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

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

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.

Study Overview

• Status: Completed
• Conditions: Pneumonia, Pneumococcal
• Intervention / Treatment: Biological: Pneumosil; Biological: 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.

• Study Type: Interventional
• Enrollment (Actual): 2250
• Phase: Phase 3

Contacts and Locations

Study Locations

• Gambia
  • Fajara, Gambia
    • Medical Research Council (MRC) Unit, The Gambia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 1 month (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pneumosil Lot 1	Biological: Pneumosil; 10-Valent Pneumococcal Conjugate Vaccine
Experimental: Pneumosil Lot 2	Biological: Pneumosil; 10-Valent Pneumococcal Conjugate Vaccine
Experimental: Pneumosil Lot 3	Biological: Pneumosil; 10-Valent Pneumococcal Conjugate Vaccine
Active Comparator: Synflorix	Biological: Synflorix; Pneumococcal conjugate vaccine (Non-Typeable Haemophilus influenzae (NTHi) protein D, diphtheria or tetanus toxoid conjugates) adsorbed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serotype-specific Geometric Mean Concentration of IgG Antibody	Serotype-specific concentrations of immunoglobulin G (IgG) antibody measured by ELISA	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	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.	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.	4 weeks after the third dose
Anti-pertussis Toxoid GMCs for the Pertussis Antigen	Anti-pertussis toxoid GMCs for the pertussis antigen	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	4 weeks after the third dose
Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 1	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].	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].	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].	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].	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	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	4 weeks post last vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	4 weeks after the third dose
Number and Percentage of Subjects With Functional Antibody Responses	Serotype-specific functional antibody titer measured by OPA	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	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	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	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	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	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	4 weeks post booster vaccination

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportions and Treatment Group Difference in Proportions of IgG Responders 1 Year Post Booster	Treatment group proportions and treatment-group difference in proportions of IgG responders (IgG concentration ≥ 0.35 μg/mL)	One Year Post Booster Vaccination
Serotype-specific Geometric Mean Concentration of IgG Antibody Response and Treatment-Group GMC Ratios One Year Post Booster	Comparison of Serotype-specific immune persistence responses (antibody concentrations) to PNEUMOSIL in comparison to Synflorix one year post booster	One year post booster vaccination
Comparison of Serotype-specific Geometric Mean Concentration of IgG Antibody Response 4 Weeks After a Booster Dose to One Year After a Booster Dose	Comparison of Serotype-specific responses (antibody concentrations) measured by ELISA from 4 weeks after a booster dose to one year after a booster dose	One year post booster vaccination
Treatment Group Proportions and Treatment-group Difference in Proportions of Functional Antibody Responders (OPA) One Year Post Booster	Serotype-specific functional antibody titer measured by OPA	One year post booster vaccination
Serotype-specific OPA Geometric Mean Titer One Year Post Booster	Serotype-specific functional antibody titer measured by OPA and expressed as OPA GMT in a subset one year post booster	One year post booster vaccination
Comparison of Functional Response (OPA) From 4 Weeks After a Booster Dose to One Year Post Booster Dose	Comparison of Serotype-specific booster responses (functional response-OPA) from 4 weeks after a booster dose to one year post booster	One year post booster vaccination

Collaborators and Investigators

• Sponsor: PATH
• Investigators: Principal Investigator: Ed Clarke, Medical Research Council (MRC) Unit, The Gambia

Publications and helpful links

General Publications

• Clarke E, Bashorun A, Adigweme I, Badjie Hydara M, Umesi A, Futa A, Ochoge M, Obayemi D, Edem B, Saidy-Jah E, Onwuchekwa C, Dhere R, Sethna V, Kampmann B, Goldblatt D, Taylor D, Andi-Lolo I, Hosken N, Antony K, Innis BL, Alderson MR, Lamola S. Immunogenicity and safety of a novel ten-valent pneumococcal conjugate vaccine in healthy infants in The Gambia: a phase 3, randomised, double-blind, non-inferiority trial. Lancet Infect Dis. 2021 Jun;21(6):834-846. doi: 10.1016/S1473-3099(20)30735-0. Epub 2021 Jan 28.

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2017
• Primary Completion (Actual): June 6, 2018
• Study Completion (Actual): May 9, 2019

Study Registration Dates

• First Submitted: June 21, 2017
• First Submitted That Met QC Criteria: June 21, 2017
• First Posted (Actual): June 23, 2017

Study Record Updates

• Last Update Posted (Actual): July 14, 2020
• Last Update Submitted That Met QC Criteria: June 30, 2020
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumonia, Bacterial; Pneumococcal Infections; Pneumonia, Pneumococcal
• Other Study ID Numbers: VAC-056

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No