Earlier Prime-BOOST Schedule to Improve MEasles Protection in High Burden Settings

Phase 2

Recruiting

• Conditions: Measles
• Interventions: Biological: Licenced Measles-Rubella vaccine

• Registration Number: NCT06667206
• Lead Sponsor: University of Oxford

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)

Study Timeline

• Study Start: 2023-11-15
• Status Verified: 2023-12
• Study First Submitted: 2023-12-19
• Study First Submitted QC: 2024-10-29
• Last Update Submitted: 2024-10-29
• Study First Posted: 2024-10-31
• Last Update Posted: 2024-10-31
• Primary Completion: 2026-05-10
• Study Completion: 2026-05-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A: 6 and 12 months	Licenced Measles-Rubella vaccine	Early Prime-Boost schedule: Measles vaccines given at 6 and 12 months of age
Group B: 9 and 18 months (standard schedule)	Licenced Measles-Rubella vaccine	Standard schedule: Measles vaccines given at 9 and 18 months of age
Group C: 6 and 18 months	Licenced Measles-Rubella vaccine	Early Prime schedule: Measles vaccines given at 6 and 18 months of age

Primary Outcome Measures

Name	Time	Method
Protective measles antibody concentrations at 2.5 years of age	2.5 years of age	Proportion of participants with protective levels of measles neutralising antibodies (PRNT\>120mIUL)
Local and systemic reactions	7 days post each vaccination	Reactogenicity profile from diary cards
Serious Adverse Events	2 years: (from baseline vaccination until 2 year follow up visit)

Secondary Outcome Measures

Name	Time	Method
Measles plaque reduction neutralisation titre (PRNT) and immunoglobulin G (IgG) concentration	one month after first dose	Measles PRNT and IgG concentrations one month after first dose in infants receiving an early (6 months) compared to standard (9 month) dose of MCV
The effect of maternal human immunodeficiency virus (HIV) infection	one month after first dose and second dose	Infant PRNT and IgG responses post MCV1 and MCV2 in children of mothers with and without HIV
The effect of maternal antibodies on infant immune response	pre-vaccination, 4 weeks after the first dose, 4 weeks after the second dose	Relationship between baseline titres (pre vaccination) and 4 week post-vaccination titres for PRNT, Measles IgG, and measles ELISpot.
Immune response to rubella component of the vaccine	4 weeks after a first and second dose	Anti-rubella IgG

Trial Locations

Locations (1)

Makarere University - Johns Hopkins University Collaboration; 🇺🇬 Kampala, Uganda