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.
Condition: Measles; Mumps; Rubella; Varicella
MeSH terms: Measles; Rubella; Mumps
Study type: Interventional
Phase: Phase 3

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).

      Returns for blood sampling will be scheduled for 51 days, ranging from 42 to 60 days after
      dose of MMR vaccine dose and after tetraviral. We will colect the firt blood sample before
      the first vaccination too.

      It will describe the major adverse events observed after vaccination , comparing their
      frequency in groups of MMR vaccine with the Brazilian reference vaccine .
    

Detailed description: 
      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 monitoring visits.

      Plan for data analysis

      The consistency of production batches (equivalence) .Upper and lower limits of the confidence
      intervals of 95% of the difference in seroprotection results for each of the three pairs of
      contrasting antigens lots (three batches compared in pairs) between -10% and +10%, two-tailed
      analysis.

      . ratio of the geometric mean titers for each of the antigens between 0.5 and 2. The 3 lots
      will be considered to be consistent in terms of TMG to a particular vaccine component, if all
      three 95% CI of the ratio of two-tailed paired TMG are between 0.5 and 2.

      Non-inferiority

        -  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. .)

        -  ratio of the geometric mean titers for each of the antigens ≥ 0.5 (for vaccines and
           vaccine Bio-Manguinhos reference).

      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.
    

Intervention name(s): MMR Bio-Manguinhos; MMR GlaxoSmithKline
Intervention type(s): Biological; Biological
Intervention description(s): 1170 children will receive 100% produced by Bio-Manguinhos, 3 diferents lots. Application of a 0.5 ml dose, subcutaneous 390 children will receive 0,5 ml, subcutaneous, MMR GlaxoSmithKline; 390 children will receive 0,5 ml MMR GlaxoSmithKline
Other intervention name(s): MMR GlaxoSmithKline; MMR Bio-Manguinhos
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Health Services Research
Keywords: Measles, mumps and rubella vaccine; Tetraviral vaccine; Immunogenicity, Reactogenicity and Safety; Consistency of production