A Phase 3, Randomized, Double-Blind Study of the Safety, Tolerability, Lot-to-Lot Consistency, Immunogenicity & Non-Interference With Concomitant Vaccinations of Serum Institute of PNEUMOSIL in Healthy Infants in The Gambia
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 2,250
- 试验地点
- 2
- 主要终点
- Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 1
研究概览
简要总结
This study will examine the consistency of 3 batches of the Pneumosil vaccine by looking at the immune response in infants. In addition, the study will compare the immunogenicity of the Pneumosil vaccine to another WHO-prequalified vaccine, Synflorix.
详细描述
This is a randomized, active-controlled, double-blind, Phase 3 study in 2,250 healthy infants (6 to 8 weeks of age). Subjects will receive 3 doses of either PNEUMOSIL (3 groups receiving vaccine from different lots) or Synflorix (1 group) at 6, 10, and 14 weeks of age. The first 675 randomized subjects will receive a booster dose of either PNEUMOSIL or Synflorix at 9 months of age that matches the treatment assignment for the priming phase. Standard EPI vaccinations in The Gambia will be given concomitantly with all 4 doses of the study vaccines. Out of the 675 booster subjects, subjects who consented for further evaluation will participate for the assessment of immune persistence 12 (+1) months after the booster vaccination
The primary objectives are to demonstrate that the three lots of the Pneumosil vaccine is consistent by evaluating the immune responses, and to demonstrate that the immune responses generated by Pneumosil are non-inferior to those generated by Synflorix. The safety and tolerability of Pneumosil will also be evaluated.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •They are healthy infants based on medical history and clinical assessment.
- •They are between 6 and 8 weeks (ie 42 to 56 days) old, inclusive.
- •Subject's parent must provide voluntary written/thumb-printed informed consent and be willing to comply with study requirements and procedures.
排除标准
- •Use of any investigational medicinal product prior to randomization.
- •Previous vaccination against or infection with S. pneumoniae.
- •History of anaphylactic shock or an allergic reaction to any prior vaccination.
- •Any fever, illness (including malaria).
- •Receipt of another vaccine within 30 days of study start.
- •Chronic administration of an immunosuppressant or administration of immunoglobulins
- •History of blood disorder, primary immunodeficiency, or a sibling who has such a diagnosis or who died of suddenly without apparent cause.
- •History of meningitis, seizures or any neurological disorder.
结局指标
主要结局
Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 1
时间窗: 7 days (including day of vaccination)
In the primary reactogenicity cohort, local and systemic reactogenicity of the study vaccine was evaluated through day 6 for severity by toxicity grading scale (0 \[none\], 1 \[mild\], 2 \[moderate\], 3 \[severe\], 4 \[life threatening\].
Number and Percentage of All SAEs by Severity and Relatedness
时间窗: 4 weeks post last vaccination
All subjects were followed up for SAEs till 4 weeks post vaccination dose 3 and subjects in the booster cohort were followed up for SAEs till 4 weeks post booster vaccination
Anti Fimbriae 2/3 IgG GMCs for the Pertussis Antigen
时间窗: 4 weeks after the third dose
Anti fimbriae 2/3 IgG GMCs for the pertussis antigen
Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 2
时间窗: 7 days (including day of vaccination)
In the primary reactogenicity cohort, local and systemic reactogenicity of the study vaccine was evaluated through day 6 for severity by toxicity grading scale (0 \[none\], 1 \[mild\], 2 \[moderate\], 3 \[severe\], 4 \[life threatening\].
Serotype-specific Geometric Mean Concentration of IgG Antibody
时间窗: 4 weeks after the third dose
Serotype-specific concentrations of immunoglobulin G (IgG) antibody measured by ELISA
Number and Percentage of Subjects With EPI Vaccine Immune Responses (Diphtheria, Tetanus, Hepatitis B, Hib, Polio and Rotavirus)
时间窗: 4 weeks after the third dose
Subjects with 1) anti-diphtheria toxoid (DT) and anti-tetanus toxoid (DT) IgG concentration ≥ 0.1 IU/mL; 2) anti-Hepatitis B surface antigen (HBsAg) IgG concentration ≥ 10 mIU/mL; 3) anti-Hib (polyribosylribitol phosphate \[PRP\]) IgG concentration ≥ 0.15 µg/mL; 4) anti-poliovirus types 1, 2 and 3 neutralizing antibody titers ≥ 1:8; 5) anti-rotavirus IgA concentration ≥ 20 U/mL.
Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Booster
时间窗: 7 days (including day of vaccination)
In the primary reactogenicity cohort, local and systemic reactogenicity of the study vaccine was evaluated through day 6 for severity by toxicity grading scale (0 \[none\], 1 \[mild\], 2 \[moderate\], 3 \[severe\], 4 \[life threatening\].
Number and Percentage of All AEs Including SAEs Occurring in Greater Than 1% Subjects by Severity and Relatedness
时间窗: 4 weeks post last vaccination
All subjects were followed up for AEs till 4 weeks post vaccination dose 3 and subjects in the booster cohort were followed up for AEs till 4 weeks post booster vaccination
Number and Percentage of Subjects With Serotype-specific IgG Antibody Responses ≥ 0.35 μg/mL
时间窗: 4 weeks after the third dose
Number and Percentage of subjects with serotype-specific IgG Antibody Responses ≥ 0.35 μg/mL
Anti-pertussis Toxoid GMCs for the Pertussis Antigen
时间窗: 4 weeks after the third dose
Anti-pertussis toxoid GMCs for the pertussis antigen
Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 3
时间窗: 7 days (including day of vaccination)
In the primary reactogenicity cohort, local and systemic reactogenicity of the study vaccine was evaluated through day 6 for severity by toxicity grading scale (0 \[none\], 1 \[mild\], 2 \[moderate\], 3 \[severe\], 4 \[life threatening\].
次要结局
- Number and Percentage of Subjects With Functional Antibody Responses(4 weeks after the third dose)
- Comparison of Serotype-specific Geometric Mean Concentration of IgG Antibody Response 4 Weeks After a 3-dose Primary Series to 4 Weeks After a Booster Dose(4 weeks post booster vaccination)
- Number and Percentage of Subjects With 6A and 19A Serotype-specific Concentrations of Immunoglobulin G Antibody(4 weeks after the third dose)
- 6A and 19A Serotype Specific Geometric Mean Concentration of IgG Antibody(4 weeks after the third dose)
- Serotype-specific OPA Geometric Mean Titer(4 weeks after the third dose)
- Comparison of Functional Response (OPA) From 4 Weeks After a 3-dose Primary Series to 4 Weeks After a Booster Dose(4 weeks post booster vaccination)
- Serotype-specific OPA GMT and Treatment-Group GMT Ratios 4 Weeks After a Booster Dose(4 weeks post booster vaccination)
- Number and Percentage of Subjects With EPI Vaccine Immune Responses (Measles, Rubella and Yellow Fever)(4 weeks post booster vaccination)
- Serotype-specific Geometric Mean Concentration of IgG Antibody Response and Treatment-Group GMC Ratios 4 Weeks After a Booster Dose(4 weeks post booster vaccination)