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

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.

Study Overview

• Status: Recruiting
• Conditions: Measles
• Intervention / Treatment: Biological: Licenced Measles-Rubella vaccine

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 Type: Interventional
• Enrollment (Estimated): 450
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Oxford Vaccine Group; Phone Number: 01865 611400; Email: info@ovg.ox.ac.uk

Study Locations

• Uganda
  • Kampala, Uganda
    • Recruiting
    • Makarere University - Johns Hopkins University Collaboration
    • Contact: Kirsty Le Doare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: 6 and 12 months; Early Prime-Boost schedule: Measles vaccines given at 6 and 12 months of age	Biological: Licenced Measles-Rubella vaccine; Licenced Measles-Rubella vaccine provided by the Ugandan EPI programme
Experimental: Group B: 9 and 18 months (standard schedule); Standard schedule: Measles vaccines given at 9 and 18 months of age	Biological: Licenced Measles-Rubella vaccine; Licenced Measles-Rubella vaccine provided by the Ugandan EPI programme
Experimental: Group C: 6 and 18 months; Early Prime schedule: Measles vaccines given at 6 and 18 months of age	Biological: Licenced Measles-Rubella vaccine; Licenced Measles-Rubella vaccine provided by the Ugandan EPI programme

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measles plaque reduction neutralisation titre (PRNT) and immunoglobulin G (IgG) concentration	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	one month after first dose
The effect of maternal human immunodeficiency virus (HIV) infection	Infant PRNT and IgG responses post MCV1 and MCV2 in children of mothers with and without HIV	one month after first dose and second dose
The effect of maternal antibodies on infant immune response	Relationship between baseline titres (pre vaccination) and 4 week post-vaccination titres for PRNT, Measles IgG, and measles ELISpot.	pre-vaccination, 4 weeks after the first dose, 4 weeks after the second dose
Immune response to rubella component of the vaccine	Anti-rubella IgG	4 weeks after a first and second dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Public perceptions of measles immunisation	Focus group interviews with the public and parents/guardians of enrolled children	Baseline until 2 year follow up visit

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: St George's, University of London; MU-JHU CARE

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2023
• Primary Completion (Estimated): May 10, 2026
• Study Completion (Estimated): May 10, 2026

Study Registration Dates

• First Submitted: December 19, 2023
• First Submitted That Met QC Criteria: October 29, 2024
• First Posted (Actual): October 31, 2024

Study Record Updates

• Last Update Posted (Actual): October 31, 2024
• Last Update Submitted That Met QC Criteria: October 29, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: measles-rubella vaccine
• Additional Relevant MeSH Terms: Infections; RNA Virus Infections; Virus Diseases; Paramyxoviridae Infections; Mononegavirales Infections; Morbillivirus Infections; Measles
• Other Study ID Numbers: OVG2022/06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No