Clinical trial NCT03197376: Phase 3 Study of 10-valent Pneumococcal Conjugate Vaccine (PNEUMOSIL) in Healthy Infants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumonia, Pneumococcal
Lead sponsor: PATH
Sponsor class: OTHER
First posted: 2017-06-23
Enrollment: 2250
Sex: ALL
Minimum age (years): 6
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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.

Primary outcomes:
measure: Serotype-specific Geometric Mean Concentration of IgG Antibody
timeFrame: 4 weeks after the third dose
measure: Number and Percentage of Subjects With Serotype-specific IgG Antibody Responses ≥ 0.35 μg/mL
timeFrame: 4 weeks after the third dose
measure: Serotype-specific Geometric Mean Concentration of IgG Antibody
timeFrame: 4 weeks after the third dose
measure: Number and Percentage of Subjects With EPI Vaccine Immune Responses (Diphtheria, Tetanus, Hepatitis B, Hib, Polio and Rotavirus)
timeFrame: 4 weeks after the third dose
measure: Anti-pertussis Toxoid GMCs for the Pertussis Antigen
timeFrame: 4 weeks after the third dose
measure: Anti Fimbriae 2/3 IgG GMCs for the Pertussis Antigen
timeFrame: 4 weeks after the third dose
measure: Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 1
timeFrame: 7 days (including day of vaccination)
measure: Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 2
timeFrame: 7 days (including day of vaccination)
measure: Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Vaccination 3
timeFrame: 7 days (including day of vaccination)
measure: Number and Percentage of Solicited Local and Systemic Reactogenicity by Severity- Booster
timeFrame: 7 days (including day of vaccination)
measure: Number and Percentage of All AEs Including SAEs Occurring in Greater Than 1% Subjects by Severity and Relatedness
timeFrame: 4 weeks post last vaccination
measure: Number and Percentage of All SAEs by Severity and Relatedness
timeFrame: 4 weeks post last vaccination
Secondary outcomes:
measure: Number and Percentage of Subjects With 6A and 19A Serotype-specific Concentrations of Immunoglobulin G Antibody
timeFrame: 4 weeks after the third dose
measure: 6A and 19A Serotype Specific Geometric Mean Concentration of IgG Antibody
timeFrame: 4 weeks after the third dose
measure: Number and Percentage of Subjects With Functional Antibody Responses
timeFrame: 4 weeks after the third dose
measure: Serotype-specific OPA Geometric Mean Titer
timeFrame: 4 weeks after the third dose
measure: 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
timeFrame: 4 weeks post booster vaccination
measure: Serotype-specific Geometric Mean Concentration of IgG Antibody Response and Treatment-Group GMC Ratios 4 Weeks After a Booster Dose
timeFrame: 4 weeks post booster vaccination
measure: Comparison of Functional Response (OPA) From 4 Weeks After a 3-dose Primary Series to 4 Weeks After a Booster Dose
timeFrame: 4 weeks post booster vaccination
measure: Serotype-specific OPA GMT and Treatment-Group GMT Ratios 4 Weeks After a Booster Dose
timeFrame: 4 weeks post booster vaccination
measure: Number and Percentage of Subjects With EPI Vaccine Immune Responses (Measles, Rubella and Yellow Fever)
timeFrame: 4 weeks post booster vaccination
Other outcomes:
measure: Proportions and Treatment Group Difference in Proportions of IgG Responders 1 Year Post Booster
timeFrame: One Year Post Booster Vaccination
measure: Serotype-specific Geometric Mean Concentration of IgG Antibody Response and Treatment-Group GMC Ratios One Year Post Booster
timeFrame: One year post booster vaccination
measure: Comparison of Serotype-specific Geometric Mean Concentration of IgG Antibody Response 4 Weeks After a Booster Dose to One Year After a Booster Dose
timeFrame: One year post booster vaccination
measure: Treatment Group Proportions and Treatment-group Difference in Proportions of Functional Antibody Responders (OPA) One Year Post Booster
timeFrame: One year post booster vaccination
measure: Serotype-specific OPA Geometric Mean Titer One Year Post Booster
timeFrame: One year post booster vaccination
measure: Comparison of Functional Response (OPA) From 4 Weeks After a Booster Dose to One Year Post Booster Dose
timeFrame: One year post booster vaccination
Locations:
city: Fajara
country: Gambia
facility: Medical Research Council (MRC) Unit, The Gambia
Study officials:
affiliation: Medical Research Council (MRC) Unit, The Gambia
name: Ed Clarke
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.