Short- and Long-Term Immunogenicity and Safety of Meningococcal Group B Vaccine in Children and Adolescents With Autoimmune Rheumatic Diseases
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 263
- 试验地点
- 2
- 主要终点
- Seroconversion Rate After Vaccination
研究概览
简要总结
The goal of this clinical trial is to evaluate the humoral immunogenicity of the meningococcal B vaccine (MenB-4C) in pediatric patients with autoimmune rheumatic diseases (ARDs), compared to age- and sex-matched non-immunosuppressed controls.
The main questions it aims to answer are:
- To assess the influence of treatment on the response to the MenB-4C vaccine in patients with ARDs;
- To evaluate the impact of the MenB-4C vaccine on disease activity in patients with ARDs;
- To evaluate the safety of the MenB-4C vaccine in pediatric patients with ARDs and controls.
- To evaluate the association between physical activity levels and immunogenicity after vaccination.
Participants will:
Receive the MenB-4C vaccine (Bexsero©), administered intramuscularly in the deltoid muscle, in a 2-dose schedule (0.5 mL each), 1 month apart.
All participants will have blood samples collected immediately before vaccination at the baseline visit (D0), then receive the first vaccine dose on the same day (D0). The second dose will be administered 4 weeks after the first dose (D28). Blood samples will be collected on D0, D28, and D56. A final sample will be collected one year after the last dose (D208) to evaluate the persistence of immune response.
At study entry and one month after each dose, patients will also be assessed for clinical and laboratory disease activity using disease-specific indices and scores.
- Juvenile Systemic lupus erythematosus (JSLE): Systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) (CBC, anti-dsDNA, complement, urinalysis, protein/creatinine ratio)
- Juvenile Idiopatic Arthritis (JIA): Juvenile Arthritis Disease Activity Score (JADAS) (ESR, CRP)
- Juvenile dermatomyositis (JDM): Manual Muscle Testing (MMT) e Childhood Myositis Assessment Scale (CMAS): (CPK, transaminases, LDH)
Researcher will also perform analysis in:
Humoral immunogenicity will be assessed using serum bactericidal activity (SBA) assay with exogenous complement (baby rabbit, Pel Freez) against four test strains: H44/76 (fHBP), 5/99 (NadA), NZ98/254 (PorA), and M10713 (NHBA), from blood samples collected at D0, D28, D56, and D208. SBA assays will be conducted at the Immunology Center of the Adolfo Lutz Institute, São Paulo. Exogenous complement will be added to serially diluted serum samples, followed by the addition of a bacterial suspension. The humoral response rate induced by the vaccine, or seroconversion, will be defined by the bactericidal titer (the dilution that results in 50% bacterial killing within 60 minutes compared to the control), with titers ≥ 1:4 considered bactericidal. The geometric mean titers will be calculated using the exponential of the mean of the log-transformed concentrations.
Immunosuppressive treatments (NSAIDs, prednisone/prednisolone, intra-articular steroids, hydroxychloroquine, methotrexate, azathioprine, leflunomide, cyclosporine, tacrolimus, mycophenolate mofetil, and biologics [anti-TNF, tocilizumab, abatacept, belimumab, rituximab]) will be recorded sistematicaly.
Physical activity levels will be assessed using validated, age-appropriate methods.
详细描述
Invasive meningococcal disease (IMD) is a severe infection caused by Neisseria meningitidis and can be life-threatening. In Brazil, the incidence of IMD has been reported as 2 per 100,000 children and adolescents, with serogroups B and C being the most prevalent. Severe infections are a major concern in patients with autoimmune rheumatic diseases (ARDs), as they are recognized as a leading cause of morbidity and mortality, accounting for up to one-third of all deaths in this population.
In this context, there are currently two licensed vaccines against serogroup B in Brazil: the MenB-4C vaccine (Bexsero©) by GlaxoSmithKline (GSK), which includes four components, and the MenB-FHbp vaccine (Trumenba©) by Pfizer, which includes two components. The MenB-4C (Bexsero©) vaccine has broader coverage and is recommended in Brazil from 2 months of age. MenB-FHbp (Trumenba©, Pfizer) is approved in Brazil only for adolescents and young adults aged 10 to 25 years. Neither of these vaccines is included in Brazil's National Immunization Program (PNI) due to their high cost.
Currently, the MenB-4C vaccine is licensed in over 35 countries and consists of three recombinant antigenic proteins. The Brazilian Society of Pediatrics recommends MenB-4C vaccination for children and adolescents aged 2 to 18 years, administered in two doses at least one month apart.
The immunogenicity and safety of MenB-4C has been demonstrated in the general population through a meta-analysis of 18 studies, including phase I, II, and III randomized controlled clinical trials, involving 6,637 children and adolescents aged 2 months to 17 years. The incidence of serious adverse events (SAEs) potentially related to the vaccine was very low (0.54%) but significantly higher than in controls (0.12%) who received routine childhood vaccines. Despite this, the safety profile of MenB-4C is considered acceptable.
Physical activity is a low-cost, scalable behavioral intervention that may enhance immune function, particularly relevant in immunocompromised populations such as children and adolescents with ARDs. While higher physical activity levels have been linked to improved vaccine responses in adults, its role in pediatric ARD patients remains unexplored. This study aims to fill this knowledge gap by investigating the association between physical activity and the humoral immune response to the MenB-4C vaccine, using both subjective and objective assessment methods.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants must be between 2 and 25 years of age with no prior history of MenB-4C vaccination.
- •Patients classified with autoimmune rheumatic diseases will be invited to participate.
- •Patients with JIA must meet the classification criteria of the International League of Associations for Rheumatology; patients with JSLE, the American College of Rheumatology criteria; and those with JDM, the Bohan & Peter criteria.
排除标准
- •History of any reaction or hypersensitivity to any vaccine component;
- •Acute infectious disease and/or fever at the time of vaccination;
- •Pregnancy or breastfeeding;
- •History of Guillain-Barré syndrome;
- •Participants who fail to attend evaluation visits and laboratory sample collection; hospitalization at study inclusion;
- •Transfusion of blood products within 6 months prior to the study;
- •Application of any vaccine within one month prior to each dose.
研究组 & 干预措施
J-ARDs
Patients with ARDs will receive 2 doses (0.5 mL each) of Bexsero, 1 month apart
干预措施: Meningococcal B (Bexsero) (Biological)
Control
Healthy participants will receive 2 doses (0.5 mL each) of Bexsero, 1 month apart
干预措施: Meningococcal B (Bexsero) (Biological)
结局指标
主要结局
Seroconversion Rate After Vaccination
时间窗: Day 28 to Day 208
Proportion of participants who achieve seroconversion. The humoral response rate induced by the vaccine, or seroconversion, will be defined by the bactericidal titer (the dilution resulting in 50% bacterial killing within 60 minutes compared to the control). Titers ≥ 1:4 will be considered bactericidal. The geometric mean titer will be calculated using the exponential of the mean of log-transformed concentrations.
次要结局
- Influence of Immunosuppressive Treatment on the response to MenB-4C vaccination(Day 28 to Day 208)
- Impact of MenB-4C vaccination on Disease Activity on patients with JIA(Day 1 through D56)
- Impact of MenB-4C vaccination on Disease Activity on patients with JSLE(Day 1 through Day 56)
- Impact of MenB-4c vaccination on Disease Activity on patients with JDM(Day 1 through Day 56)
- Number of patients with adverse events related to the vaccination with MenB-4C(Day 1 through Day 56)
- Seroconversion Rates after MenB-4C vaccination by Physical Activity Classification(Day 1 to 208 post-vaccination)
- Geometric mean titers of human serum bactericidal antibodies after the MenB-4C Vaccination by Physical Activity Classification(Day 1 to 208 post-vaccination)