Immunogenicity of Co-administered Yellow Fever and Measles, Mumps, and Rubella (MMR) Vaccines

Phase 4

Completed

• Conditions: Vaccine Response Impaired
• Interventions: Biological: MMR followed by YF; Biological: YF followed by MMR; Biological: Co-administration of MMR/YF

• Registration Number: NCT03368495
• Lead Sponsor: Alba Maria Ropero

Brief Summary

This study evaluates seroconversion against measles, mumps, rubella and yellow fever following vaccination. One-third of children will receive both yellow fever and measles, mumps, and rubella (MMR) vaccines on the same day; one- third of children will receive MMR vaccine at enrollment followed by yellow fever vaccine 4 weeks later; one-third of children will receive yellow fever vaccine at enrollment followed by MMR vaccine 4 weeks later.

Detailed Description

The World Health Organization (WHO) and the Pan American Health Organization recommend that yellow fever and measles, mumps and rubella (MMR) vaccines be administered on the same day or at least 4 weeks apart to prevent interference between live vaccines. In 2011 a Brazilian study demonstrated lower seroconversion against yellow fever, rubella, and mumps when the two vaccines were administered on the same day compared with administering them separately. WHO urged that additional studies be conducted to examine this issue.

This Phase IV study aims to determine if seroconversion against measles, mumps, rubella, and yellow fever after administration of MMR and yellow fever vaccines on the same day is non-inferior to seroconversion after sequential administration 28 days apart in health 12-month old children.

Study Timeline

• Study Start: 2015-11-23
• Study First Submitted: 2017-11-21
• Study First Submitted QC: 2017-12-07
• Study First Posted: 2017-12-11
• Primary Completion: 2018-06
• Study Completion: 2018-06-30
• Status Verified: 2019-05
• Last Update Submitted: 2019-05-17
• Last Update Posted: 2019-05-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 851

Inclusion Criteria

• Age 12 to 24 months at the time of enrollment
• Healthy child, determined by clinical history
• Availability to do study visits and blood sampling on days 28 + 7 and 56 + 14
• Informed consent signed by parents

Exclusion Criteria

• Previous vaccination against yellow fever, measles, mumps, or rubella

• History of yellow fever, measles, mumps or rubella

• Contraindication for any of the study vaccines: yellow fever vaccine or triple viral vaccine, including:

  1. Allergy to eggs, gelatin, or neomycin
  2. Weakened immunological function, including HIV infection, primary immunodeficiencies, having received immunosuppressive doses of oral or injectable corticosteroids (or equivalent), having received immunomodulators or chemotherapeutic agents
  3. Thymus disease
  4. Serious illness/fever (mild illness without fever is not an exclusion criterion)

• Administration of immunoglobulins or other blood derivative within 6 months of enrollment in the study or during the study

  a. Exception: children with a history of Kawasaki disease who received gammaglobulin cannot be enrolled if they received it in the previous 11 months.

• Administration of any other attenuated viral vaccine (i.e., for chickenpox) in the month prior to enrollment, or if the administration of any other attenuated viral vaccine is expected during the study (up to 3 months)

• Not being available for the entire study period (up to 3 months), or not able to make the scheduled visits or complete the study procedures

• Participating in another clinical drug trial of a drug, vaccine, or medical device

• Any condition that, in opinion of the study staff, represents a health risk to the participant or interferes with the evaluation of the response to the vaccine (i.e., children in percentile ≤ 3 in the height/weight tables will be considered undernourished and cannot be selected)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MMR followed by YF	MMR followed by YF	Participants randomized to this arm will receive MMR vaccine on Day 0 followed by yellow fever vaccine on Day 28.
YF followed by MMR	YF followed by MMR	Participants randomized to this arm will receive YF vaccine on Day 0 followed by MMR vaccine on Day 28.
Co-administration of MMR/YF	Co-administration of MMR/YF	Participants randomized to this arm will receive both MMR and yellow fever vaccines on Day 0.

Primary Outcome Measures

Name	Time	Method
Seroconversion after yellow fever vaccination using the plaque reduction neutralization test (PRNT).	28-35 days post-vaccination	PRNTs will be used to measure antibody titers for yellow fever.
Seroconversion after MMR vaccination using the ELISA method.	28-35 days post-vaccination.	The ELISA method will be used to measure antibody titers for measles, mumps, and rubella.

Trial Locations

Locations (4)

SAMIC Eldorado Hospital; 🇦🇷 Eldorado, Misiones, Argentina

SAMIC Obera Hospital; 🇦🇷 Obera, Misiones, Argentina

Favoloro Hospital; 🇦🇷 Posadas, Misiones, Argentina

IPS Hospital; 🇦🇷 Posadas, Misiones, Argentina