Non- Inferiority Fractional-doses Trial for Yellow Fever Vaccine

OxTREC Ref: 2-19

In the recent past there has been a number of large urban Yellow Fever outbreaks in sub-Saharan Africa, tropical South Americas, The demand for Yellow Fever vaccines in response to the large urban outbreaks occurring concurrently and the risk of further spread through Africa and to Asia was larger than the available global supply. In this situation, the World Health Organisation (WHO) developed recommendations for the use of fractional doses of Yellow Fever vaccine as a dose-sparing strategy. These recommendations were based on data from a limited number of clinical trials, none of which had been conducted in Africa. This was due to the uncertainties on the minimum dose requirement. Our study complements a study which is comparing full standard dose to 1/5th of standard dose of all four WHO-prequalified YF vaccines in adults (ClinicalTrials.gov number: NCT02991495), and is currently ongoing at KEMRI CGMRC and Epicentre, Mbarara which is designed to answer questions on the use of current stock of YF vaccines with a potency as close as possible to each manufacturers' minimum release. Data from this trial will inform a WHO recommendation on using 1/5th of the current standard dose of vaccine for outbreak control. However, since many vials will contain excess YF vaccine such that 1/5th of a vial is likely to be substantially above the current minimum potency requirements, these data may not be scientifically explanatory regarding the minimum dose required for preventive use. The new complementary study, aims to determine the lowest YF vaccine dose that is non-inferior to the current standard full dose among populations in sub-Saharan Africa. The study will be conducted in Kenya (KEMRI Center for Geographical Medicine Research-Coast (CGMR-C), Kilifi) and Uganda (Epicentre, Mbarara) with trial participants recruited at both sites, using vaccine from one WHO-prequalified manufacturer (Institut Pasteur de Dakar, Senegal (IPD)).

2019-11-11

2020-03-30

2023-06-24

Completed

Early phase I

900

Inclusion Criteria: * Individuals aged ≥18 - \<60 years of age. * Children aged between 9 months and 12 months. * HIV negative on serological screening OR HIV positive adults and children aged \> 18 months on serological testing, and no symptoms suggestive of current clinical immunosuppression and cluster of differentiation-4 (CD4) count\>200 (for adults) and CD4% \> 25% (for children aged 9-12 months) within the last 6 months. * Ability to provide informed consent to participate in the study Exclusion Criteria: * Known contraindications to YF vaccination such as allergies to egg protein and chicken products or any component of the vaccine (including gelatin, eggs, eggs products or chicken products), immunodeficiency, known thymus disorder, such as thymoma and myasthenia gravis * Using corticosteroids or other immunosuppressive therapy * Thymus disorder, such as thymoma and myasthenia gravis * Acute febrile disease on the day of vaccination with temperature \>37.5 degrees Celsius is a temporal contraindication. * Previous YF vaccination * Previous YF infection as determined from history * Pregnancy (as determined by a urine test on the proposed day of vaccination) and lactating women * Planning to migrate out of the study areas before the end of the study follow-up * Planning to travel to a country requiring YF vaccination certificate within the first year after vaccination. * Any condition or criteria, including acute or chronic clinically significant abnormality that in the opinion of the investigator might compromise the wellbeing of the volunteer or interfere with the outcome of the study.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE4'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Adult participants (n=480) will be randomized for vaccination with full standard dose or with 1000, 500 or 250 IU (i.e. 4 arms) with a 1:1:1:1 allocation ratio. Results for the safety and primary outcome of the adult study will then be reviewed by the DSMB, and the lowest non-inferior dose in the adult study selected for assessment in children aged 9 months to 5 years (n=420) in comparison to full standard dose (i.e. 2 arms) with a 1:1 allocation ratio.', 'primaryPurpose': 'PREVENTION', 'maskingInfo': {'masking': 'TRIPLE', 'maskingDescription': "Investigators and participants will be blinded to the allocations. Only the pharmacist and the nurse administering the vaccine will be unblinded. The allocation will be to one of the four treatment arms per a computer-generated randomization schedule. Allocations will be concealed until a member of the unblinded study team scratches the randomization booklet to reveal the participants' randomization arm.", 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 900, 'type': 'ACTUAL'}}

2024-02-09