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.: PACTR202407803870883 Date of Approval: 11/07/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Phase I open-label, age de-escalation trial to assess safety, tolerability, and immunogenicity of the intramuscularly administered combination of RH5.1 and R78C malaria vaccine with Matrix-MTM adjuvant in healthy adults and infants in Tanzania.
Official scientific title Phase I open-label, age de-escalation trial to assess safety, tolerability, and immunogenicity of the intramuscularly administered combination of RH5.1 and R78C malaria vaccine with Matrix-MTM adjuvant in healthy adults and infants in Tanzania.
Brief summary describing the background and objectives of the trial Malaria is still one of the global health challenges that require better solutions. Although focused efforts have led to substantial reductions in morbidity and mortality worldwide, progress has now stalled. Vaccines have significantly reduced the global all-cause child mortality and an effective malaria vaccine is needed to complement other interventions to further control and eventually eliminate malaria disease. RH5.1 vaccine has been evaluated in a Phase I/IIa clinical trial in healthy UK adults formulated in GSK’s adjuvant AS01B (61). The RH5.1/AS01B formulation was administered using a range of RH5.1 protein vaccine doses (2, 10, and 50 μg) and was found to be safe and well tolerated. A regimen using a delayed and fractional third dose, in contrast to three doses given at monthly intervals, led to significantly improved antibody response longevity over ∼2 years of follow-up. Subsequently, RH5.1 was re-formulated in Matrix-M adjuvant from Novavax and has entered a Phase Ib age de-escalation safety and immunogenicity trial at the Ifakara Health Institute (IHI), Tanzania in a trial funded by the EDCTP Multi-Stage Malaria Vaccine Consortium (MMVC) (ClinicalTrials.gov NCT04318002). This trial will also assess monthly vs delayed vs delayed-fractional dosing regimens to measure IgG longevity in the target age group for a blood stage vaccine (given the success seen in the UK trial with the AS01B formulation. The new pre-clinical evidence of the improved potency of immune responses following co administration of RH5.1 and R78C in rats, provides the scientific basis to initiate early human trials to assess the safety and immunogenicity of RH5.1+Ripr-CyRPA combination vaccine. The combination is expected to improve the GIA of the induced antibodies, an outcome that could imply better in-vivo protection against malaria. The study will provide insights on the safety and immunogenicity of the combined vaccination and compare between co- administration of the RH5.1 and R78C.1. Primary Objectives • To determine safety and tolerability of RH5.1 and R78C vaccine in Matrix- M co-administered intramuscularly in adults (18-45 years), and infants (5- 17 months) residing in a malaria endemic country. 2. Secondary objectives • To evaluate the magnitude of humoral immune responses to RH5.1, and R78C co-administered intramuscularly in adults and infants residing in a malaria endemic country. • To evaluate the quality of humoral immune responses to RH5.1, and R78C co-administered intramuscularly according to 0,1,6 or 0,1,6,7-month schedule in adults and infants residing in a malaria endemic country. • To evaluate the longevity of humoral immune responses to RH5.1, and R78C co-administered intramuscularly in adults and infant. 3. Exploratory Objectives • To evaluate cellular immune responses to RH5.1, and R78C. • To assess the impact of iron status on the vaccine immune responses
Type of trial Non-Randomised
Acronym (If the trial has an acronym then please provide) BIO003
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Treatment: Drugs
Anticipated trial start date 15/07/2024
Actual trial start date 29/07/2024
Anticipated date of last follow up 30/07/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 60
Actual target sample size (number of participants)
Recruitment status Active, not recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
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
Crossover: all participants receive all interventions in different sequence during study Non-randomised 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 Intervention Group Three to four intramuscular vaccine injection of R78C alone or in combination with RH5.1 in Matrix-M will all be administered intramuscularly into the deltoid area for adults and anterolateral thigh for infants. 10μg RH5.1,10 μg R78Cand 50μg Matrix M as an adjuvant. 13 months The RH5.1 and R78C vaccines will be shipped from Oxford on dry ice, and then stored at –80°C (nominal) in a freezer that will be in a secure pharmacy until required. Matrix-M adjuvant will be shipped by the manufacturer and will be stored between +2 and +8°C in a fridge. Matrix-M™ adjuvant is manufactured by Novavax AB, Matrix-M is a slightly brown to colourless slightly opalescent non-viscous liquid. 60
Control Group Control Group Three vaccine injections of 10μg R78C and 50μgMatrix-M on 0,1,6 regime. 12 months Ripr and CyRPA have recently been developed by the Draper’s group at the University of Oxford and has been manufactured to GMP standard at GenIbet in Portugal. R78C vaccines will be shipped from Oxford on dry ice, and then stored at –80°C (nominal) in a freezer that will be in a secure pharmacy until required. Matrix-M adjuvant will be shipped by the manufacturer and will be stored between +2 and +8°C in a fridge. 30 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Healthy adults aged 18 to 45 years and infants aged 5-17 months 2. Adults and parents able and willing (in the Investigator's opinion) to comply with all study requirements 3. Permanent residence or planned long term stay (at least 15 months) in the study area or surroundings for the period of the trial. 4. Female participants are required to use an effective form of contraception during this study. Acceptable forms of contraception include: a. Established use of oral, injected or implanted hormonal methods of contraception. b. Placement of an intrauterine device or intrauterine system c. Total abdominal hysterectomy 5. For adults: Written informed consent to receive malaria vaccine candidates 6. For infants: written informed consent to receive malaria vaccine candidates will be obtained from the parent/guardian. 7. Reachable (24 hours and 7 days a week) by mobile phone during the entire study period (From screening to last follow up visit) 8. Answer all questions on the informed consent quiz correctly in a maximum of three attempts. Any history, or evidence at screening, of clinically significant symptoms, physical signs or abnormal laboratory values suggestive of systemic conditions, such as cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine, malignant, haematological, infectious, immunodeficient, psychiatric and other disorders, which could compromise the health of the participant during the study or interfere with the interpretation of the study results. 2. Use of immunoglobulins or blood products within 3 months prior to enrolment 3. Previous vaccination with a Malaria vaccine. 4. Pregnancy (determined by positive urine pregnancy test), lactation, or intention to become pregnant during the study. 5. Any other serious chronic illness requiring hospital specialist supervision 6. Volunteers unable to be closely followed for social, geographic, or psychological reasons 7. Positive for P. falciparum parasites by Blood smear at screening or previous participation in any malaria vaccine study. 8. Any other condition or situation that would, in the opinion of the investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol. 9. Clinically significant congenital abnormalities as judged by the PI or other delegated individual. 10. History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, e.g., Kathon, neomycin, beta-propiolactone 11. Any history of anaphylaxis in relation to vaccination. 12. Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period. 13. Scheduled elective surgery or other procedures requiring general anaesthesia during the trial. Adult: 19 Year-44 Year,Infant: 0 Month(s)-12 Month(s) 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 11/04/2023 IHIIRB
Ethics Committee Address
Street address City Postal code Country
78373 Dar es salam Dar es salam 78373 United Republic of Tanzania
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 31/07/2023 NIMR
Ethics Committee Address
Street address City Postal code Country
3 Barack Obama Drive Daressalam 9653 Tanzania
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome To determine safety and tolerability of RH5.1 and R78C in Matrix-M co-administered intramuscularly in adults (18-45 years), and infants (5-17 months) residing in a malaria endemic country. 28 days post each dose.
Secondary Outcome 1. To evaluate the magnitude of humoral immune responses to RH5.1 and R78C co-administered intramuscularly in adults and infants residing in a malaria endemic country. • To evaluate the functional quality of humoral immune responses to RH5.1 and R78C co-administered intramuscularlyaccording to 0,1,6 and 0,1,6,7-month schedule in adults and infants residing in a malaria endemic country. • To evaluate the longevity of humoral immune responses to RH5.1 and R78Cco-administered intramuscularly in adults and infants residing in a malaria endemic country. Avidity of RH5.1, and R78C antibodies by ELISA.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Bagamoyo Clinical Trial Facility Kingani- Bagamoyo Pwani 74 United Republic of Tanzania
FUNDING SOURCES
Name of source Street address City Postal code Country
The European and Developing Countries Clinical Trials Partnership Anna van Saksenlaan 51, 2593 HW Den Haag, Netherlands The Hague 2593 Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Ifakara Health Institute Kingani Bagamoyo Pwani 74 United Republic of Tanzania NGO
COLLABORATORS
Name Street address City Postal code Country
Dr. Angela Minassian Churchill Hospital Old Road Oxford OxFORD OX3 7LJ United Kingdom
Prof Simon J Draper South Parks Road Oxford OxFORD OX1 3QU United Kingdom
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Ally Olotu aolotu@ihi.or.tz +255718927104 Kingani Bagamoyo
City Postal code Country Position/Affiliation
Pwani 74 United Republic of Tanzania Principal Investigator
Role Name Email Phone Street address
Public Enquiries Ainaekisha Kahatano akahatano@ihi.or.tz +255753566076 Kingani Bagamoyo
City Postal code Country Position/Affiliation
Pwani 74 United Republic of Tanzania Co Principal Investigator
Role Name Email Phone Street address
Scientific Enquiries Maximillian Mpina mmpina@ihi.or.tz +255788360101 Kingani Bagamoyo
City Postal code Country Position/Affiliation
Pwani 74 United Republic of Tanzania Scientist
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The study protocol, documentation, data and all other information generated will be held in strict confidence. No information concerning the study or the data will be released to any unauthorized third party, without prior written approval of the trial sponsor. Analytic Code,Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol The site owns the data and it is agreed that these will be shared or publication in a timely manner during the 20 years all biological and study material will be stored securely at permanent Archive at IHI-Kingani as per TMDA Guidlines. No information concerning the study or the data will be released to any unauthorized third party, without prior written approval of the trial sponsor.
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