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.: PACTR202105682956280 Date of Approval: 24/05/2021
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title A study to determine if a new malaria vaccine is safe and induces immunity among Kenyan adults, young children and infants.
Official scientific title A Phase 1b, open-label, age de-escalation, dose-escalation study to evaluate the safety and immunogenicity of different doses of a candidate malaria vaccine; adjuvanted R21(R21/MM) in adults, young children and infants in Kilifi, Kenya.
Brief summary describing the background and objectives of the trial Currently, RTS,S/AS01E is the most advanced malaria vaccine. However, the vaccine demonstrated moderate efficacy against clinical malaria in infants (28.3%; 95% CI 23.3-32.9) aged 6-12 weeks who received 3 vaccinations 4 weeks apart with or without a booster vaccination at 20 months. Implementation of the vaccine is currently under evaluation in Kenya, Malawi and Ghana to establish impact. R21/MM also induces a good immune response, is cheap and easy to make and as such there is a good case for further clinical development of this vaccine. Malaria deaths have fallen with the advent of new drug combinations and widespread use of insecticide treated bed nets but the hope malaria eradication is threatened by emerging resistance to these drugs and insecticides. One of the primary strategic goals outlined by WHO in the Malaria Vaccine Roadmap, is the development of malaria vaccines which would protect against clinical malaria in 3 out of 4 vaccinated individuals, and would be suitable for administration in malaria endemic areas and appropriate at-risk groups by 2030.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) VAC073
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 28/04/2019
Actual trial start date 28/04/2019
Anticipated date of last follow up 31/07/2022
Actual Last follow-up date 31/07/2022
Anticipated target sample size (number of participants) 91
Actual target sample size (number of participants)
Recruitment status Closed to recruitment,follow-up continuing
Publication URL
Secondary Ids Issuing authority/Trial register
NCT03580824 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 Non-randomised Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group R21 Matrix M The participants received 3 primary doses 4 weeks apart with a booster dose at 9-25 months post the third dose. The following doses were given: Full dose (10µgR21/50µMM), Half dose (5µgR21/25µgMM), and Intermediate (5µgR21/50µgMM). 2years 5months R21: Protein particle malaria vaccine candidate in Matrix-M: Saponin based vaccine adjuvant. The R21 drug product is presented in sterile 2mL glass vials at a target concentration to allow the extraction of a single dose from each vial. Matrix-M is presented in sterile 2mL glass vials at a concentration of 0.375 mg/mL with a fill volume of 0.75mL. 91
Control Group No Control This is an open label Trial with no control group This is an open label Trial 0 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Healthy adults aged 18 to 45 years (Group 1), Healthy child aged 1-5 years (Group 2), healthy infant aged 5- <12 months (Group 3) • 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 duration of study for female participants. 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 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) • Adults with a Body Mass Index (BMI) 18 to 30 Kg/m2; or young children and infants with Z-score of weight-for-age within ±3SD • Provide written informed consent • Plan to remain resident in the study area for 2 years following last dose of vaccination • Clinically significant congenital abnormalities as judged by the study clinician. • 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. • 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). • Any significant disease, disorder or situation 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. Adult: 19 Year-44 Year,Infant: 0 Month(s)-12 Month(s),Infant: 13 Month(s)-24 Month(s),Middle Aged: 45 Year(s)-64 Year(s),Preschool Child: 2 Year-5 Year 5 Month(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 26/09/2018 Scientific Ethics Research Unit
Ethics Committee Address
Street address City Postal code Country
P.O. BOX 54840 OFF MBAGATHI ROAD, NAIROBI, KENYA HOUSE NUMBER 8, KEMRI HEADQUARTERS. Nairobi 00200 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome 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 • Occurrence of solicited local reactogenicity signs and symptoms for 7 days following the vaccination • Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following the vaccination • Occurrence of unsolicited adverse events for 28 days following the vaccination • Change from baseline for safety laboratory measures • Occurrence of serious adverse events during the whole study duration Throughout the Trial
Secondary Outcome • Comparison of immunogenicity (antibody responses) of the R21/MM vaccination doses and the longevity of responses Throughout the trial
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
KEMRI WELLCOME TRUST RESEARCH PROOGRAMME CENTRE FOR GEOGRAPHIC MEDICINE COAST HOSPITAL GROUNDS OFF BOFA ROAD P.O BOX 230 KILIFI KENYA 80108 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
European and developing countries clinical trials partnership P.O. Box 93015 2509 AA The Hague Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Oxford University of Oxford, University Offices, Wellington Square, Oxford, OX1 2JD, UK Oxford United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Scientific Enquiries Philip Bejon PBejon@kemri-wellcome.org +254709983000 KEMRI WELLCOME TRUST RESEARCH PROGRAMME CGMRC P.O Box 230
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya Executive Director
Role Name Email Phone Street address
Principal Investigator Mainga Hamaluba MHamaluba@kemri-wellcome.org +254709983946 KEMRI WELLCOME TRUST RESEARCH PROGRAMME CGMRC P.O 230
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya Principal Investigator
Role Name Email Phone Street address
Public Enquiries Marianne Munene MMunene@kemri-wellcome.org +254709983436 KEMRI WELLCOME TRUST RESEARCH PROGRAMME CGMRC
City Postal code Country Position/Affiliation
Kilifi 80108 Kenya Research Governance Manager
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 stakeholder engagement and the medical community, summary-level statistical analyses will be shared. Information collected or generated during this study may be anonymised for use to support new research on coronavirus vaccines and immunology. Any future research using information 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 KEMRI CGMRC. Analytic Code,Informed Consent Form,Statistical Analysis Plan,Study Protocol At the end of the Study On completion of the trial and submission of the manuscript. De-identified trial data that underlies the results reported in the publication will be uploaded onto the KWTRP data repository on Harvard Dataverse as per the curation policy. This data will be uploaded under managed access. Requests for access to data will be submitted via email through a form available on the repository and reviewed by the KWTRP Data Governance Committee (DGC) who will also determine whether further approvals are required before data is shared.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://wellcome.ac.uk/grant-funding/guidance/data-software-materials-management-and-sharing-policy 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