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

NCT03197376 | Completed Phase 3 Results DMC

• 1 other identifier: VAC-056
• Study Type: interventional
• Target: 2,250
• Locations: 1 country
• Sites: 1

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.

Conditions

Pneumonia, Pneumococcal

Outcome Measures

Primary Outcomes (12)

• 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 Outcomes (9)

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

  4 weeks after the third dose

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

  4 weeks after the third dose

• Number and Percentage of Subjects With Functional Antibody Responses

  4 weeks after the third dose

• Serotype-specific OPA Geometric Mean Titer

  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

  4 weeks post booster vaccination

Other Outcomes (6)

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

  One Year Post Booster Vaccination

• Serotype-specific Geometric Mean Concentration of IgG Antibody Response and Treatment-Group GMC Ratios 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

  One year post booster vaccination

Study Arms (4)

Pneumosil Lot 1

EXPERIMENTAL

Pneumosil Lot 1

Biological: Pneumosil

Pneumosil Lot 2

EXPERIMENTAL

Pneumosil Lot 2

Biological: Pneumosil

Pneumosil Lot 3

EXPERIMENTAL

Pneumosil Lot 3

Biological: Pneumosil

Synflorix

ACTIVE COMPARATOR

Synflorix

Biological: Synflorix

Interventions

Pneumosil BIOLOGICAL

10-Valent Pneumococcal Conjugate Vaccine

Pneumosil Lot 1; Pneumosil Lot 2; Pneumosil Lot 3

Synflorix BIOLOGICAL

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

Synflorix

Eligibility Criteria

• Age: 6 Weeks - 8 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• PATH: lead

Study Sites (1)

Medical Research Council (MRC) Unit, The Gambia

Fajara, The Gambia

Location

Related Publications (1)

• 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.

  PMID: 33516293 DERIVED

MeSH Terms

Conditions

Pneumonia, Pneumococcal

Interventions

PHiD-CV vaccine

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Steve Lamola
• Organization: PATH

slamola@path.org

+ 1 206.302.6067

Study Officials

• Ed Clarke

  Medical Research Council (MRC) Unit, The Gambia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2017
• First Posted: June 23, 2017
• Study Start: June 21, 2017
• Primary Completion: June 6, 2018
• Study Completion: May 9, 2019
• Last Updated: July 14, 2020
• Results First Posted: September 11, 2019

Record last verified: 2019-08

Locations

TH (1)