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

Immunogenicity of Co-administered Yellow Fever and Measles, Mumps, and Rubella (MMR) Vaccines in Children Under 2 Years Old in Argentina

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.

Study Overview

• Status: Completed
• Conditions: Vaccine Response Impaired
• Intervention / Treatment: Biological: Co-administration of MMR/YF; Biological: MMR followed by YF; Biological: YF followed by MMR

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 Type: Interventional
• Enrollment (Actual): 851
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Misiones
    • Eldorado, Misiones, Argentina
      • SAMIC Eldorado Hospital
    • Obera, Misiones, Argentina
      • SAMIC Obera Hospital
    • Posadas, Misiones, Argentina
      • Favoloro Hospital
    • Posadas, Misiones, Argentina
      • IPS Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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: Co-administration of MMR/YF; Participants randomized to this arm will receive both MMR and yellow fever vaccines on Day 0.	Biological: Co-administration of MMR/YF; Both MMR & yellow fever vaccines administered on Day 0.
Active Comparator: MMR followed by YF; Participants randomized to this arm will receive MMR vaccine on Day 0 followed by yellow fever vaccine on Day 28.	Biological: MMR followed by YF; MMR vaccine administered on Day 0 and yellow fever vaccine administered on Day 28.
Active Comparator: YF followed by MMR; Participants randomized to this arm will receive YF vaccine on Day 0 followed by MMR vaccine on Day 28.	Biological: YF followed by MMR; Yellow fever vaccine administered on Day 0 and MMR vaccine administered on Day 28.

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Alba Maria Ropero
• Collaborators: Centers for Disease Control and Prevention; Ministry of Public Health, Argentina
• Investigators: Principal Investigator: Cristian Biscayart, MD, Minsterio de Salud de la Nacion, Argentina

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2015
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 30, 2018

Study Registration Dates

• First Submitted: November 21, 2017
• First Submitted That Met QC Criteria: December 7, 2017
• First Posted (Actual): December 11, 2017

Study Record Updates

• Last Update Posted (Actual): May 21, 2019
• Last Update Submitted That Met QC Criteria: May 17, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: immunogenicity; yellow fever vaccine; MMR vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Togaviridae Infections; Rubivirus Infections; Yellow Fever; Rubella
• Other Study ID Numbers: PAHO-2014-07-0011

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No