Evaluation of Different Infant Vaccination Schedules Incorporating Pneumococcal Vaccination
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 1,400
- 试验地点
- 1
- 主要终点
- proportion of children with antibody concentration ≥0.35µg/mL for individual pneumococcal serotypes
研究概览
简要总结
Pneumococcus is a group of bacteria that can cause pneumonia, meningitis and other diseases. These bacteria normally live in the nose of humans and are spread from person to person by touching or sneezing. There are vaccines available to protect against infection with these bacteria, and pneumococcus is currently the leading vaccine-preventable cause of death in young children. In countries where pneumococcal vaccine (PCV) has been introduced, there has been a big impact on the amount of disease caused by these bacteria. However, many countries, especially developing countries, are yet to introduce PCV as part of their routine immunizations. Currently a total of four doses of PCV is recommended, and the main barrier to vaccine introduction is cost. This study aims to identify a vaccination schedule to make PCV more effective and affordable for Vietnam and other developing countries.
This study has two distinct purposes: 1) to compare different dosage schedules of PCV and 2) to compare different PCV vaccines.
- Schedules of Synflorix (PCV10) involving a three, two or one dose PCV primary series and two booster options will be compared. Comparisons will be made firstly in terms of measures of immunity to the vaccine, and secondly in terms of the effect of vaccination on the carriage of bacteria in the nose.
- The responses to PCV10 and Prevenar-13 (PCV13) will be compared, in the schedule most likely to be considered for global use. Again, comparisons will be made in terms of measures of immunity and effect on carriage in the nose.
Infants aged two months will be randomly assigned to one of six study groups and will provide up to four blood samples for analysis of the measures of immunity and five nose swabs for analysis of carriage of bacteria. Infants will be followed up 8-9 times until the age of 24 months. An additional control group will be recruited at 18 months of age and also followed up until 24 months of age.
The results of this study will be used to facilitate decision making, at global and national levels, regarding introduction of PCV.
详细描述
Introduction
The overall purpose of this study is to investigate simplified childhood vaccination schedules that are more appropriate for developing country use. This study is specifically designed to address two independent questions within a single study:
- What is the optimal schedule for provision of EPI vaccines with the incorporation of PCV10? Schedules involving a three, two or one dose PCV10 primary series will be evaluated, timed around options for simplification of the Expanded Programme of Immunization (EPI) schedule for developing countries. A simplified schedule with the pneumococcal booster dose brought forward closer to the peak incidence of disease is likely both to increase compliance and vaccine effectiveness. A booster at nine months of age coincides with the usual time for administration of measles vaccine, whereas a booster at six months of age would provide earlier protection and may enable a further abbreviated 1+1 pneumococcal vaccination schedule.
- How do the responses to PCV vaccination with PCV10 or PCV13 compare? PCV10 and PCV13 are the two PCVs available through the Advanced Market Commitment (AMC) mechanism, a mechanism that provides funds for vaccine introduction into developing countries. However, there have been no studies to date directly comparing these two vaccines. Directly comparing these two vaccines will provide useful information to countries considering introduction of PCV. There are important differences between these vaccines. PCV10 includes ten pneumococcal serotypes and PCV13 includes thirteen. PCV10 uses a non-typeable Haemophilus influenzae (NTHi) Protein D carrier, which may confer protection against H. influenzae, and PCV13 uses a CRM197 carrier. It is of interest to know whether these vaccines differ either in their immunogenicity or their impact on nasopharyngeal (NP) carriage.
Design
Infants will be randomized to one of six study arms (A-F). All infant participants receive four doses of Infanrix-hexa (DTaP-Hib-HBV-IPV) and at least two doses of PCV. The PCV schedules to be evaluated are: a 3+1 PCV10 schedule at 2, 3, 4 and 9 months of age (Arm A); a 3+0 PCV10 schedule at 2, 3 and 4 months of age (Arm B); a 2+1 PCV10 schedule at 2, 4 and 9 months of age (Arm C); a 1+1 PCV10 schedule at 2 and 6 months of age (Arm D); a 2+1 PCV13 schedule at 2, 4 and 9 months of age (Arm E). Arm F, the control group, receives two doses of PCV10 at 18 and 24 months of age. An additional control group (Arm G) will be recruited at 18 months of age and will receive Infanrix-hexa at 18 months of age and a single dose of PCV10 at 24 months of age. Reactogenicity will be assessed following all vaccination visits through the use of diary cards.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 60 Days 至 74 Days（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged between 2 months and 2 months plus 2 weeks (Arms A-F) or aged between 18 months and 18 months plus 2 weeks (Arm G)
- •No significant maternal or perinatal history
- •Born at or after 36 weeks gestation
- •Written and signed informed consent from parent/legal guardian
- •Lives within approximately 30 minutes of the commune health centre
- •Family anticipates living in the study area for the next 22 months (Arms A-F) or 6 months (Arm G)
- •Has received three doses of either Infanrix-hexa or Quinvaxem in infancy (Arm G)
排除标准
- •Known allergy to any component of the vaccine
- •Allergic reaction or anaphylactic reaction to any previous vaccine
- •Known immunodeficiency disorder
- •Known HIV-infected mother
- •Known thrombocytopenia or coagulation disorder
- •On immunosuppressive medication
- •Administration or planned administration of any immunoglobulin or blood product since birth
- •Severe birth defect requiring ongoing medical care
- •Chronic or progressive disease
- •Seizure disorder
- •History of invasive pneumococcal, meningococcal or Haemophilus influenzae type b diseases, or tetanus, measles, pertussis or diphtheria infections
- •Receipt of any 2 month vaccines through the EPI program (Arms A-F) or receipt of PCV (Arm G)
- •Family plans on giving the infant Quinvaxem or oral polio vaccine (Arms A-F)
结局指标
主要结局
proportion of children with antibody concentration ≥0.35µg/mL for individual pneumococcal serotypes
时间窗: 4 weeks post-primary series
The immunogenicity of PCV will be measured by ELISA in terms of serotype-specific IgG antibody concentrations. Primary comparisons between arms will be made in terms of the proportion of children with antibody concentration ≥0.35µg/mL for the ten serotypes included in both PCVs. An overall conclusion for between arm comparisons will be based on the rejection of at least seven out of the ten individual serotype null hypotheses.
次要结局
- proportion of children with pneumococcal serotype-specific opsonisation index (OI) ≥8(four weeks post-primary series)
- proportion of children with four-fold rise in pneumococcal serotype-specific IgG(change from pre-booster to four weeks post-booster)
- NP carriage rate of H. influenzae(18 months of age)
- proportion of children with pneumococcal serotype-specific OI ≥8(four weeks post-booster)
- NP carriage rate of NTHi(18 months of age)
- NP carriage rate of vaccine-type (VT) Streptococcus pneumoniae (S. pneumoniae)(12 months of age)
- NP carriage rate of non-VT S. pneumoniae(18 months of age)
- geometric mean concentration (GMC) of pneumococcal serotype-specific IgG(four weeks post-primary series)
- median number of pneumococcal PS-specific memory B cells(18 months of age)
- Density of NP carriage of H. influenzae(12 months of age)
- NP carriage rate of VT S. pneumoniae(24 months of age)
- median number of pneumococcal polysaccharide (PS)-specific memory B cells(four weeks post-booster)
- median proportion of pneumococcal PS-specific memory B cells(18 months of age)
- Density of NP carriage of S. pneumoniae(12 months of age)