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.: PACTR202303893454050 Date of Approval: 29/03/2023
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Fractional Dose Yellow Fever Vaccination in Gambian Infants
Official scientific title A phase 3, randomized, active-controlled, observer-blind trial to assess the safety and immunogenicity of subcutaneous (SC) and intradermal (ID) fractional dose yellow fever vaccination (YFV), and the impact of measles and rubella vaccine (MRV) co-administered, in nine-month-old infants in The Gambia.
Brief summary describing the background and objectives of the trial This is a phase 3, single-centre, observer-blind, randomized, active-controlled trial. Following community and individual sensitization, informed consent, and screening for eligibility, 1300 healthy infants who are at least nine months, but less than 12 months of age will be recruited and randomized to one of five groups. The trial objectives are: -To assess whether two fractional doses of a YFV, administered with an interval of nine months, result in immune responses that are superior to the immune responses generated by a single, SC, full dose of a YFV and whether this is influenced by the ID or SC route of fractional-dose vaccine administration. -To assess whether fractional doses of a YFV administered by the ID route results in superior immune responses to fractional dose administered by the SC route.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Yellow Fever
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 01/05/2023
Actual trial start date
Anticipated date of last follow up 01/05/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 1300
Actual target sample size (number of participants)
Recruitment status 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
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Outcome Assessors
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Measles and Rubella Vaccine Single dose 0.5ml Only visit 1 The vaccine is lyophilised and provided with a diluent. The vaccine has the appearance of a yellowish-white dry cake in its lyophilised form. The vaccine should be reconstituted only with the entire diluent supplied (sterile water for injection) using a sterile needle and syringe. With gentle shaking the dried cake should dissolve easily. The vaccine is supplied as a single dose vial. Thus, a new vial will be used for each participant. 200 Active-Treatment of Control Group
Experimental Group Yellow fever Vaccine Group 1: full yellow fever dose (0.5ml) subcutaneous Group 2: fractional dose(0.1ml)Intradermal Group 3 and 4: fractional dose(0.1ml)subcutaneous Groups 1, 2, 3: Single dose at Visit 1 and Visit 3 Group 4 : Single dose at Visit 1 The vaccine is provided in a 1 dose pre-filled syringe (1 x 0.5 mL). The vaccine is provided in a lyophilized form in a vial which must be reconstituted with the diluent in the pre-filled syringe before use 1100
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
A prospective participant must meet all the following inclusion criteria to be eligible for enrolment (randomization and vaccination): Participants must: • Have voluntary written/thumb-printed informed consent provided for them by a parent Be nine- to <12 months-of-age on the day of randomization and vaccination (i.e., enrolment). They will be eligible from the day they reach nine months of age until the day before they reach 12-months-of-age. The identity and age of all prospective participants must be as confirmed from the Infant Welfare Card (IWC) prior to informed consent. Participants/parents will be issued with a trial photographic identification card once randomization and vaccination has taken place (V1). • Have a parent who is judged to be able to comprehend and comply with study requirements and procedures and is willing and able to return for all scheduled follow-up visits. • Have a parent who is willing to ensure they avoid oral consumption of herbal or other local traditional medications throughout the course of the study. Also, who is willing to ensure they avoid the use of medications (for example those available for purchase at local pharmacies) except those provided by the trial team (unless in an emergency). • Have a readily identifiable place of residence within a reasonable travelling distance of the clinical trial site. This aims to ensure home visits for solicited AE can be undertaken reliably and that the participant is able to present to the trial site or be reviewed at their home in the event of other unsolicited health complaints. No specific geographical limits are set with this regard. Rather such decisions will be made based on the judgement of senior members of the field team based on their detailed knowledge of local geography and transport links. • Have a parent with a consistent means of telephone contact for the duration of trial participation. • Have a parent who is willing to ensure the participant does not receive additional YFV • Used any investigational product within the 90 days prior to study vaccination or plan to use any investigational products during the period of study participation. • Consumed (by ingestion) any herbal or other traditional medication within 14 days of study product administration. • History of serious reactions to any prior vaccination or known hypersensitivity to any component of the YFV and or MRV • History of anaphylactic shock or other life-threatening allergic reactions • Any chronic, clinically significant abnormality or illness that requires medical therapy. • Administration of any vaccines within 28 days before trial vaccination. • History of chronic administration of immunosuppressant or other immune modifying drugs within the 12 months prior to the administration of the study vaccine. • History of the administration of immunoglobulins and/or any blood products or anticipation of such administration during the study period. • History of known disturbance of coagulation or blood disorder that could cause anaemia or excess bleeding. • Any medical or social condition that in the opinion of the study clinician may interfere with the study objectives, pose a risk to the participant or prevent the participant from completing the study follow-up. • Employee of, or direct descendant of any person employed by the investigator or sponsor. • Plans to travel outside the study area for an extended duration during the period of study participation. • Any vital sign with a toxicity score of > 1 • Have HIV or have been vertically exposed to HIV based on maternal history (mothers of potential participants will not be tested for HIV as part of screening but will be specifically asked and their antenatal card reviewed when available for evidence of testing. • Have a weight for height z-score below -3SD (severe malnutrition) • Have been vaccinated against yellow fever, measles, or rubella. Infant: 13 Month(s)-24 Month(s) 9 Month(s) 12 Month(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 30/05/2022 LSHTM Ethics
Ethics Committee Address
Street address City Postal code Country
Keppel Street, London WC1E 7HT London WC1E 7HT United Kingdom
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 01/12/2022 The Gambia Government MRC Joint Ethics Committee
Ethics Committee Address
Street address City Postal code Country
MRC Unit The Gambia at LSHTM , Atlantic Boulevard Fajara, The Gambia West Africa Banjul P.OBox273 Gambia
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Yellow fever neutralizing antibody titres based on plaque reduction neutralization test (PRNT50) 10 months of age plus 28 days after enrolment
Primary Outcome Measles IgG binding antibody concentration 10 months of age plus 28 days after enrolment
Primary Outcome Rubella IgG binding antibody concentration 10 months of age plus 28 days after enrolment
Secondary Outcome Rates of yellow fever seroconversion 18 months of age plus 280 days after enrolment
Secondary Outcome Rates of measles seroconversion 18 months of age plus 280 days after enrolment
Secondary Outcome Rates of rubella seroconversion 18 months of age plus 280 days after enrolment
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
MRCG at LSHTM Atlantic Boulevard, Fajara Banjul Gambia
FUNDING SOURCES
Name of source Street address City Postal code Country
Medical Research Council United Kingdom 2nd Floor David Phillips Building, Polaris House, North Star Avenue, Swindon Swindon SN2 1FL United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor London School of Hygiene and Tropical Medicine Keppel street, London WC1E 7HT London United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Sidat Fofana EPI Programme Manager Ministry of Health The Quadrangle Banjul Gambia
J Erin Staples Division of Vector-Borne Diseases Centers for Disease Control and Prevention Fort Collins Colorado CO 80521 United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Ed Clarke ed.clarke@lshtm.ac.uk 002207039732 Atlantic Boulevard
City Postal code Country Position/Affiliation
Banjul Gambia Vaccines and Immunity Theme
Role Name Email Phone Street address
Scientific Enquiries Armel Zemzi armel.zemsi@lshtm.ac.uk +2203132935 Atlantic Boulevard, Fajara
City Postal code Country Position/Affiliation
Banjul Gambia Head of Clinical Trials Unit
Role Name Email Phone Street address
Public Enquiries Ed Clarke ed.clarke@kshtm.ac.uk +2207039732 Atlantic Boulevard, Fajara
City Postal code Country Position/Affiliation
Banjul Georgia Vaccines and Immunology
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Anonymised IPD data will be made available from one month after trial publication and for a further 24 months Informed Consent Form,Study Protocol 1 month after the publication date and for a further 24 months Application to the principal investigator with a valid scientific proposal to be reviewed at an institutional level.
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