Immunogenicity of Fractional One-fifth and One-half Doses of Yellow Fever Vaccine Compared to Full Dose in Children 9-23 Months Old
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 1,788
- 试验地点
- 1
- 主要终点
- Immune response at 4 weeks in terms of seroconversion following vaccination
研究概览
简要总结
A randomized clinical trial comparing fractional dose Yellow Fever vaccination to the full dose among children aged 9-23 months in Uganda. Children will have immune response assessed at baseline, 4 weeks, and 12 months after vaccination.
Enrolled participants will be randomized to one of three arms:
A. One-fifth fractional dose (0.1 ml) administered subcutaneously B. One-half fractional dose (0.25 ml) administered subcutaneously C. Full dose (0.5 ml) administered subcutaneously
详细描述
Yellow fever (YF) is a potentially fatal disease causing some 29,000 - 60,000 deaths in Africa alone in 2013. Vaccination with the YF vaccine is the most effective way of preventing YF and a single full dose of vaccine provides life-long protection. Indeed, over half a billion doses of the YF vaccine have been successfully used worldwide since its introduction over 80 years ago in the 1930s, including in children <2 years of age. The World Health Organization (WHO) recommends that YF vaccine be administered to all people ≥ 9 months of age. It should be noted that four YF vaccines are prequalified for use by WHO. Between 2007 and 2016, more than 105 million people have been vaccinated against YF in 14 African countries, including millions of children 9-24 months of age. Each year 6 million doses of YF vaccine are placed into an emergency stockpile to assist in the rapid response and control of outbreaks. During 2016, large outbreaks of YF in Angola and the Democratic Republic of Congo (DRC) depleted the stockpile multiple times and led to critical shortages in YF vaccine. Given the acute vaccine shortage, the World Health Organization (WHO) reviewed available data and determined that the use of fractional dose YF vaccination was a safe and effective option for mass vaccination to control outbreaks. Fractional 1/5th dose of YF vaccine manufactured by BioManguinhos, 17DD, was then used in a campaign targeting 8 million people in DRC's capital city of Kinshasa. However, only persons aged 2 years of age and older were given the fractional dose as there were no data regarding its use in children. To optimize vaccination coverage and vaccine use in outbreak responses, studies of fractional dose YF vaccine effectiveness in children less than 2 years of age were assessed as a research priority by the Strategic Advisory Group of Experts on Immunization (SAGE).
To address this critical information need, the investigators will conduct a randomized clinical trial comparing fractional dose 17DD YF vaccination to the full dose among children aged 9-23 months in Uganda. Exclusion criteria will include children who have previously received YF vaccine or who have contraindications or precautions to YF vaccination.
Enrolled participants will be randomized to one of three arms:
A. One-fifth fractional dose (0.1 ml) administered subcutaneously B. One-half fractional dose (0.25 ml) administered subcutaneously C. Full dose (0.5 ml) administered subcutaneously
The one-fifth and one-half doses of YF vaccine were both recommended for further research by WHO and YF vaccine experts.
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
- None
入排标准
- 年龄范围
- 9 Months 至 23 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age 9 to 23 months at the time of enrollment
- •Intent to stay in the health center catchment area and availability to do study visits at 2 weeks, 4 weeks, and 12 months after enrollment date
- •Informed consent signed by parent/guardian for child's participation in the study, including blood sample collections at 4 week and 12 month visits post-vaccination
- •Willingness of parent/guardian to be contacted by study personnel by telephone and through home visits if they cannot be reached by telephone.
排除标准
- •Verbal or written report of previous vaccination against YF
- •Verbal or documented history of YF disease
- •Contraindication for YF vaccine including:
- •Allergy to eggs, gelatin, or neomycin
- •Severe immune deficiency immunological including symptomatic HIV infection and HIV- infected persons with CD4 T-cell counts ≤200 cells/ mm³, primary immunodeficiencies, having received immunosuppressive doses of oral or injectable corticosteroids (or equivalent), having received immunomodulatory or chemotherapeutic agents
- •Thymus disorder
- •History of malignant neoplasm or recent hematopoietic stem cell transplantation
- •Serious illness/fever (mild illness without fever is not an exclusion criterion)
- •Administration of immunoglobulins or other blood derivative within 6 months of enrollment in the study or during the study
- •a. Exception: children with a history of Kawasaki disease who received gammaglobulin cannot be enrolled if they received it in the previous 11 months.
- •Administration of any other attenuated viral vaccine in the month prior to enrollment, or if the administration of any other attenuated viral vaccine is expected during the month after enrollment. Note: the administration of measles vaccine on the same day as YF vaccination is not a contraindication; however, if Uganda introduces measles-rubella vaccine (MR), participants will not be able to receive MR on the same day as YF vaccine due to possible interference between rubella and YF vaccine. In this situation, children will have to delay study enrollment until 1 month after MR vaccination.
- •Participating in another clinical drug trial of a drug, vaccine, or medical device
- •Severely underweight defined as ≤ 3rd percentile in the height/weight tables
- •Severe reaction to prior vaccination
- •Any chronic or other condition that, in the opinion of the study staff, represents a health risk to the participant or interferes with the evaluation of the response to the vaccine
研究组 & 干预措施
One-fifth fractional dose
One-fifth fractional dose (0.1 ml) of Yellow Fever 17DD Vaccine administered subcutaneously
干预措施: Yellow Fever 17DD Vaccine (Biological)
One-half fractional dose
One-half fractional dose (0.25 ml) of Yellow Fever 17DD Vaccine administered subcutaneously
干预措施: Yellow Fever 17DD Vaccine (Biological)
Full dose
Full dose (0.5 ml) of Yellow Fever 17DD Vaccine administered subcutaneously
干预措施: Yellow Fever 17DD Vaccine (Biological)
结局指标
主要结局
Immune response at 4 weeks in terms of seroconversion following vaccination
时间窗: 4 weeks post vaccination
Assess whether seroconversion following one-fifth (0.1 ml) and one-half (0.25 ml) doses of YF 17DD vaccine is non-inferior to seroconversion following a full dose (0.5 ml) at 4 weeks post-vaccination in children aged 9 - 23 months. Study endpoints at 4 weeks will be the following: Seroconversion will be defined as seronegative participants (plaque reduction neutralization test with a 50% cut-off (PRNT50) \< 10) at enrollment who become seropositive (PRNT50 ≥ 10) at 4 week follow-up. A boosted response will be defined as baseline-positive participants who demonstrate a four-fold or greater change in YF virus-specific titers between the baseline and 4 week specimens, e.g. a change from 1:20 to 1:80.
次要结局
- Immune response at 12 months in terms of seroconversion following vaccination(12 months post vaccination)