The Effect of Fractional Doses of Pneumococcal Conjugate Vaccines (PCV10 and PCV13) on Immunogenicity and Vaccine-serotype Carriage in Kenyan Infants
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 2,100
- 试验地点
- 1
- 主要终点
- Immunogenicity: The ratio of IgG GMCs at 1-month post boost
研究概览
简要总结
Before the introduction of pneumonia vaccines in 2000, between 700,000 - 1 million children died each year as a result of infection with the bacteria Streptococcus pneumoniae and the resulting diseases, namely, meningitis, sepsis and pneumonia. Most of the deaths were in Africa and Asia. Where the vaccines have been introduced, they have been highly effective and have already reduced disease. However, at 10 USD per child, they are not affordable to most low-income countries without financial support from Gavi, the Vaccine Alliance.
This project aims to assess whether lower doses of the two commercially available pneumonia vaccines can protect Kenyan infants as well as the full dose. The results could be used to increase the affordability of the pneumonia vaccine, and enable delivery of the vaccine to continue in the absence of Gavi support.
详细描述
Background:
PCV is currently the most expensive vaccine in the routine immunisation schedule in Gavi-supported countries. This study aims to provide evidence which may enable a substantial decrease in the cost of PCV programmes, therefore increasing the sustainability of PCV programmes in low and middle income countries (LMICs). We propose to assess whether fractional (20% and 40%) doses of pneumococcal conjugate vaccine (PCV10 and PCV13) in a 2p+1 schedule (2 primary doses followed by a booster dose) induce non-inferior immunogenicity and effects on vaccine-serotype carriage when compared to the full dose. These lower doses could convert new 4-dose vials of PCVs into 10- or 20-dose vials, ready for immediate implementation in LMIC programmes.
Primary objective:
Non-inferior immunogenicity at 1-month post-boost (10 months of age). Non-inferiority will be reached if the lower CI around the ratio of geometric mean concentrations (GMC) of IgG (fractional/full dose) is >0.5 (i.e. the 2-fold criterion).
Secondary objectives:
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
Participants, parents of participants and all of the study team apart from the vaccinator will be masked with respect to the infant's allocation to a trial arm between A-F. If randomly allocated to trial arm G, parents and study personnel will be unmasked due to the necessity for trial arm G to receive a different vaccine schedule compared to trial arms A-F. It is thought that this unmasking will have minimal impact on retention, follow up and outcome assessment across the trial arms for primary and secondary outcomes.
入排标准
- 年龄范围
- 6 Weeks 至 8 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy infants aged 6-8 weeks of age (HIV positive or negative but with no symptoms of current clinical immunosuppression i.e. HIV infection at WHO clinical stage 1);
- •Parents are willing to provide informed consent for their child to participate in the study
- •Parents and infant are likely to remain in the study area until the infant is 18 months of age and comply with study requirements including the requirement to return to the same health facility to obtain all other childhood vaccines.
排除标准
- •Infants >8 weeks of age at time of enrolment
- •Signs or symptoms of immunosuppression or HIV infection clinical stage 2 or above.
- •Acute illness (e.g. febrile disease) on the day of vaccination
- •Contraindications precluding vaccination (e.g. hypersensitivity to any component of the vaccine, including diphtheria toxoid)
- •Previous PCV vaccination
- •Family are planning to migrate out of the study areas before the end of the study follow-up
- •Family are planning to obtain the subsequent vaccine doses of the routine immunisation schedule elsewhere and therefore their child may receive a full dose under the routine vaccination programme.
研究组 & 干预措施
Full dose PCV13 (2p+1 schedule)
Full dose PCV13 administration in 2p+1 schedule
干预措施: PCV13 (Biological)
40% dose PCV13 (2p+1 schedule)
Fractional (40%) dose PCV13 administration in 2p+1 schedule
干预措施: PCV13 (Biological)
20% dose PCV13 (2p+1 schedule)
Fractional (20%) dose PCV13 administration in 2p+1 schedule
干预措施: PCV13 (Biological)
Full dose PCV10 (2p+1 schedule)
Full dose PCV10 administration in 2p+1 schedule
干预措施: PCV10 (Biological)
40% dose PCV10 (2p+1 schedule)
Fractional (40%) dose PCV10 administration in 2p+1 schedule
干预措施: PCV10 (Biological)
20% dose PCV10 (2p+1 schedule)
Fractional (20%) dose PCV10 administration in 2p+1 schedule
干预措施: PCV10 (Biological)
Full dose PCV10 (3p+0 schedule)
The current vaccine (PCV10) and schedule (3p+0) in use in the Kenyan routine immunisation programme as an additional comparison arm.
干预措施: PCV10 (Biological)
结局指标
主要结局
Immunogenicity: The ratio of IgG GMCs at 1-month post boost
时间窗: 4-weeks post-boost (approximately 10 months of age)
The ratio of the geometric mean concentrations of IgG after vaccination with 3 full or fractional doses of PCV
次要结局
- Opsonophagocytic activity of vaccine-induced antibody to 4 serotypes(Approximately 18 months of age)
- Immunogenicity: the proportion of children who 'seroconvert' to vaccine-serotypes after vaccination(4-weeks post-primary series (approximately 18 weeks of age))
- The proportion of children with evidence of vaccine-serotype carriage(Approximately 9 months of age)
- The direct vaccine effectiveness of full/fractional doses of PCV13 against carriage of serotypes 6A and 19A(Approximately 18 months of age)