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.
Information source: The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Measles; Mumps; Rubella; Varicella
Intervention: MMR Bio-Manguinhos (Biological); MMR GlaxoSmithKline (Biological)
Phase: Phase 3
Status: Recruiting
Sponsored by: The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz) Official(s) and/or principal investigator(s): Eliane Matos Santos, Principal Investigator, Affiliation: The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)
Overall contact: Eliane Matos Santos, Phone: 38827062, Email: Ematos@bio.fiocruz.br
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 .
Clinical Details
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 in Children 15-18 Months.
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Health Services Research
Primary outcome: Immunogenicity comparing the 3 lots of MMR vaccine produced totally in Brazil and reference vaccine.Safety Determine the consistency of production
Secondary outcome: Adverse events after tetraviralSeroconversion after vaccine tetraviral( measles, mumps,rubella and varicela)
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.
Eligibility
Minimum age: 12 Months.
Maximum age: 18 Months.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Children of both sexes
- Age between 12 to 15 months .
- Child in good health , without significant past medical history personal , such as
genetic syndromes , epilepsy , diabetes , severe infections and immune dysfunctions .
- Consent of father or mother , or legal guardian of the child to participate in the
study and signing the Informed Consent Form.
- Disposition of the father or mother, or legal guardian to provide name, address,
phone and other information so you can get in touch with this, if necessary .
- The responsible person be able to understand the risks of the experimente
- The responsible person be able to understand and sign the informed consent form . If
the charge is not able to sign ( illiterate ) the IC may be signed by an impartial
witness who has followed the entire procedure .
- Availability return to collect post-vaccination - The research subjects may not be
participating in another clinical study during this study.
- Not having received injectable live virus vaccine in the last 30 days.
Exclusion Criteria:
- - Children with a history of measles, rubella and / or mumps .
- Have received MMR or tetraviral previously documented in book vaccination ( eg . :
In situations of conducting national campaign or blocking vaccination before
suspected cases ).
- Have received a blood transfusion , including immunoglobulins , less than 1year .
- Skin lesions at sites of venipuncture .
- Child subject to abnormal bleeding after injections .
- Using the last 6 months at doses of corticosteroids and other immunosuppressive
immunosuppressants.
- Fever on the day of inclusion or in the 3 days prior to the inclusion in this case
may be rescheduled for inclusion 14 days after fever subsides .
- Antibiotic use on the day of inclusion or in the last 7 days prior to inclusion - in
this case , may be rescheduled for inclusion after 14 days from the last day of
antibiotic use .
- Significant abnormality on physical examination the day of enrollment . Known
systemic hypersensitivity to neomycin or any other component of the vaccine .
- Individuals with a history of severe allergy , anaphylaxis to egg proteins .
- Have received live attenuated vaccine , as the vaccine for yellow fever in the 30
days prior to vaccination with MMR and the 2nd and 3rd collections .
Locations and Contacts
Eliane Matos Santos, Phone: 38827062, Email: Ematos@bio.fiocruz.br
Instituto Evandro Chagas, Belém, Pará 67030-000, Brazil; Recruiting Francisco Lúzio de Paula Ramos, Md, Phone: (91) 3214-2187, Email: franciscoluzio@iec.pa.gov.br
Additional Information
Starting date: February 2015
Last updated: April 13, 2015
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