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) • Provide written informed consent • Plan to remain resident in the study area for 1 year following first dose of vaccination • Clinically significant congenital abnormalities as judged by the study clinicians • 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). • Sickle cell disease • Any history of anaphylaxis in relation to vaccination • Clinically significant laboratory abnormality as judged by the study clinician • Blood transfusion within one month of enrolment • Haemoglobin less than 11.3 g/dl for men and less than 10g/dl for in women, where judged to be clinically significant in the opinion of the investigator. • Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate • Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period
 • Seropositive for hepatitis B surface antigen (HBsAg) or hepatitis C (HCV IgG) • 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) • Women only; pregnancy, or an intention to become pregnant a day before challenge i.e. at C-1 • Any significant disease, disorder or situation (including confirmed COVID-19 PCR positivity) which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial • Confirmed parasite positive by PCR a day before challenge i.e. at C-1. • Confirmed PCR positive for COVID-19 three days before challenge i.e. C-3. 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 29/05/2019 SERU
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 08/08/2019 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 The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events. The following parameters will be assessed for all study groups 1. Occurrence of solicited local reactogenicity signs and symptoms for 7 days following the vaccination 2. Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following the vaccination 3. Occurrence of unsolicited adverse events for 28 days following the vaccination 4. Change from baseline for safety laboratory measures 5. Occurrence of serious adverse events during the whole study duration including safety with regards to PfSPZ Challenge administration. 21 days post challenge
Primary Outcome Efficacy Venous blood samples will be taken at each study visit during the post-CHMI follow-up period as described above for quantitative PCR (qPCR) for P. falciparum nucleic acids which will be processed within 6 hours of collection. A diagnosis of malaria infection will be made and treatment with anti-malarials commenced immediately for a volunteer satisfying one of the following criteria: 1. The density of infection rises past a threshold of 500 parasites per µl 2. The volunteer develops symptoms or signs of illness and an immediate blood film examination shows any evidence of detectable malaria parasites 3. The volunteer reaches day 21 of monitoring, at which point CHMI will be completed The investigators are able to treat any volunteer for malaria regardless of the qPCR result if they are clinically concerned (and have discussed the case with the Chief Investigator), or a volunteer wishes to withdraw from the study. 21 days post challenge
Secondary Outcome Immunology 1. Comparison of immunogenicity (antibody responses) of the R21/MM vaccination doses and the longevity of responses 90 days post challenge
Secondary Outcome Efficacy Further measures of vaccine efficacy will be used, as secondary endpoints, to provide more detailed quantitative assessment of the dynamics of malaria infection in sporozoite-challenged volunteers. These measures enable more powerful distinction, than the use of sterile efficacy rates, between the performance of different vaccination regimens, and between individuals receiving the same vaccination regimen, as has been shown for previous efficacy trials. This maximises the yield of information from the volunteers in this study that is used to assess the primary objective. 21 days post challenge
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 Referral Hospital Road KILIFI 80108 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
EDCTP 2509 AA Hague Netherlands
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
The Jenner Institute Roosevelt Drive Oxford OX3 7DQ United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Melissa Kapulu mkapulu@kemri-wellcome.org +254709983463 Off Bofa Road
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya KEMRI CGMRC Wellcome Trust Research Programme
Role Name Email Phone Street address
Scientific Enquiries Philip Bejon pbejon@kemri-wellcome.org +254709983549 Off Bofa Road
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya KEMRI CGMRC Wellcome Trust Research Programme
Role Name Email Phone Street address
Public Enquiries Mainga Hamaluba mhamaluba@kemri-wellcome.org +254709983946 Off Bofa Road
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya KEMRI CGMRC Wellcome Trust Research Programme
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual-level anonymized data will be shared with the sponsor. For wider stake-holder engagement and the medical community, summary-level statistical analyses will be shared. Information collected or generated during this study will be de-indentified for use to support new research on malaria vaccines. Long term storage of samples (15 years) will be undertaken at KEMRI-CGMRC in Kilifi with only aliquots of samples being shared with collaborators. 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 will be managed by KWTRP. Study Protocol 2 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