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.

NCT01991899 | Completed Phase 3 DMC

• 1 other identifier: ASCLIN/002/2013
• Study Type: interventional
• Target: 1,560
• Locations: 1 country
• Sites: 1

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. 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).
2. 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).

Conditions

Measles; Mumps; Rubella; Varicella

Keywords

Measles, mumps and rubella vaccine; Tetraviral vaccine; Immunogenicity, Reactogenicity and Safety; Consistency of production

Outcome Measures

Primary Outcomes (3)

• Immunogenicity comparing the 3 lots of MMR vaccine produced totally in Brazil and reference 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.

  Thirty days after MMR vaccine

• Safety

  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-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.

  Thirty days after MMR vaccine

• Determine the consistency of production

  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.

  Thirty days after MMR vaccine

Secondary Outcomes (2)

• Adverse events after tetraviral

  Three months after MMR vaccine

• Seroconversion after vaccine tetraviral( measles, mumps,rubella and varicela)

  Four months after MMM vaccine

Study Arms (2)

MMR Bio-Manguinhos

EXPERIMENTAL

Arm 1:1170 children will receive MMR Bio-Manguinhos, 3 diferents lots

Biological: MMR Bio-Manguinhos

MMR GlaxoSmithKline

ACTIVE COMPARATOR

Arm 2:390 children will receive MMR GlaxoSmithKline

Biological: MMR GlaxoSmithKline

Interventions

MMR Bio-Manguinhos BIOLOGICAL

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

Also known as: MMR GlaxoSmithKline

MMR Bio-Manguinhos

MMR GlaxoSmithKline BIOLOGICAL

390 children will receive 0,5 ml MMR GlaxoSmithKline

Also known as: MMR Bio-Manguinhos

MMR GlaxoSmithKline

Eligibility Criteria

• Age: 12 Months - 18 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• \- 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.
• 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 .

Sponsors & Collaborators

• The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz): lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Instituto Evandro Chagas

Belém, Pará, 67030-000, Brazil

Location

MeSH Terms

Conditions

Measles; Mumps; Rubella; Chickenpox

Condition Hierarchy (Ancestors)

Morbillivirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections; Rubulavirus Infections; Parotitis; Parotid Diseases; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Rubivirus Infections; Togaviridae Infections; Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections

Study Officials

• Eliane Matos Santos

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2013
• First Posted: November 25, 2013
• Study Start: February 1, 2015
• Primary Completion: December 1, 2015
• Study Completion: July 1, 2016
• Last Updated: July 11, 2016

Record last verified: 2016-07

Locations

BR (1)