Clinical trial NCT06667206: Earlier Prime-BOOST Schedule to Improve MEasles Protection in High Burden Settings
Official title: Earlier Prime-BOOST Schedule to Improve MEasles Protection in High Burden Settings
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Measles
Keywords: measles-rubella vaccine
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: St George's, University of London
name: MU-JHU CARE
First posted: 2024-10-31
Enrollment: 450
Sex: ALL
Minimum age (years): 23
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Equal numbers of participants are randomised to 3 arms.
Primary purpose: PREVENTION

Brief summary: This is a phase IIb clinical trial investigating the non-inferiority of immune responses in children given two doses of measles vaccine at different timepoints. The study will randomise 450 children to 3 groups: group A will receive measles containing vaccine (MCV) at 6 and 12 months ; group B at 9 and 18 months; Group C at 6 and 18 months.

Detailed description: Two doses of measles containing vaccine (MCV) are recommended in young children with the first dose given at different times depending on the setting. In low-incidence settings the MCV1 is given at 12 months of age or later as more infants over 12 months of age respond to MCV1 due to the absence of maternal antibody interference and an overall better immune response due to the maturation of the infant immune system. In high measles incidence settings MCV1 is given earlier at 9 months of age as there is no remaining protection from maternal antibody at this age and risk of infection if unvaccinated can be high. However, in children born with low levels or rapid decay of maternal antibody, the 9-month timing for MCV1 means the infant may be susceptible to infection for some months prior to vaccination. Therefore, in settings of high infant measles incidence, an early first dose at 6 months of age may bridge this susceptibility gap.

Our study will assess differences in protective levels of measles antibody in children randomised to receive early (6 months) or standard (9 months) MCV1 in a high incidence measles setting, and early (12 months) or standard (18 months) booster vaccines, in those who are given early MCV1. There will be 5 blood draws over 2 years. The study will compare children who received a) two doses of measles vaccine at 6 and 18 months with 9 and 18 months, and b) two doses of measles vaccine at 6 and 12 months compared with 6 and 18 months.

The study is funded by the Bill \& Melinda Gates Foundation (INV-048650)

Eligibility criteria: 1. Trial Participants Children aged 6 months (23 - 28 weeks) at time of screening
2. Inclusion Criteria

   * Aged 6 months (23 - 28 weeks) at time of screening
   * Received all previous vaccines as per country Expanded Programme of Immunization (EPI) schedule, verified by child health card
   * Parents/caretakers willing to give informed consent for their and their children's participation and stay in the geographical area where the study would be conducted
3. Exclusion Criteria

The participant may not enter the trial if any of the following apply:

* Child not healthy enough to be vaccinated in the opinion of the investigator
* Recent family history of measles infection (since birth)
* Previous receipt of any measles vaccination
* A family history of congenital or hereditary immunodeficiency other than HIV
* Receipt of more than 1 week of immunosuppressant or immune modifying drugs e.g. high dose steroids.
* Major congenital defects or serious chronic illness that in the opinion of the investigator are likely to modify immune responses or the ability to comply with the requirements of the study.
* History of any neurological disorders or seizures
* Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period
* Other abnormalities or medical history that contraindicated measles vaccination

Primary outcomes:
measure: Protective measles antibody concentrations at 2.5 years of age
timeFrame: 2.5 years of age
measure: Local and systemic reactions
timeFrame: 7 days post each vaccination
measure: Serious Adverse Events
timeFrame: 2 years: (from baseline vaccination until 2 year follow up visit)
Secondary outcomes:
measure: Measles plaque reduction neutralisation titre (PRNT) and immunoglobulin G (IgG) concentration
timeFrame: one month after first dose
measure: The effect of maternal human immunodeficiency virus (HIV) infection
timeFrame: one month after first dose and second dose
measure: The effect of maternal antibodies on infant immune response
timeFrame: pre-vaccination, 4 weeks after the first dose, 4 weeks after the second dose
measure: Immune response to rubella component of the vaccine
timeFrame: 4 weeks after a first and second dose
Other outcomes:
measure: Public perceptions of measles immunisation
timeFrame: Baseline until 2 year follow up visit
Locations:
city: Kampala
country: Uganda
facility: Makarere University - Johns Hopkins University Collaboration
Study officials:
References: