Efficacy and Safety of Dengue Vaccine in Healthy Children Aged 4 to 11 Years in Thailand
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 4,002
- 试验地点
- 1
- 主要终点
- Number of Symptomatic Virologically-Confirmed Dengue (VCD) Cases During the Active Phase Post-dose 3 Following Inj. With Either CYD Dengue Vaccine or a Placebo
研究概览
简要总结
The primary objective of the study was to assess the efficacy of CYD dengue vaccine after three injections in preventing symptomatic virologically-confirmed dengue (VCD) cases, regardless of the severity, due to any of the four serotypes in children aged 4 to 11 years at the time of inclusion.
Secondary objectives included to assess:
- Vaccine efficacy against severe VCD cases
- Vaccine efficacy against VCD cases following at least two injections with CYD dengue vaccine
- Immune response to CYD dengue vaccine
- Safety profile of CYD dengue vaccine. Safety assessments include solicited reactions within 7 or 14 days after each injection, unsolicited adverse events within 28 days after each injection, and serious adverse events during the study period.
Other objectives included:
- Vaccine efficacy against VCD cases following at least one injection with CYD dengue vaccine
- Vaccine efficacy against VCD cases due to each serotype
- Participants with clinical signs and symptoms for VCD
详细描述
Participants (both cohort 1 and 2) received 3 injections of CYD dengue vaccine. Participants (Cohort 1) received rabies vaccine at Month 0 and placebo at 6 and 12 months. Participants (cohort 2) received placebo at 0, 6, and 12 months.
Dengue cases were collected for assessment of efficacy during the Active Phase from first injection until at least 13 months after the third injection. A subset of participants were also evaluated for reactogenicity and immunogenicity.
Symptomatic VCD cases were defined as acute febrile illness with fever lasting for at least 1 day (temperature >= 37.5°C measured at least twice with an interval of at least 4 hours), confirmed by reverse transcriptase-polymerase chain reaction and/or dengue non-structural protein 1 (NS1) enzyme-linked immunosorbent assay antigen test, and occurring >28 days after the third injection.
Dengue hemorrhagic fever (DHF) Grade I, II, III, and IV according to the 1999 World Health Organization (WHO) definition:
Clinical Manifestations: a) Fever: acute onset, high and continuous, lasting 2 to 7 days. b) Any of the following hemorrhagic manifestations (including at least a positive tourniquet test): petechiae, purpura, ecchymosis, epistaxis, gum bleeding, and hematemesis and/or melena.
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
- Double (Participant, Investigator)
盲法说明
The observer-blind design was chosen since the products have different appearances and could be recognized. The person who performed vaccinations knew which product was administered while neither the participant nor the Investigator in charge of safety evaluation knew which product was injected. To maintain the blind and minimize the potential bias, the control group used the same route and schedule as the study vaccine.
入排标准
- 年龄范围
- 4 Years 至 11 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged 4 to 11 years on the day of inclusion.
- •Participant in good health, based on medical history and physical examination.
- •Provision of assent form signed by the participants (for participants >= 7 years old) and informed consent form signed by the parent or another legally acceptable representative.
- •Participant and parent/ legally acceptable representative able to attend all scheduled visits and to comply with all trial procedures.
- •Participant attended one of the schools involved in the trial and living in the Ratchaburi Province.
- •For a female participant of child-bearing potential (girls post-menarche), avoid becoming pregnant (use of an effective method of contraception or abstinence) for at least 4 weeks prior to first vaccination, until at least 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 vaccination, according to Investigator judgment.
- •For a female participant of child-bearing potential (girls post-menarche), known pregnancy or positive urine pregnancy test on the day of the first trial vaccination.
- •Personal or family history of thymic pathology (thymoma), thymectomy, or myasthenia.
- •Planned participation in another clinical trial during the present trial period.
- •Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy, or long-term systemic corticosteroids therapy.
- •Known systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to the trial vaccines or to a vaccine containing any of the same substances.
- •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.
- •Participant deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent.
- •Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination.
- •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.e
- •Participant who plans to attend another school (outside the trial area) or move to another city in the coming 30 months.
研究组 & 干预措施
Control Group
Participants (Cohort 1) received rabies vaccine at Month 0 and placebo at 6 and 12 months. Participants (Cohort 2) received placebo at 0, 6, and 12 months.
干预措施: Inactivated rabies virus vaccine (Biological)
Control Group
Participants (Cohort 1) received rabies vaccine at Month 0 and placebo at 6 and 12 months. Participants (Cohort 2) received placebo at 0, 6, and 12 months.
干预措施: Placebo (Biological)
CYD Dengue Vaccine Group
Participants (both Cohort 1 and 2) received 3 injections of the CYD Dengue vaccine, 1 injection each at 0, 6, and 12 months.
干预措施: CYD Dengue Vaccine (Biological)
结局指标
主要结局
Number of Symptomatic Virologically-Confirmed Dengue (VCD) Cases During the Active Phase Post-dose 3 Following Inj. With Either CYD Dengue Vaccine or a Placebo
时间窗: 28 days Post-Inj. 3 up to the end of Active Phase (up to 13 months Post-Inj. 3, i.e. up to 25 months)
Symptomatic VCD cases were defined as acute febrile illness with fever lasting for at least 1 day (temperature \>= 37.5 degree Celsius (°C) measured at least twice with an interval of at least 4 hours), confirmed by reverse transcriptase-polymerase chain reaction and/or dengue non-structural protein-1 (NS1) enzyme-linked immunosorbent assay antigen test, and occurring more than 28 days after the third injection. Vaccine efficacy was reported as density incidence (cases/100 person-years at risk). Density incidence was defined as the number of VCD cases divided by the cumulative person-years at risk.
次要结局
- Number of Symptomatic VCD Cases During the Active Phase Following at Least Two Inj. With Either CYD Dengue Vaccine or a Placebo(28 days Post-Inj. 2 up to Inj. 3, 28 days Post-Inj. 2 up to end of Active Phase ( up to 25 months))
- Number of Severe VCD Cases During the Active Phase Post-dose 3 Following Inj. With Either CYD Dengue Vaccine or a Placebo(28 days Post-Inj. 3 up to the end of Active Phase (up to 13 months Post-Inj. 3, i.e. up to 25 months))
- Percentage of Participants With Solicited Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo(14 days post-any Inj. and each of the 3 Inj.)
- Percentage of Participants With Solicited Inj. Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo(7 days post-any Inj. and each of the 3 Inj.)
- Geometric Mean Titers (GMTs) of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Inj. With Either CYD Dengue Vaccine or a Placebo(Pre-Inj. 1, 2, and 3, 28 days Post-Inj. 1, 2 and 3 and 1 year Post-Inj. 3)
- GMTs of Antibodies Against Each Serotype With the Parental Dengue Virus Strain in Dengue-Immune Participants Before and Following Inj. With Either CYD Dengue Vaccine or a Placebo(Pre-Inj. 1, 2, and 3, 28 days Post-Inj. 1, 2 and 3 and 1 year Post-Inj. 3)
- GMTs of Antibodies Against Each Serotype With the Parental Dengue Virus Strain in Dengue Non-Immune Participants Before and Following Inj. With Either CYD Dengue Vaccine or a Placebo(Pre-Inj. 1, 2, and 3, 28 days Post-Inj. 1, 2 and 3 and 1 year Post-Inj. 3)