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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03197376
Recruitment Status : Completed
First Posted : June 23, 2017
Results First Posted : September 11, 2019
Last Update Posted : July 14, 2020
Sponsor:
Information provided by (Responsible Party):
PATH

Study Description
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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.

Condition or disease Intervention/treatment Phase
Pneumonia, Pneumococcal Biological: Pneumosil Biological: Synflorix Phase 3

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official 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
Actual Study Start Date : June 21, 2017
Actual Primary Completion Date : June 6, 2018
Actual Study Completion Date : May 9, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vaccines

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


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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 Outcome Measures:
  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


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   6 Weeks to 8 Weeks   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03197376


Locations
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Gambia
Medical Research Council (MRC) Unit, The Gambia
Fajara, Gambia
Sponsors and Collaborators
PATH
Investigators
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Principal Investigator: Ed Clarke Medical Research Council (MRC) Unit, The Gambia
  Study Documents (Full-Text)

Documents provided by PATH:
Study Protocol  [PDF] June 1, 2018
Statistical Analysis Plan  [PDF] June 28, 2018

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: PATH
ClinicalTrials.gov Identifier: NCT03197376    
Other Study ID Numbers: VAC-056
First Posted: June 23, 2017    Key Record Dates
Results First Posted: September 11, 2019
Last Update Posted: July 14, 2020
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Pneumonia, Pneumococcal
Pneumonia
Respiratory Tract Infections
Infections
Lung Diseases
Respiratory Tract Diseases
 Pneumococcal Infections
Streptococcal Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Pneumonia, Bacterial