Clinical Trial: Measles-Rubella Vaccine Immunogenicity at 6 and 9 Months of Age

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Assessing Immunogenicity of Measles-Rubella Vaccine at 6 and 9 Months of Age

Brief Summary:

This is an open-label, randomized, 2-arm clinical trial in healthy infants in Bangladesh. The primary purpose of the study is to assess the immunogenicity of measles-rubella (MR) vaccine when delivered at 6 months. In addition, the study will establish the equality of MR vaccine seroconversion administered at 9 months following administration of an earlier MR vaccine dose at 6 months of age compared to MR vaccine dose administered at 9 months without previous MR vaccination. This study will also provide additional data on safety and tolerance of MR vaccine given at 6 months, and impact of maternal antibodies on immunogenicity of MR vaccine at 6 months.

• Primary objectives:

  1. To assess immunogenicity of MR vaccine at 6 months of age
  2. To assess immunogenicity of MR vaccine at 9 months of age among children without prior measles and rubella vaccination, compared with MR vaccine immunogenicity among those who had a prior MR vaccination at 6 months of age

• Secondary objectives

  1. To assess the frequency of adverse reactions following administration of MR vaccine at 6 months
  2. To compare the immunogenicity of the MR vaccine first dose administered at 6 months vs at 9 months.
  3. To assess the proportion of mothers with undetectable, detectable and protective levels of measles and rubella antibodies
  4. To determine the extent of variation in measles antibodies in women of child bearing age in a population with a long standing m
     

     Detailed Summary:

     In countries with low levels of circulating measles virus, and lower risk for measles infection, measles containing vaccine first dose (MCV1) is recommended at 12 months of age. In countries with high risk for measles, MCV1 is recommended at 9 months. In the past decade, many countries have been experiencing measles outbreaks with a high proportion of cases among infants < 9 months of age, below the recommended age of routine MCV1.

     Recent publications suggest that this may be due to the fact that the majority of infants now are born to mothers with vaccine induced immunity to measles, and who lose maternal antibodies much earlier, by age of 4-6 months. For example, in a measles outbreak in Malawi in 2010, 14% (17,858) of the estimated 134,000 cases occurred in children 0-8 months. In 2013, in a measles outbreak in Sri Lanka approximately 34% of measles cases were in children 6-12 months of age. Furthermore, in 2013 Jordan experienced a large measles outbreak with high proportion of young infants affected (6-9 months). WHO measles outbreak response guidelines recommend vaccinating children as young as 6 months during outbreaks. As an example, in response to a measles outbreak, Sri Lanka and Jordan conducted ORI that included infants 6 months of age despite the limited evidence on immunogenicity of MR vaccine at that age.

     Some researchers suggest that routine MCV should be given before age of 9 months based on published data showing that infants born to mothers with vaccine induced measles immunity are born with lower concentration of maternal measles antibodies (MMA) and lose protection against measles infection at an earlier age. Measles vaccine immunogenicity depends on several factors, including presence of maternal measles antibodies (i.e., passively acquired measles antibodies may neutralize vaccine virus before a c
     Sponsor: Centers for Disease Control and Prevention
     

     Current Primary Outcome:

     • Seroconversion at 6 months [ Time Frame: Change in antibody titers at 9 months compared to 6 months of age ]
       Measles neutralizing antibody titers (measured by plaque reduction neutralization test) and rubella titers (IU/mL) (measured by ELISA) on sera collected at 9 months of age. Seroprotection is defined as antibody level of ≥ 120 mIU/mL for measles and >10IU/mL for rubella.
     • Seroconversion at 9 months [ Time Frame: At 11 months of age. ]
       To assess immunogenicity of MR vaccine at 9 months of age among children without prior measles and rubella vaccination, compared with MR vaccine immunogenicity among those who had a prior MR vaccination at 6 months of age
     
     
     

     Original Primary Outcome: Same as current
     
     

     Current Secondary Outcome:

     • Adverse Effects Following Immunization (AEFI) [ Time Frame: Day 1 to Day 84 ]
       To assess the frequency of adverse reactions following administration of MR vaccine at 6 months
     • Immunogenicity at 9 months [ Time Frame: At 9 months and 11 months of age ]
       To compare the immunogenicity of the MR vaccine first dose administered at 6 months vs at 9 months
     • Measles and rubella titers of enrolled mothers [ Time Frame: At day 1 ]
       To assess the proportion of mothers with undetectable, detectable and protective levels of measles and rubella antibodies
     • Correlation of mothers' measles and rubella antibody levels with infants' maternal antibodies [ Time Frame: Time from randomization to 9 and 11 months ]
       To assess the correlation between measles and rubella antibody levels in women and levels of maternal antibodies in infants
     • Half-life and decay of maternal measles and rubella antibodies. [ Time Frame: Day 1 to day 84 ]
       To estimate the half-life of decay of maternal measles and rubella antibodies in infants
     
     
     

     Original Secondary Outcome: Same as current
     
     Information By: Centers for Disease Control and Prevention
     

     Dates:
     Date Received: February 21, 2017
     Date Started: March 9, 2017
     Date Completion: October 27, 2017
     Last Updated: March 1, 2017
     Last Verified: March 2017