Study of 10-valent Pneumococcal Conjugate Vaccine (Pneumosil) Administered in a 2+1 Schedule to Healthy Infants

NCT03896477 | Completed Phase 3 Results DMC

• 2 other identifiers: CVIA-074PACTR201907754270299
• Study Type: interventional
• Target: 660
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objectives of this study are to evaluate the immunogenicity (antibody response) and safety and tolerability of a 2-dose primary series and booster dose (2+1 schedule) of Pneumosil co-administered with routine pediatric vaccines in healthy infants in The Gambia.

Conditions

Pneumonia, Pneumococcal

Outcome Measures

Primary Outcomes (4)

• Geometric Mean Concentration (GMC) of Serotype-specific Immunoglobulin G (IgG) Antibodies Four Weeks Post-Booster

  The IgG antibody concentration to each of the 10 serotypes contained in Pneumosil was measured by enzyme-linked immunosorbent assay (ELISA) in serum samples collected 4 weeks after the booster dose (Visit 6). The pneumococcal serotype-specific IgG ELISAs were performed using the World Health Organisation (WHO) reference assay at the WHO Pneumococcal Serology Reference Laboratory, at the Institute of Child Health, University College London, United Kingdom (UK), where the assay was validated.

  4 weeks post booster dose

• Number of Participants With Solicited Local and Systemic Adverse Events (AEs) Through Day 6 Following Any Vaccination

  Solicited local reactions included tenderness, erythema/redness and induration/swelling at the study vaccine injection site. Solicited systemic reactions included cutaneous rash, fever (based on axillary temperature), irritability, drowsiness, and decreased appetite. The severity of all solicited AEs was graded from mild (Grade 1) to potentially life threatening (Grade 4), based on protocol-defined criteria that were derived from Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (Version 2.0, November 2014).

  Day 0 to Day 6 after each vaccination

• Number of Participants With Unsolicited Treatment-emergent Adverse Events (TEAEs)

  AEs include any intercurrent illness or injury during the study, clinically significant worsening of a preexisting condition, and any solicited AE that occurred or was ongoing 6 days after study vaccine administration. A TEAE is an event that was not present prior to administration of the study vaccine, or increased in intensity after administration of the study vaccine. Unsolicited AEs were graded using the scale below: Grade 1: Mild; asymptomatic or mild symptoms; intervention not indicated. Grade 2: Moderate; minimal, local, or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. Related AEs are AEs where the Investigator determined a reasonable causal relationship between the vaccine administered and the AE based on medical judgement.

  AEs were collected from first dose at age 6 weeks up to 9 months of age, and then from the date of the booster vaccination through 4 weeks post vaccination; approximately 8.5 months overall.

• Number of Participants With Serious Adverse Events (SAEs)

  An SAE was a specific AE that: * Resulted in death. * Was life-threatening. * Required inpatient hospitalization or prolongation of an existing hospitalization. * Resulted in a persistent or significant disability or incapacity. * Resulted in a congenital anomaly or birth defect

  SAEs were collected from first dose at age 6 weeks up to 4 weeks post booster vaccination, approximately 15.5 months overall.

Secondary Outcomes (14)

• Geometric Mean Titers (GMT) of Serotype-specific Opsonophagocytic Activity (OPA) Four Weeks Post-Booster

  4 weeks post booster dose

• Percentage of Participants With Serotype-specific Serum IgG Antibody Concentrations ≥ 0.35 μg/mL Four Weeks Post-Booster

  4 weeks post booster dose

• Percentage of Participants With Serotype-specific Serum IgG Antibody Concentrations ≥ 1.0 μg/mL Four Weeks Post-Booster

  4 weeks post booster dose

• Percentage of Participants With Serotype-specific Serum OPA Titers ≥ 8 Four Weeks Post-Booster

  4 weeks post booster dose

• Percentage of Participants With Serotype-specific Serum IgG Antibody Concentrations ≥ 0.35 μg/mL Four Weeks After Completion of Primary Vaccinations

  4 weeks after completion of primary vaccinations (at age 18 weeks)

Study Arms (3)

Pneumosil

EXPERIMENTAL

Infants received two primary vaccinations with Pneumosil, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age.

Biological: Pneumosil

Synflorix

ACTIVE COMPARATOR

Infants received two primary vaccinations with Synflorix, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age.

Biological: Synflorix

Prevenar 13

ACTIVE COMPARATOR

Infants received two primary vaccinations with Prevenar 13, the first at age 6 weeks and the second at age 14 weeks. A booster vaccination was given between 9 and 16 months of age.

Biological: Prevenar 13

Interventions

Pneumosil BIOLOGICAL

One single dose contains 2 μg of polysaccharide for serotypes 1, 5, 6A, 7F, 9V, 14, 19A, 19F and 23F, and 4 μg for serotype 6B formulated with aluminium phosphate as an adjuvant in an appropriate buffer

Also known as: Serum Institute of India Pneumococcal conjugate vaccine (SIIPL-PCV )

Pneumosil

Prevenar 13 BIOLOGICAL

One single dose contains 2.2 µg of the following pneumococcal polysaccharides serotypes - 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F - and 4.4 µg of pneumococcal polysaccharide serotype 6B, all conjugated to CRM197 and absorbed onto aluminum phosphate

Prevenar 13

Synflorix BIOLOGICAL

One single dose contains 1 μg of polysaccharide for serotypes 1, 5, 6B, 7F, 9V, 14, and 23F, and 3μg of serotypes 4, 18C, and 19F formulated with aluminum phosphate as an adjuvant.

Also known as: Pneumococcal polysaccharide conjugate vaccine (adsorbed)

Synflorix

Eligibility Criteria

• Age: 42 Days - 56 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Healthy infants based on medical history and clinical assessment.
• 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.
• Subjects must have been born full-term, have a weight-to-height Z score of ≥ -2 at the time of enrollment (WHO child growth standard), and be ≥ 3.5 kg at randomization.
• Subject's parents must be available for the duration of trial participation

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 study 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 suddenly without apparent cause.
• History of meningitis, seizures or any neurological disorder.
• Exposure to human immunodeficiency virus (HIV) by history.

Sponsors & Collaborators

• PATH: lead
• Serum Institute of India Pvt. Ltd.: collaborator
• Medical Research Council Unit, The Gambia: collaborator
• University College, London: collaborator
• FHI 360: collaborator

Study Sites (1)

Medical Research Council Unit, The Gambia at the London School of Hygiene and Tropical Medicine (MRCG at LSHTM)

Banjul, The Gambia

Location

Related Publications (1)

• Adigweme I, Futa A, Saidy-Jah E, Edem B, Akpalu E, Dibbasey T, Sethna V, Dhere R, Kampmann B, Bengt C, Sirr J, Hosken N, Goldblatt D, Antony K, Alderson MR, Lamola S, Clarke E. Immunogenicity and safety of a 10-valent pneumococcal conjugate vaccine administered as a 2 + 1 schedule to healthy infants in The Gambia: a single-centre, double-blind, active-controlled, randomised, phase 3 trial. Lancet Infect Dis. 2023 May;23(5):609-620. doi: 10.1016/S1473-3099(22)00734-4. Epub 2023 Jan 10.

  PMID: 36638819 DERIVED

MeSH Terms

Conditions

Pneumonia, Pneumococcal

Interventions

13-valent pneumococcal vaccine; 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: Mark Alderson
• Organization: PATH

malderson@path.org

+ 206.302.4859

Study Officials

• Ed Clarke, MB ChB, PhD

  MRCG at LSHTM

  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: March 22, 2019
• First Posted: April 1, 2019
• Study Start: July 18, 2019
• Primary Completion: December 17, 2020
• Study Completion: December 17, 2020
• Last Updated: April 20, 2022
• Results First Posted: April 20, 2022

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)