Phase 3 Study of 10-valent Pneumococcal Conjugate Vaccine (PNEUMOSIL) in Healthy Infants

Phase 3

Completed

Conditions: Pneumonia, Pneumococcal

Interventions: Biological: Pneumosil
Biological: Synflorix

Registration Number: NCT03197376

Lead Sponsor: PATH

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 2250

Inclusion Criteria

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.

Exclusion Criteria

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pneumosil Lot 3	Pneumosil	Pneumosil Lot 3
Pneumosil Lot 1	Pneumosil	Pneumosil Lot 1
Synflorix	Synflorix	Synflorix
Pneumosil Lot 2	Pneumosil	Pneumosil Lot 2

Primary Outcome Measures

Name	Time	Method
Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 1	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	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	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	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	4 weeks after the third dose	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.
Number and Percentage of Subjects With EPI Vaccine Immune Responses (Diphtheria, Tetanus, Hepatitis B, Hib, Polio and Rotavirus)	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	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	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	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	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	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 \[life threatening\].

Secondary Outcome Measures

Name	Time	Method
Number and Percentage of Subjects With Functional Antibody Responses	4 weeks after the third dose	Serotype-specific functional antibody titer measured by OPA
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	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
Number and Percentage of Subjects With 6A and 19A Serotype-specific Concentrations of Immunoglobulin G Antibody	4 weeks after the third dose	Subjects with 6A and 19A serotype-specific concentrations of immunoglobulin G (IgG) antibody measured by ELISA
6A and 19A Serotype Specific Geometric Mean Concentration of IgG Antibody	4 weeks after the third dose	6A and 19A Serotype Specific Immune Responses in terms of IgG GMCs measured by ELISA
Serotype-specific OPA Geometric Mean Titer	4 weeks after the third dose	Serotype-specific functional antibody titer measured by OPA and expressed as OPA GMT in a subset
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	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
Serotype-specific OPA GMT and Treatment-Group GMT Ratios 4 Weeks After a Booster Dose	4 weeks post booster vaccination	Comparison of Serotype-specific booster responses (functional response) to PNEUMOSIL in comparison to Synflorix 4 weeks after a booster dose
Number and Percentage of Subjects With EPI Vaccine Immune Responses (Measles, Rubella and Yellow Fever)	4 weeks post booster vaccination	Anti-measles IgG, anti-rubella IgG and anti-yellow fever neutralizing antibody titer
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	Comparison of Serotype-specific booster responses (antibody concentrations) to PNEUMOSIL in comparison to Synflorix 4 weeks after a booster dose