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Completed

NCT Number: NCT03197376

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

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.

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Key information

Conditions

Pneumonia, Pneumococcal Bacterial Infections Bacterial Infections and Mycoses Gram-Positive Bacterial Infections Infections Lung Diseases Pneumococcal Infections Pneumonia Pneumonia, Bacterial Respiratory Tract Diseases Respiratory Tract Infections Streptococcal Infections

Age range

6 week–8 week

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Medical Research Council (MRC) Unit, The Gambia

Fajara, The Gambia

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Pneumosil

Biological

10-Valent Pneumococcal Conjugate Vaccine

Synflorix

Biological

Pneumococcal conjugate vaccine (Non-Typeable Haemophilus influenzae (NTHi) protein D, diphtheria or tetanus toxoid conjugates) adsorbed

Primary outcomes

  1. Serotype-specific Geometric Mean Concentration of IgG Antibody

    Time frame: 4 weeks after the third dose

    Serotype-specific concentrations of immunoglobulin G (IgG) antibody measured by ELISA

  2. Number and Percentage of Subjects With Serotype-specific IgG Antibody Responses ≥ 0.35 μg/mL

    Time frame: 4 weeks after the third dose

    Number and Percentage of subjects with serotype-specific IgG Antibody Responses ≥ 0.35 μg/mL

  3. Serotype-specific Geometric Mean Concentration of IgG Antibody

    Time frame: 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.

  4. Number and Percentage of Subjects With EPI Vaccine Immune Responses (Diphtheria, Tetanus, Hepatitis B, Hib, Polio and Rotavirus)

    Time frame: 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.

  5. Anti-pertussis Toxoid GMCs for the Pertussis Antigen

    Time frame: 4 weeks after the third dose

    Anti-pertussis toxoid GMCs for the pertussis antigen

  6. Anti Fimbriae 2/3 IgG GMCs for the Pertussis Antigen

    Time frame: 4 weeks after the third dose

    Anti fimbriae 2/3 IgG GMCs for the pertussis antigen

  7. Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 1

    Time frame: 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].

  8. Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 2

    Time frame: 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].

  9. Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 3

    Time frame: 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].

  10. Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Booster

    Time frame: 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].

  11. Number and Percentage of All AEs Including SAEs Occurring in Greater Than 1% Subjects by Severity and Relatedness

    Time frame: 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

  12. Number and Percentage of All SAEs by Severity and Relatedness

    Time frame: 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

Secondary outcomes

  1. Number and Percentage of Subjects With 6A and 19A Serotype-specific Concentrations of Immunoglobulin G Antibody

    Time frame: 4 weeks after the third dose

    Subjects with 6A and 19A serotype-specific concentrations of immunoglobulin G (IgG) antibody measured by ELISA

  2. 6A and 19A Serotype Specific Geometric Mean Concentration of IgG Antibody

    Time frame: 4 weeks after the third dose

    6A and 19A Serotype Specific Immune Responses in terms of IgG GMCs measured by ELISA

  3. Number and Percentage of Subjects With Functional Antibody Responses

    Time frame: 4 weeks after the third dose

    Serotype-specific functional antibody titer measured by OPA

  4. Serotype-specific OPA Geometric Mean Titer

    Time frame: 4 weeks after the third dose

    Serotype-specific functional antibody titer measured by OPA and expressed as OPA GMT in a subset

  5. 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

    Time frame: 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

  6. Serotype-specific Geometric Mean Concentration of IgG Antibody Response and Treatment-Group GMC Ratios 4 Weeks After a Booster Dose

    Time frame: 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

  7. Comparison of 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

    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

  8. Serotype-specific OPA GMT and Treatment-Group GMT Ratios 4 Weeks After a Booster Dose

    Time frame: 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

  9. Number and Percentage of Subjects With EPI Vaccine Immune Responses (Measles, Rubella and Yellow Fever)

    Time frame: 4 weeks post booster vaccination

    Anti-measles IgG, anti-rubella IgG and anti-yellow fever neutralizing antibody titer

Other outcomes

  1. Proportions and Treatment Group Difference in Proportions of IgG Responders 1 Year Post Booster

    Time frame: One Year Post Booster Vaccination

    Treatment group proportions and treatment-group difference in proportions of IgG responders (IgG concentration ≥ 0.35 μg/mL)

  2. Serotype-specific Geometric Mean Concentration of IgG Antibody Response and Treatment-Group GMC Ratios One Year Post Booster

    Time frame: One year post booster vaccination

    Comparison of Serotype-specific immune persistence responses (antibody concentrations) to PNEUMOSIL in comparison to Synflorix one year post booster

  3. Comparison of Serotype-specific Geometric Mean Concentration of IgG Antibody Response 4 Weeks After a Booster Dose to One Year After a Booster Dose

    Time frame: One year post booster vaccination

    Comparison of Serotype-specific responses (antibody concentrations) measured by ELISA from 4 weeks after a booster dose to one year after a booster dose

  4. Treatment Group Proportions and Treatment-group Difference in Proportions of Functional Antibody Responders (OPA) One Year Post Booster

    Time frame: One year post booster vaccination

    Serotype-specific functional antibody titer measured by OPA

  5. Serotype-specific OPA Geometric Mean Titer One Year Post Booster

    Time frame: One year post booster vaccination

    Serotype-specific functional antibody titer measured by OPA and expressed as OPA GMT in a subset one year post booster

  6. Comparison of Functional Response (OPA) From 4 Weeks After a Booster Dose to One Year Post Booster Dose

    Time frame: One year post booster vaccination

    Comparison of Serotype-specific booster responses (functional response-OPA) from 4 weeks after a booster dose to one year post booster

Sponsors and collaborators

Lead sponsor

PATH

Other

Registry information

Official study title

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

Important dates

Study start
2017
Primary completion
2018
Study completion
2019
First posted
Jun 23, 2017
Registry last updated
Jul 14, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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