Clinical Trial: Study of Immunogenicity, Reactogenicity and Safety of the Combined Measles, Mumps and Rubella Vaccine Produced by Bio-Manguinhos/Fiocruz in Children 12-15 Months of Age, Followed by Tetraviral Vaccine in Children 15-18 Months.

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Study of Immunogenicity, Reactogenicity and Safety of the Combined Measles, Mumps and Rubella Vaccine Produced by Bio-Manguinhos/Fiocruz in Children 12-15 Months of Age, Followed by Tetraviral Vaccine

Brief Summary:

It is a clinicaltrial Phase III , randomized, double -blind , 4-arm (390 each one):

This study will include 1560 children and will use 3 batches of vaccine produced by Bio - Manguinhos with viral bulk of GSK combined measles , mumps and rubella applied in healthy children 12-15 months of age, and 01 batch of MMR to reference( GSK ), applied in healthy children aged 12-15 months old . The vaccine is administered as MMR 1st dose.

Two hypotheses are tested :

  1. Consistency of production ( equivalence between batches )of 3 batches of vacines(TV1, TV2 , TV3 Bio- Manguinhos). Noninferiority vaccine Bio TV (Fiocruz, Rio de Janeiro), ie, the measles, mumps and rubella in Brazil is as immunogenic and safe as the measles, mumps and rubella reference, already used in routine NIP (production Bio-Manguinhos/FIOCRUZ with viral concentrate, bulk, GSK).

    The MMR vaccine (Bio-TV) will have the same composition (vaccine strains) and the same method of production of MMR (TV-GSK): Wistar RA27 / 3 rubella, Schwarz strain of measles vaccine, and strain RIT 4385 - derived from the Jeryl Lynn strain of mumps vaccine.

    As 2nd dose, children receive the vaccine tetraviral measles-mumps-rubella-varicella, aged 15-18 months, according to the guidance of the National Immunization Program.

  2. Noninferiority vaccine Bio TV (Fiocruz, Rio de Janeiro):the measles, mumps and rubella vaccine in Brazil is as immunogenic and safe as the measles, mumps and rubella reference, already used in routine NIP (production Bio-Manguinhos/FIOCRUZ with viral concentrate, bulk, GSK).

Status:Not yet recruiting: participants are not yet being recruited

Parents or guardians, potential participants to the study, will be identified by the field staff of the project and invited to an interview host, which will be presented in the study objectives, the necessary procedures (vaccine, blood collection and pre-vaccination postvaccination, interviews, etc..), their frequency, duration, benefits and risks of the study. It will also read and discussed the Informed Consent Form (ICF).

It will be made Serology, pre-and post-vaccination, using the technique of enzyme immunoassay (ELISA DadeBehring / SIEMENS) for measles, rubella, mumps and varicella, with titration of specific IgG antibodies in the Laboratory of Respiratory Virus / IOC / Fiocruz;

Titration of neutralizing antibodies to measles and mumps, pre and post vaccination (by Plaque Reduction Neutralization Test, PRNT) in samples that are successful seronegative. Will be held at LATEV / Bio-Manguinhos / Fiocruz.

Control of adverse events after application of vaccine will be made by means of annotations that should be completed by a responsible journal and analyzed by the doctor. They will be have a number phone 24 hours to contact with the doctor.

The monitors will visit the initiation of the study (day 0), regular visits during the study and a visit closing soon after completion of the study. Monitors should review the FRC, comparing them with source documents to verify the accuracy of data collection, assess adherence to good clinical practice and ensure that the study data are complete, accurate and integers. Monitors should make sure of the existence of time, space and qualified personnel in the days of monito
Sponsor: The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)

Current Primary Outcome:

  • Immunogenicity comparing the 3 lots of MMR vaccine produced totally in Brazil and reference vaccine. [ Time Frame: Thirty days after MMR vaccine ]

    Difference seroprotection for each of the antigens in the vaccines under test and reference vaccines or greater - 10%, one-tailed analysis. More precisely, the lower limit of 95% of the difference between the seroprotection rates in the vaccine test and reference vaccine should be greater than 10% (e.g. 4%, -3%, etc. .) evaluate the immunogenicity• Ratio of the geometric mean titers for each of the antigens ≥ 0.5 (for Bio-Manguinhos vaccine and reference vaccine).

    The analysis of non-inferiority will take into account three batches of vaccines TV1, TV2, TV3 and that will be compared together with the reference vaccine, if any consistency of production batches.

    This procedure is performed in the 2nd serology after vaccination.

  • Safety [ Time Frame: Thirty days after MMR vaccine ]
    Parents or guardians will take home the diary for recording adverse events. They will receive training on how to complete the diary of adverse events in health facilities where children are vaccinated after the first dose of MMR. They will receive a ruler and a mercury thermometer to check for adverse events and a pen for note. The diary of adverse events should be completed during the 10 days after vaccination •Adverse events will be compared for each of vaccines (TV1, TV2, TV3 and reference vaccine) and for each dose. Will determine the percentage of subjects with a report of any symptoms (solicited or unsolicited) during the 30 days of follow-

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Adverse events after tetraviral [ Time Frame: Three months after MMR vaccine ]
      Describe the major adverse events observed after vaccination.Their parents or guardians will take home the diary for recording adverse events.They will receive a ruler and a mercury thermometer to check for adverse events and a pen for note. The diary of adverse events should be completed during the 10 days after vaccination •Adverse events will be compared for each of vaccines (TV1, TV2, TV3 and reference vaccine) and for each dose. Will determine the percentage of subjects with a report of any symptoms (solicited or unsolicited) during the 30 days of follow-up after vaccination. Are tabulated the percentages of subjects with adverse events (for the overall incidence of any symptom, for the incidence of any local symptoms and the incidence of any general symptoms). The comparison between groups will be made by the chi-square test with a significance level of 0.05.requency in the vaccine groups tetraviral.
    • Seroconversion after vaccine tetraviral( measles, mumps,rubella and varicela) [ Time Frame: Four months after MMM vaccine ]
      Compare tetraviral seroconversion after MMR vaccine


    Original Secondary Outcome: Same as current

    Information By: The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)

    Dates:
    Date Received: November 8, 2013
    Date Started: February 2015
    Date Completion:
    Last Updated: July 7, 2016
    Last Verified: July 2016