A Phase II Randomized, Observer-blind Controlled Pilot Study to Compare the Safety and Immunogenicity of Acellular Pertussis Vaccines Including Chemically or Genetically-detoxified Pertussis Toxin in Adolescents Aged 11-15 Years Previously Immunized With Acellular Pertussis Vaccines
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Geometric mean concentration (GMC) of neutralizing antibodies to PT
研究概览
简要总结
This is a phase II, randomized double-center, and observer-blind controlled pilot vaccine trial in 11 to 15 years old healthy subjects to assess the immunogenicity of the genetically detoxified pertussis toxin (rPT) included in a novel acellular pertussis vaccine (Pertagen®) manufactured by BioNet-Asia when delivered by the intramuscular route to adolescents previously primed and boosted with chemically-detoxified PT, along with Td-pur® and in comparison with that of Boostrix® dTpa.
At Day 0, eligible volunteers will undergo a venous bleed for the determination of baseline values and enter the randomization scheme, being allocated to one of two groups: A (Pertagen® + Td-pur®), B (Boostrix® dTpa).
Randomized participants will receive one dose of Pertagen® and Td-pur® (Group A) or 1 dose of Boostrix® dTpa (Group B) by intramuscular injection in the deltoid. All subjects will be observed in the Plateforme de Recherché Pédiatrique for 30 minutes after immunization.
Post-immunization local and systemic reactions will be followed up for 7 days after immunization. Adverse events will be followed for 28 days after immunization.
At Day 28, a second visit (study end visit) will take place for safety evaluation and blood draw for immunogenicity evaluation.
Blood draws performed on Day 0 (Baseline) and Day 28 will be used to evaluate immune response to study vaccines.
The primary statistical analysis will be performed with visit 2 (Day 28) data to compare the immunogenicity and safety of one dose of Pertagen®, given simultaneously with Td-pur®, to those elicited by Boostrix® dTpa.
详细描述
A significant increase of pertussis incidence is reported in a growing number of countries. This resurgence is considered as resulting from the limited durability of aP-vaccine-induced immunity and is associated with increased mortality in young infants and morbidity at all age groups. As the pertussis immunity acquired through immunization or infection is short-lived, its maintenance or reactivation requires repeat boosting at regular time points. Thus, novel strategies capable of reactivating pertussis immunity in older children, adolescents or adults, including pregnant women, are needed.
A puzzling observation is that the efficacy of current acellular pertussis vaccines (which contain chemically-detoxified pertussis toxoid (PT)) is higher in infants and children than adolescents, in whom vaccine efficacy is limited and rapidly wanes. This may derive - at least in part - from priming and repeat immunizations with acellular vaccines containing chemically-detoxified PT and thus induction of antibodies specific of the chemically-detoxified PT but unable to efficiently recognize the native PT expressed by B. pertussis.
The development of optimized acellular pertussis vaccines should thus include antigens with a similar immunogenicity profile as native PT but deprived of its toxic properties. This is best achieved through the genetic rather than chemical detoxification of PT, which results in both nontoxic and immunogenic PT.
Clinical studies have shown the good tolerability profile and the superior immunogenicity profile of acellular pertussis vaccines including genetically-detoxified PT (rPT) in adults and adolescents previously primed with whole-cell pertussis (wP) vaccines. As whole-cell vaccines express native PT, whether the superior immunogenicity of rPT will be observed in adolescents/adults previously primed with acellular pertussis vaccines containing chemically-detoxified PT is of key importance.
This is a phase II randomized, observer-blind controlled study to compare the safety and immunogenicity of acellular pertussis vaccines including chemically or genetically-detoxified pertussis toxin in adolescents aged 11-15 years. The primary objective is to assess the immunogenicity of the genetically detoxified pertussis toxin (rPT) included in a novel acellular pertussis vaccine (Pertagen®) when delivered by the intramuscular route to adolescents previously primed and boosted with chemically-detoxified PT, along with Td-pur® and in comparison with that of Boostrix® dTpa. The secondary objectives are (1) to assess safety of Pertagen® when administered with Td-pur® to adolescents as compared to Boostrix® dTpa and (2) to assess the humoral responses elicited by Pertagen® when administered with Td-pur® as compared to Boostrix® dTpa.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 11 Years 至 15 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Geometric mean concentration (GMC) of neutralizing antibodies to PT
时间窗: At 28 days after vaccination
次要结局
- Safety endpoints evaluated by solicited local and systemic reactions and unsolicited adverse events (AEs)(Solicited local and systemic reactions will be followed up for 7 days and AEs for 28 days after vaccination)
- GMCs and seroresponse rates of PT, FHA, tetanus and diphtheria-toxoid specific IgG antibodies measured by ELISA(At 28 days after vaccination)
- Seroresponse rates of PT specific neutralizing antibodies Time Frame: At 28 days after vaccination(At 28 days after vaccination)
- Reverse cumulative distribution curves of PT neutralizing antibodies, and of PT, FHA, tetanus and diphtheria-toxoid IgG antibodies(At 28 days after vaccination)
研究者
Siegrist Claire-Anne
Director of Center for Vaccinology
University Hospital, Geneva