Immunogenicity and Large-Scale Safety of Tetravalent Dengue Vaccine in Healthy Subjects Aged 2 to 45 Years in Singapore
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 1,198
- 试验地点
- 5
- 主要终点
- Percentage of All Participants Reporting Solicited Injection-site and Systemic Reactions Following Each Injection With CYD Dengue Vaccine or Placebo
研究概览
简要总结
Primary Objectives:
- To evaluate safety after each CYD Dengue vaccination in terms of injection site and systemic reactogenicity.
- To evaluate the occurrence of Serious Adverse Events (SAEs) throughout the trial period.
- To evaluate the humoral immune response to each CYD Dengue serotype after each vaccination in a subset of participants.
Secondary Objectives:
- To evaluate the persistence of the humoral immune response during 4 years after the last vaccination in a subset of participants.
详细描述
This was a multicenter trial involving three vaccinations one each at 0, 6 and 12 months over a period of 1 year, and a 4-year follow-up following the last vaccination.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
An observer-design for the first vaccination and a single-blind design for the second and third vaccination were chosen to minimize the bias of the vaccine evaluation. The Investigator in charge of safety evaluation, the Sponsor, and the participants/parents did not know which vaccine was administrated at the first visit. For the second and third vaccinations, the participants/parents did not know which vaccine was administered.
入排标准
- 年龄范围
- 2 Years 至 45 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged from 2 to 45 years on the day of inclusion.
- •Participant in good health, based on medical history and physical examination.
- •Provision of informed consent form (and assent form for participants aged 6 to 12 years) signed by the participant and by the parent(s) or another legally acceptable representative for participants aged less than 21 years.
- •Participants and parent(s)/legally acceptable representative able to attend all scheduled visits and comply with all trial procedures.
- •For a woman of child-bearing potential, avoid becoming pregnant (use of an effective method of contraception or abstinence) for at least 4 weeks before the first vaccination until 4 weeks after the last vaccination.
排除标准
- •Febrile illness (temperature >= 37.5°C) or moderate or severe acute illness/infection on the day of the first vaccination, according to Investigator judgment.
- •For a woman of child-bearing potential, known pregnancy or positive urine pregnancy test on the day of inclusion.
- •Breast-feeding woman.
- •Known systemic hypersensitivity to any of the components of the trial vaccines (especially egg proteins or neomycin) or history of a life-threatening reaction to the trial vaccines or to a vaccine containing any of the same substances.
- •Personal or family history of thymic pathology or myasthenia.
- •Previous hepatitis A vaccination (for children only).
- •Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the past 6 months, or long-term systemic corticosteroid therapy.
- •Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the Investigator.
- •Receipt of blood or blood-derived products in the past 3 months that might interfere with the assessment of immune response.
- •Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination.
- •Planned participation in another clinical trial during the 18 coming months.
- •Receipt of any vaccine in the 4 weeks preceding the first trial vaccination.
- •Planned receipt of any vaccine in the 4 weeks following the first trial vaccination.
- •Participant deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent.
- •Current or past alcohol abuse or drug addiction that may interfere with the participants ability to comply with trial procedures.
- •Participant who plans to move to another country within the 18 coming months.
研究组 & 干预措施
Placebo Group
All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >= 12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
干预措施: NaCl + influenza virus or hepatitis A vaccine (Biological)
CYD Dengue Vaccine Group
Participant's received the CYD Dengue Vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively.
干预措施: CYD Dengue vaccine (Biological)
结局指标
主要结局
Percentage of All Participants Reporting Solicited Injection-site and Systemic Reactions Following Each Injection With CYD Dengue Vaccine or Placebo
时间窗: Day 0 up to 14 days post-any and each injection
Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Grade 3 Solicited injection site reactions (2-11 years): Pain, incapacitating, unable to perform usual activities; Erythema and Swelling, \>=5 cm. Grade 3 Solicited injection site reactions (adolescents and adults: \>=12 years): Pain, significant; prevents daily activity; Erythema and Swelling: \>10 cm. Grade 3 Solicited systemic reactions (all participants): Fever, \>=39.0°C; Headache, Malaise, Myalgia, and Asthenia: significant; prevents daily activity.
Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Reporting Solicited Injection-site and Systemic Reactions Following Each Injection (Inj.) With CYD Dengue Vaccine or Placebo
时间窗: Day 0 up to 14 days post-each injection
Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia.
Percentage of All Participants Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After Each Vaccination With CYD Dengue Vaccine or Placebo
时间窗: Pre-Injection 1, 2, and 3 and 28 days Post-Injection 1, 2, and 3
Seropositivity against each dengue virus serotype (parental strains) was assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive participants were defined as participants with neutralizing antibody titers \>=10 (1/dilution).
Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
时间窗: Pre-Injection 1 and 28 days Post-Injection 3
Seropositivity against each dengue virus serotypes (parental strains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers \>=10 (1/dilution).
Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Who Achieved Seropositivity Against at Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
时间窗: Pre-Injection 1 and 28 days Post-Injection 3
Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes (parental strains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers \>=10 (1/dilution).
Geometric Mean Titers (GMTs) of Antibodies in All Participants Against Each Serotype With the Parental Dengue Virus Strain Before and Following Each Vaccination With CYD Dengue Vaccine or Placebo
时间窗: Pre-Injection 1, 2, and 3 and 28 days Post-Injection 1, 2, and 3
GMTs against each serotype with the parental dengue virus strains were assessed using a dengue PRNT assay.
GMTs of Antibodies by Age Groups (2-11 Years, 12-17 Years, 18-45 Years) Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine
时间窗: Pre-Injection 1 and 28 days Post-Injection 3
GMTs against each dengue virus serotype (parental strains) were assessed using a dengue PRNT assay.
次要结局
- Percentage of Participants Aged 2 to 11 Years Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo(Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years))
- Percentage of Participants Aged 12 to 17 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo(Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years))
- Percentage of Participants Aged 18 to 45 Years Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo(Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years))
- Percentage of Participants Aged 2 to 11 Years Old Who Achieved Seropositivity Against At Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo(Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years))
- GMTs of Antibodies in Participants 18 to 45 Years Old Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine or Placebo(Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years))
- Percentage of Participants (Aged 2 to 11 Years) Immune to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo(28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years))
- Percentage of Participants (Aged 2 to 11 Years) Naïve to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo(28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years))
- Percentage of Participants (Aged 12 to 17 Years) Immune to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo(28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years))
- Percentage of Participants (Aged 12 to 17 Years) Naïve to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo(28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years))
- Percentage of Participants (Aged 18 to 45 Years) Immune to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo(28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years))
- Percentage of Participants (Aged 18 to 45 Years) Naïve to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo(28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years))
- Percentage of Participants Aged 12 to 17 Years Old Who Achieved Seropositivity Against at Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo(Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years))
- Percentage of Participants Aged 18 to 45 Years Old Who Achieved Seropositivity Against at Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo(Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years))
- GMTs of Antibodies in Participants 2 to 11 Years Old Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine(Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years))
- GMTs of Antibodies in Participants 12 to 17 Years Old Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine or Placebo(Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years))