Conjugate Vaccine Against Meningococcus C a Brazilian Project

Summary

TYPE / DESIGN STUDY: Clinical trial phase II / III, randomized, double-blind, national multi-center, with a total of 1,644 research participants stratified into 3 groups according to age for starting of the primary vaccination schedule (Stratum I - 11 to 19 years, Stratum II - 1 to 10 years; Stratum III - less than 1 year old).

BACKGROUND / STUDY CASE: Clinical trial phase II / III, which purpose is to evaluate immunogenicity, safety and reactogenicity of the vaccine against meningococcus C, conjugated to tetanus toxoid, developed by Bio-Manguinhos / FIOCRUZ (MenCC-Bio). The hypothesis of the study is that MenCC-BIO vaccine is safe and not inferior in terms of immunogenicity to the comparator vaccine currently available for the National Immunization Program in the child's immunization schedule. Thus, MenCC-Bio vaccine may meet the need for expansion of the target age group of vaccination in routine public health services and will be available to the National Immunization Program as a strategy to ensure sustainability and self-sufficiency to vaccination policy.

OBJECTIVES PRIMARY: To assess the immunogenicity of MenCC Bio-vaccine in patients from 3 months to 19 years of age, in relation to the vaccine against meningococcus C currently provided by the National Immunization Program. To evaluate the safety and reactogenicity of MenCC Bio-vaccine in patients from 3 months to 19 years old.

SECONDARY OBJECTIVES: Evaluate the cellular immune component to meningococcal C conjugate vaccine in a subset of survey participants, aged 11 to 19 years.

STUDY POPULATION: Individuals of both sexes, healthy, aged between 3 months and 19 years, attending the campus of Fiocruz / Rio de Janeiro, or municipal health units in Rio de Janeiro (living in areas covered by the municipal units health participants) that fit in the study eligibility criteria.

NUMBER OF CENTRES: Two Clinical sites.

STUDY DURATION: Estimate of 19 months.

INTERVENTION / TREATMENT: Two intervention groups (MenCC-BIO Vaccine and Comparator) in three age groups, with specific vaccination schedules. For the age groups I and II are applied 2 doses ideal interval of 6 months between them. In stratum III, are recommended 3 doses of the vaccine, at ages 3, 5 and 12 months of age, according to calendar of the National Immunization Program.

OUTCOMES PRIMARY:

Immunogenicity:

Proportion of seroconversion defined by the seronegative status change (titles of bactericidal antibodies in children rabbit complement than 1: 8) to seropositive (titers of bactericidal antibodies in larger rabbit complement or equal to 1: 8) or increase 4 times of post vaccinal compared to pre-vacianais after the full vaccination schedule by age stratum.

Geometric mean antibody titers (TGM) pre- and post-vaccination, for each vaccine group, and the ratio of these securities after the full vaccination schedule by age stratum.

Safety and reactogenicity: Frequency and intensity of adverse events solicited and unsolicited, which occurred 30 days after vaccination.

SECONDARY OUTCOME : cell detection B (CD19 +) memory phenotype (CD27 + IgD +, CD27 + IgD) in a subgroup of patients in the age stratum I (11-19 years old). ADDITIONAL INFORMATION age escalation, with interim analysis of inter-layer security and approval by the Security Independent Monitoring Committee of progression to the next lower age stratum.

Conditions

• Serogroup C Meningococcal Meningitis

Interventions

BIOLOGICAL

MenCC-BIO Vaccine

The Bio-MenCC vaccine is composed of serogroup C meningococcal polysaccharide conjugated to tetanus toxoid as the carrier protein, with 10 microgram of capsular polysaccharide of group C, 10-20 microgram of tetanus toxoid per dose and aluminum hydroxide at a concentration of 1 milligram dose (0.35 milligram Al3 +) with phosphate buffered saline as diluent. The vaccine is lyophilized and must be reconstituted with diluent and homogenized at the time of application. The lyophilised vaccine is presented as a white powder and the sterile diluent is translucent. Both are presented in vial of colorless neutral glass.

BIOLOGICAL

Combined - CRM197

The comparison is against meningococcal C vaccine produced by the Foundation Ezequiel Dias (FUNED), licensed by ANVISA and currently provided by the National Immunization Program in the child's immunization schedule. This vaccine containing 10 microgram of meningococcal C oligosaccharide conjugate 12,5-25microgram of CRM197 protein of Corynebacterium diphtheriae, and presents aluminum hydroxide (0.3 to 0.4 milligram Al3 +) in its formulation. It is also a lyophilized product must be reconstituted and homogenized before use. The meningococcal C vaccine adsorbed (combined - CRM197) comprises two frascos- ampoule, containing a white or off-white lyophilized powder and another vial containing a white opalescent suspension (diluent).

Sponsors & Collaborators

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

  lead OTHER

Principal Investigators

• Tatiana de Noronha, Doc · The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

3 Months

Max Age

19 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-09-25

Primary Completion

2019-05-31

Completion

2020-04-30

Countries

• Brazil

Study Locations