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

NCT ID: NCT03896477

Last Updated: 2022-04-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 660 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-18
• Study Completion Date: 2020-12-17

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.

Detailed Description

This study will provide data necessary to evaluate the safety and immunogenicity of Pneumosil when administered in an alternative schedule to the 3 dose primary schedule (3+0) evaluated in the Phase 3 pivotal trial (VAC-056; NCT03197376) - namely in a 2 dose primary and booster (2+1) schedule - and compare immunogenicity to that of both currently licensed second-generation pneumococcal conjugate vaccines (Synflorix and Prevenar 13) administered in the same 2+1 schedule.

In this prospective, single center, randomized, active-controlled, observer-blind, Phase 3 descriptive study, 660 healthy Gambian pneumococcal conjugate vaccine (PCV)-naïve infants will be randomized 1:1:1 to receive 3 doses of either Pneumosil, Synflorix or Prevenar 13 at 6 weeks, 14 weeks and 9-10 months of age. Standard Expanded Program on Immunization (EPI) vaccinations in The Gambia will be given concomitantly with all 3 doses of study vaccine.

The booster vaccination window was extended up to 18 months of age due to a pause in the study due to the coronavirus disease 2019 (COVID-19) pandemic. The study schedule for participants is as follows:

• Age 6 weeks: First primary vaccination dose administered
• Age 14 weeks: Second primary vaccination dose administered (8 weeks after first primary dose)
• Age 18 weeks: Blood sample for immunogenicity testing (4 weeks after second primary dose)
• Age 9-18 months: Blood sample for immunogenicity testing and booster vaccination dose administered
• Age 10-19 months: Blood sample for immunogenicity testing (4 weeks after booster dose)

Conditions

Pneumonia, Pneumococcal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Pneumosil

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.

Group Type: EXPERIMENTAL

Pneumosil

Intervention Type: 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

Synflorix

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.

Group Type: ACTIVE_COMPARATOR

Synflorix

Intervention Type: 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.

Prevenar 13

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.

Group Type: ACTIVE_COMPARATOR

Prevenar 13

Intervention Type: 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

Interventions

Pneumosil

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

Intervention Type: BIOLOGICAL

Prevenar 13

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

Intervention Type: BIOLOGICAL

Synflorix

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

Serum Institute of India Pneumococcal conjugate vaccine (SIIPL-PCV ); Pneumococcal polysaccharide conjugate vaccine (adsorbed)

Eligibility Criteria

Inclusion Criteria

• 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

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 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.

• Minimum Eligible Age: 42 Days
• Maximum Eligible Age: 56 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Serum Institute of India Pvt. Ltd.

INDUSTRY

Sponsor Role: collaborator

Medical Research Council Unit, The Gambia

OTHER

Sponsor Role: collaborator

University College, London

OTHER

Sponsor Role: collaborator

FHI 360

OTHER

Sponsor Role: collaborator

PATH

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ed Clarke, MB ChB, PhD

Role: PRINCIPAL_INVESTIGATOR

MRCG at LSHTM

Locations

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

Banjul, , The Gambia

Countries

The Gambia

References

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.

Reference Type: DERIVED

PMID: 36638819 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

PACTR201907754270299

Identifier Type: REGISTRY

Identifier Source: secondary_id

CVIA-074

Identifier Type: -

Identifier Source: org_study_id