A Randomised Controlled Trial Comparing Two-Dose Priming With the 10-Valent Pneumococcal Conjugate Vaccine at 6 and 10 Weeks to 6 and 14 Weeks in Nepali Children
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 304
- 试验地点
- 2
- 主要终点
- Non-inferiority (proportion of infants with serotype specific IgG ≥0•35μg/mL against pneumococcal vaccine serotypes)
研究概览
简要总结
A single centre open-label, parallel group, randomised controlled trial, recruiting healthy Nepalese infants aged 40-60 days, who present to the immunisation clinic at Patan Hospital, Kathmandu, Nepal, randomised to receive a 10-valent pneumococcal conjugate vaccine (PCV10) at either;
- 6+10 weeks and 9 months OR
- 6+14 weeks and 9 months The study will enroll 152 healthy Nepalese infants in each treatment arm (304 in total). Demographic and clinical data will be collected on an electronic case report form to allow monitoring remotely. Participants will receive the study vaccine according to their allocated treatment arm in addition to their other routine vaccines. The investigators will collect 3 blood samples for analysis of serum antibody responses to the PCV10 vaccine serotypes throughout infancy (see Table 1). The data collected will be analysed in order to determine whether the 6+10 schedule is non-inferior to the 6+14 schedule in generating immune responses against the vaccine serotypes above the ≥0•35μg/mL threshold. These data will then be used to inform decision-making around augmenting the currently recommended 6+14 schedule to a 6+10 schedule in Nepal. The investigators will collect a nasopharyngeal swab at 2 time points to look at carriage of pneumococcus over time and to assess differences between the 2 groups. This is of critical importance because much of the programmatic impact of PCV is ultimately conferred by reductions in carriage at the community level and indirect effects resulting from that nasopharyngeal (NP) protection.
详细描述
BACKGROUND AND RATIONALE Streptococcus pneumoniae is the predominant cause of bacterial pneumonia, meningitis and septicaemia in children worldwide, and disproportionately affects children from developing countries. Pneumococcal conjugate vaccines (PCVs) reduce pneumococcal disease burden by direct protection and by reducing nasopharyngeal carriage, thereby preventing transmission and inducing herd protection.
In Nepal, invasive pneumococcal disease (IPD) is responsible for a substantial disease burden in children. Surveillance conducted since 2005 at Patan Hospital, Kathmandu indicates the majority of IPD is due to serotypes 1, 5 and 14, and that the greater proportion occurs in late infancy and toddlerhood.7 Vaccine introduction began in January 2015 with PCV10. GAVI (Gavi, The Vaccine Alliance) has funded an impact assessment programme (including IPD, pneumonia, nasopharyngeal (NP) colonization and health economics), which is underway.
A randomised controlled trial conducted by investigators at Patan Hospital in collaboration with the Oxford Vaccine Group, using a 10-valent PCV, demonstrated a two-dose prime (at 6 and 14 weeks) and 9-month booster to have non-inferior immunogenicity at 18 weeks and 10 months and superior immunogenicity in early childhood (2-4 years of age) compared to a conventional three-dose priming only schedule (6, 10, and 14 weeks). This two-dose prime and boost schedule, with an 8 week interval between the priming doses, has been adopted as an acceptable schedule by the World Health Organization (WHO) and recommended in late 2014 by the Nepal Ministry of Health as a result of the study. However the WHO have also recommended the introduction of a single inactivated poliomyelitis virus vaccine at 14-weeks of age in order to mitigate the risk of outbreaks from vaccine derived serotype 2 poliomyelitis virus, to protect against serotype 2 poliomyelitis virus once countries switch to bivalent OPV (oral polio vaccine) from trivalent OPV, and to enhance immunogenicity to poliomyelitis vaccine serotypes 1 and 3. This has created a programmatic dilemma and concerns around vaccine coverage as a result of requiring three injections at the 14-week visit. Thus the Nepalese Ministry of Health, based on these concerns around public acceptance and feasibility have decided to move the second PCV10 priming dose from 14 weeks to 10 weeks of age. Given this decision it is essential to evaluate the immunogenicity of the intended schedule, comparing it to the schedule that has been shown to provide a level of immunogenicity that would predict substantial program impact on disease and colonisation. This importance is further increased given that the Nepal PCV10 impact study is currently underway and the limited data on two-dose priming schedules with a one-month interval between priming doses in other settings shows a reduction in immunogenicity.
Therefore this study will be undertaken in order to evaluate the immunogenicity of the 10-valent PCV priming at 6 and 10 weeks being implemented by the Nepal Ministry of Health, compared to priming at 6 and 14 weeks of age in healthy Nepali infants. In both groups a PCV10 booster will be given at 9 months of age.
Nepal Nepal is a low-income country in South Asia with a population of 25.8 million people and an estimated under 5 year mortality of 54/1000 live births. Access to health care varies considerably within the country, but as few as 18% of children under 5 years with pneumonia are taken to health care facilities. The capital city, Kathmandu, resides in a large valley, which in 2011 had a total population of about 1,744,240 people, with approximately 10% of these being children under 5 years of age.
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
- 6 Weeks 至 8 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or Female, aged 40-60 days at time of first study vaccination
- •Parent/ guardian of participant is willing and able to give informed consent for participation in the study.
- •In good general health as determined by:
- •medical history
- •physical examination
- •clinical judgment of the investigator
- •Participants residing in Kathmandu
- •Parents able (in the Investigators opinion) and willing to comply with all study requirements.
排除标准
- •Parent/guardian unwilling or unable to give written informed consent to participate in the study
- •Previous immunisation (excluding BCG, OPV, hepatitis B, measles or other government vaccine programme) or planned vaccination during the study period with vaccine not foreseen by this study protocol except influenza vaccine and oral polio vaccination as recommended locally.
- •Premature birth (<37 weeks gestation)
- •Previous hospital admission except where hospital stay would not compromise the study in the judgment of the investigator.
- •Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.
- •Use of any investigational or non-registered product (drug or vaccine) within 30 days preceding the vaccination, or planned use during the study period.
- •Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
结局指标
主要结局
Non-inferiority (proportion of infants with serotype specific IgG ≥0•35μg/mL against pneumococcal vaccine serotypes)
时间窗: 9 months
The proportion of infants with serotype specific IgG ≥0•35μg/mL against pneumococcal vaccine serotypes at 9 months of age.
次要结局
- Serotype GMCs geometric mean concentrations (GMCs) of PCV10 serotype specific IgG)(9 months)
- Carriage (Serotype specific pneumococcal carriage)(9 months)
- Serotype proportions (proportion of infants who have PCV10 serotype-specific IgG ≥0•35μg/mL)(9 months)
- Adverse events(9 months)