A Phase I/II, Double-blind, Randomized, Active-controlled, Age De-escalation Trial to Assess Safety and Immunogenicity of a Measles Rubella Vaccine (MRV) Microneedle Patch (MRV-MNP) in Adults, MRV-primed Toddlers, and MRV-naïve Infants
This is a phase 1/2, single-centre, double-blind, double-dummy, randomized, active-controlled, age de-escalation trial. Age de-escalation will be based on a review of the safety data from the preceding cohort (adults for toddlers and toddlers for infants) up to day 14 post study product administration by a data monitoring committee (DMC). All participants will receive either the MRV-MNP and a placebo (0.9% sodium chloride) SC injection (PLA-SC) or a placebo-MNP (PLA-MNP) and MRV by the SC route (MRV-SC). Only those study staff randomizing participants and preparing the study products for administration will be aware of the products administered. Those administering the study products, all other trial staff and the participants and parents will be blinded to treatment group. 45 adults (18 to 40-years-of-age) will be randomized in a 2:1 ratio. Thus, 30 adults will receive MRV-MNP and PLA-SC while 15 adults will receive MRV-SC and PLA-MNP. 120 toddlers (15 to 18 months-of-age) will be randomized in a 1:1 ratio. Thus, 60 toddlers will receive MRV-MNP and PLA-SC while the same number of toddlers will receive MRV-SC and PLA-MNP. 120 infants (9 to 10 months) will also be randomized in a 1:1 ratio. Thus, 60 infants will receive MRV-MNP and PLA-SC while the same number of infants will receive MRV-SC and PLA-MNP. Solicited local and systemic AE will be collected daily from all participants from the day of study product administration to day 13 post study product administration. Unsolicited AE and SAE will be collected from the day of study product administration to day 180 post study product administration. All participants will have laboratory investigations (hepatitis B, hepatitis C, hematology and biochemistry) conducted as part of screening. Adults will have safety laboratory investigations repeated on day seven and day 14 post study product administration. Toddlers and infants will have safety laboratory investigations repeated on day seven post study product administration. All participants will have measles- and rubella-specific SNA titers and measles- and rubella-specific IgG concentrations measured at baseline and day 42 and 180 post study product administration. Other Expanded Program on Immunization (EPI) vaccines due in toddler (oral poliovirus vaccine, diphtheria-tetanus-pertussis) and in infants (oral poliovirus vaccine, yellow fever vaccine and MenAfriVac® [due at 12 months]) will be given by the investigator team at the day 42 study visit (V4).
• Adults: Be between 18 and 40 years inclusive on the day of consent.
• Toddlers: Be between 15 and 18 months of age inclusive on the day of consent.
• Infants: Be between 9 and 10 months of age inclusive on the day of consent.
• Be judged to be able to comprehend and comply with study requirement and procedures and must be willing and able to return for all scheduled follow-up visits (adult cohort).
• Have a parent who is judged to be able to comprehend and comply with study requirement and procedures and is willing and able to return for all scheduled follow-up visits (toddler and infant cohort).
• Be willing to avoid consumption (ingestion and topical application) of herbal or other local traditional medications throughout the course of the study.
• Have a readily identifiable place of residence within a reasonable travelling distance of the clinical trial site.
• Have a consistent means of telephone contact for the duration of trial participation
• Have a site on one wrist that is judged to be suitable for MNP administration.
• Adult female cohort only: have a negative serum pregnancy test at screening (V0) and negative urine pregnancy test on the day of vaccination (V1).
• Adult female cohort only: employ an effective method of birth control for two months preceding and throughout the study
• Toddler cohort only: have been parenterally vaccinated against measles and rubella at between nine and 12 months of age.