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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
2,250
Medical Research Council (MRC) Unit, The Gambia
Fajara, The Gambia
Serotype-specific Geometric Mean Concentration of IgG Antibody
Serotype-specific concentrations of immunoglobulin G (IgG) antibody measured by ELISA
Time frame: 4 weeks after the third dose
Number and Percentage of Subjects With Serotype-specific IgG Antibody Responses ≥ 0.35 μg/mL
Number and Percentage of subjects with serotype-specific IgG Antibody Responses ≥ 0.35 μg/mL
Time frame: 4 weeks after the third dose
Serotype-specific Geometric Mean Concentration of IgG Antibody
Serotype-specific immunoglobulin G (IgG) geometric mean concentration (GMC) 4 weeks after the primary series of PNEUMOSIL/Synflorix co-administered with pentavalent, RV and polio vaccines.
Time frame: 4 weeks after the third dose
Number and Percentage of Subjects With EPI Vaccine Immune Responses (Diphtheria, Tetanus, Hepatitis B, Hib, Polio and Rotavirus)
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.
Time frame: 4 weeks after the third dose
Anti-pertussis Toxoid GMCs for the Pertussis Antigen
Anti-pertussis toxoid GMCs for the pertussis antigen
Time frame: 4 weeks after the third dose
Anti Fimbriae 2/3 IgG GMCs for the Pertussis Antigen
Anti fimbriae 2/3 IgG GMCs for the pertussis antigen
Time frame: 4 weeks after the third dose
Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 1
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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 \[life threatening\].
Time frame: 7 days (including day of vaccination)
Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 2
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 \[life threatening\].
Time frame: 7 days (including day of vaccination)
Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 3
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 \[life threatening\].
Time frame: 7 days (including day of vaccination)
Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Booster
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 \[life threatening\].
Time frame: 7 days (including day of vaccination)
Number and Percentage of All AEs Including SAEs Occurring in Greater Than 1% Subjects by Severity and Relatedness
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
Time frame: 4 weeks post last vaccination
Number and Percentage of All SAEs by Severity and Relatedness
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
Time frame: 4 weeks post last vaccination
Number and Percentage of Subjects With 6A and 19A Serotype-specific Concentrations of Immunoglobulin G Antibody
Subjects with 6A and 19A serotype-specific concentrations of immunoglobulin G (IgG) antibody measured by ELISA
Time frame: 4 weeks after the third dose
6A and 19A Serotype Specific Geometric Mean Concentration of IgG Antibody
6A and 19A Serotype Specific Immune Responses in terms of IgG GMCs measured by ELISA
Time frame: 4 weeks after the third dose
Number and Percentage of Subjects With Functional Antibody Responses
Serotype-specific functional antibody titer measured by OPA
Time frame: 4 weeks after the third dose
Serotype-specific OPA Geometric Mean Titer
Serotype-specific functional antibody titer measured by OPA and expressed as OPA GMT in a subset
Time frame: 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
Comparison of Serotype-specific booster responses (antibody concentrations) measured by ELISA from 4 weeks after a 3-dose primary series to 4 weeks after a booster dose
Time frame: 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
Comparison of Serotype-specific booster responses (antibody concentrations) to PNEUMOSIL in comparison to Synflorix 4 weeks after a booster dose
Time frame: 4 weeks post booster vaccination
Comparison of Functional Response (OPA) From 4 Weeks After a 3-dose Primary Series to 4 Weeks After a Booster Dose
Comparison of Serotype-specific booster responses (functional response-OPA) from 4 weeks after a 3-dose primary series to 4 weeks after a booster dose
Time frame: 4 weeks post booster vaccination
Serotype-specific OPA GMT and Treatment-Group GMT Ratios 4 Weeks After a Booster Dose
Comparison of Serotype-specific booster responses (functional response) to PNEUMOSIL in comparison to Synflorix 4 weeks after a booster dose
Time frame: 4 weeks post booster vaccination
Number and Percentage of Subjects With EPI Vaccine Immune Responses (Measles, Rubella and Yellow Fever)
Anti-measles IgG, anti-rubella IgG and anti-yellow fever neutralizing antibody titer
Time frame: 4 weeks post booster vaccination