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
- 1
- 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
- •The volunteer must satisfy the following criteria to be eligible for the study:
- •Has provided written informed consent before enrollment;
- •Male or female, ages 11-15 years (inclusive) at the time of enrollment;
- •With documented history of acellular pertussis immunization (5 doses);
- •Free of clinically significant health problems, as determined by pertinent medical history and clinical examination at study screening;
- •Non-pregnant, non-lactating female :
- •for female subjects who had menarche, this implies a negative urinary pregnancy test at enrolment;
- •If sexually active, female subjects must be willing to use reliable birth control measures for 1 month after vaccination;
- •Able to attend all scheduled visits and to understand and comply with the study procedures;
排除标准
- •The volunteer may not enter the study if any of the following apply:
- •Prior dTpa immunization within the last 5 years or prior dT immunization within the last 2 years, or any other investigational vaccine likely to impact on interpretation of the trial data, as judged by the Principal Investigator;
- •Suspected or confirmed pertussis infection within the last 10 years or documented pertussis infection in a household member within the last 10 years;
- •History of severe local or systemic reactions to any vaccination or a history of severe allergic reactions;
- •Known hypersensitivity or allergy to diphtheria, tetanus, or pertussis vaccine (including excipients);
- •Receipt of investigational product up to 30 days prior to enrollment or ongoing participation in another interventional clinical trial;
- •Receipt of licensed vaccines within 30 days of planned study immunization or ongoing participation in another clinical interventional trial;
- •Acute or chronic, clinically significant psychiatric, hematologic, pulmonary, cardiovascular, or hepatic or renal functional abnormality as determined by the Investigator based on medical history, physical exam;
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection, asplenia, cytotoxic therapy in the previous 5 years, and/or diabetes;
- •Any chronic or active neurologic disorder, including seizures, and epilepsy, excluding febrile seizures as a child;
- •Has a known history of Guillain-Barré Syndrome;
- •Has an active malignancy or recent (<10 years) history of metastatic or hematologic malignancy;
- •Suspected or known alcohol and/or illicit drug abuse within the past 5 years;
- •Pregnant or lactating female, or female who intends to become pregnant during the study period;
- •Administration of immunoglobulins and/or any blood products within the 120 days preceding study entry or planned administration during the study period;
- •Receipt of chronic (>14 days) immunosuppressants or other immune modifying drugs within 6 months of study entry:
- •For corticosteroids, this will mean prednisone or equivalent ≥0.5 mg/kg/day,
- •Intranasal and topical steroids are allowed;
- •Any other significant finding that, in the opinion of the investigator, would increase the risk of the individual's having an adverse outcome by participating in this study.
- •Temporary exclusion criteria at the time of randomization
- •The following criteria constitute contraindications to administration of vaccine at that point in time; if any one of these occurs at the time scheduled for randomization, the subject may be randomized at a later date without the need for re-screening, at the discretion of the Investigator, or withdrawn at the discretion of the Investigator:
- •Acute disease at the time of randomization. (Acute disease in the context of this trial is defined as the presence of a moderate or severe illness with or without fever.) The vaccine/placebo can be administered to persons with a minor illness such as mild upper respiratory tract infection with or without low-grade febrile illness, i.e. temperature of ≤37.5°C;
- •Body temperature ≥38°C within 3 days of the intended vaccination;
- •Any other significant finding that, in the opinion of the investigator, would temporarily increase the risk of the individual's having an adverse outcome by participating in this study.
研究组 & 干预措施
Arm 1: Pertagen® aP + Td-pur®
BioNet-Asia recombinant acellular Pertussis vaccine (Pertagen®) given simultaneously with Td-pur® vaccine (Novartis/GSK) intramuscularly as a single dose on Day 0
干预措施: Pertagen® aP + Td-pur® (Biological)
Arm 2: Boostrix® dTpa
Licensed Tetanus-diphtheria (reduced dose)-acellular Pertussis vaccine (Boostrix® dTpa; GSK) given intramuscularly as a single dose on Day 0
干预措施: Boostrix® dTpa (Biological)
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