The Effect of Fractional Doses of Pneumococcal Conjugate Vaccines on Immunogenicity and Carriage in Kenyan Infants

NCT03489018 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: QA1075
• Study Type: interventional
• Target: 2,100
• Locations: 1 country
• Sites: 1

Brief Summary

Before the introduction of pneumonia vaccines in 2000, between 700,000 - 1 million children died each year as a result of infection with the bacteria Streptococcus pneumoniae and the resulting diseases, namely, meningitis, sepsis and pneumonia. Most of the deaths were in Africa and Asia. Where the vaccines have been introduced, they have been highly effective and have already reduced disease. However, at 10 USD per child, they are not affordable to most low-income countries without financial support from Gavi, the Vaccine Alliance. This project aims to assess whether lower doses of the two commercially available pneumonia vaccines can protect Kenyan infants as well as the full dose. The results could be used to increase the affordability of the pneumonia vaccine, and enable delivery of the vaccine to continue in the absence of Gavi support.

Conditions

Pneumococcal Infection; Streptococcus Pneumoniae Infection; Invasive Pneumococcal Disease, Protection Against

Keywords

Pneumococcal Vaccines;; Immunogenicity, Vaccine; 10-valent pneumococcal vaccine; 13-valent pneumococcal vaccine; Schedule; Pneumococcal Infection; Kenya; Infant; Vaccines, Conjugate; Humans; Immunization schedule; Streptococcus pneumoniae; vaccine; Dose-Response Relationship, immunologic; Equivalence Trial as Topic

Outcome Measures

Primary Outcomes (1)

• Immunogenicity: The ratio of IgG GMCs at 1-month post boost

  The ratio of the geometric mean concentrations of IgG after vaccination with 3 full or fractional doses of PCV

  4-weeks post-boost (approximately 10 months of age)

Secondary Outcomes (5)

• Immunogenicity: the proportion of children who 'seroconvert' to vaccine-serotypes after vaccination

  4-weeks post-primary series (approximately 18 weeks of age)

• The proportion of children with evidence of vaccine-serotype carriage

  Approximately 18 months of age

• The proportion of children with evidence of vaccine-serotype carriage

  Approximately 9 months of age

• The direct vaccine effectiveness of full/fractional doses of PCV13 against carriage of serotypes 6A and 19A

  Approximately 18 months of age

• Opsonophagocytic activity of vaccine-induced antibody to 4 serotypes

  Approximately 18 months of age

Other Outcomes (3)

• Immunogenicity: the geometric mean concentration (GMC) of serotype-specific IgG

  4-weeks post-primary series (approximately 18 weeks of age)

• Safety: the prevalence of adverse events following immunisation by arm

  Infants 6weeks-18 months of age

• Immunogenicity: The geometric mean concentration (GMC) of serotype-specific IgG after the primary series of the 2p+1 schedule, prior to boost (9 months of age) and at the end of study follow-up at 18 months of age.

  Approximately 9 and 18 months of age

Study Arms (7)

Full dose PCV13 (2p+1 schedule)

ACTIVE COMPARATOR

Full dose PCV13 administration in 2p+1 schedule

Biological: PCV13

40% dose PCV13 (2p+1 schedule)

EXPERIMENTAL

Fractional (40%) dose PCV13 administration in 2p+1 schedule

Biological: PCV13

20% dose PCV13 (2p+1 schedule)

EXPERIMENTAL

Fractional (20%) dose PCV13 administration in 2p+1 schedule

Biological: PCV13

Full dose PCV10 (2p+1 schedule)

ACTIVE COMPARATOR

Full dose PCV10 administration in 2p+1 schedule

Biological: PCV10

40% dose PCV10 (2p+1 schedule)

EXPERIMENTAL

Fractional (40%) dose PCV10 administration in 2p+1 schedule

Biological: PCV10

20% dose PCV10 (2p+1 schedule)

EXPERIMENTAL

Fractional (20%) dose PCV10 administration in 2p+1 schedule

Biological: PCV10

Full dose PCV10 (3p+0 schedule)

ACTIVE COMPARATOR

The current vaccine (PCV10) and schedule (3p+0) in use in the Kenyan routine immunisation programme as an additional comparison arm.

Biological: PCV10

Interventions

PCV10 BIOLOGICAL

Experimental arms will receive a lower dose of the intervention than the marketed dose.

Also known as: Synflorix (GlaxoSmithKline plc.), 10-valent pneumococcal conjugate vaccine

20% dose PCV10 (2p+1 schedule); 40% dose PCV10 (2p+1 schedule); Full dose PCV10 (2p+1 schedule); Full dose PCV10 (3p+0 schedule)

PCV13 BIOLOGICAL

Experimental arms will receive a lower dose of the intervention than the marketed dose.

Also known as: Prevnar 13 (Pfizer Inc.), 13-valent pneumococcal conjugate vaccine, Prevnar13

20% dose PCV13 (2p+1 schedule); 40% dose PCV13 (2p+1 schedule); Full dose PCV13 (2p+1 schedule)

Eligibility Criteria

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

You may qualify if:

• Healthy infants aged 6-8 weeks of age (HIV positive or negative but with no symptoms of current clinical immunosuppression i.e. HIV infection at WHO clinical stage 1);
• Parents are willing to provide informed consent for their child to participate in the study
• Parents and infant are likely to remain in the study area until the infant is 18 months of age and comply with study requirements including the requirement to return to the same health facility to obtain all other childhood vaccines.

You may not qualify if:

• Infants \>8 weeks of age at time of enrolment
• Signs or symptoms of immunosuppression or HIV infection clinical stage 2 or above.
• Acute illness (e.g. febrile disease) on the day of vaccination
• Contraindications precluding vaccination (e.g. hypersensitivity to any component of the vaccine, including diphtheria toxoid)
• Previous PCV vaccination
• Family are planning to migrate out of the study areas before the end of the study follow-up
• Family are planning to obtain the subsequent vaccine doses of the routine immunisation schedule elsewhere and therefore their child may receive a full dose under the routine vaccination programme.

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• University College, London: collaborator
• KEMRI-Wellcome Trust Collaborative Research Program: collaborator
• Bill and Melinda Gates Foundation: collaborator
• National Institute of Health Research (NIHR) Mucosal Pathogens Research Unit (MPRU): collaborator
• Wellcome Trust: collaborator

Study Sites (1)

KEMRI Wellcome Trust Research Programme

Kilifi, Kenya

Location

Related Publications (1)

• Gallagher KE, Lucinde R, Bottomley C, Kaniu M, Suaad B, Mutahi M, Mwalekwa L, Ragab S, Twi-Yeboah L, Berkley JA, Hamaluba M, Karani A, Shangala J, Otiende M, Gardiner E, Mugo D, Smith PG, Tabu C, Were F, Goldblatt D, Scott JAG. Fractional Doses of Pneumococcal Conjugate Vaccine - A Noninferiority Trial. N Engl J Med. 2024 Nov 28;391(21):2003-2013. doi: 10.1056/NEJMoa2314620. Epub 2024 Sep 26.

  PMID: 39330966 DERIVED

MeSH Terms

Conditions

Pneumococcal Infections

Interventions

10-valent pneumococcal conjugate vaccine; PHiD-CV vaccine; 13-valent pneumococcal vaccine

Condition Hierarchy (Ancestors)

Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• J. Anthony G Scott, DTMH FMedSci

  London School of Hygiene & Tropical Medicine, Keppel Street, London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, parents of participants and all of the study team apart from the vaccinator will be masked with respect to the infant's allocation to a trial arm between A-F. If randomly allocated to trial arm G, parents and study personnel will be unmasked due to the necessity for trial arm G to receive a different vaccine schedule compared to trial arms A-F. It is thought that this unmasking will have minimal impact on retention, follow up and outcome assessment across the trial arms for primary and secondary outcomes.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomised to one of seven groups for the duration of the study: A. Full dose PCV13 vaccination in a 2p+1 schedule; B. 40% fractional dose PCV13 vaccination in a 2p+1 schedule; C. 20% fractional dose PCV13 vaccination in a 2p+1 schedule; D. Full dose PCV10 vaccination in a 2p+1 schedule; E. 40% fractional dose PCV10 vaccination in a 2p+1 schedule; F. 20% fractional dose PCV10 vaccination in a 2p+1 schedule; G. Full dose PCV10 vaccination in a 3p+0 schedule.

Study Record Dates

• First Submitted: March 29, 2018
• First Posted: November 21, 2018
• Study Start: March 21, 2019
• Primary Completion: September 30, 2022
• Study Completion: November 1, 2024
• Last Updated: November 12, 2024

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: After the primary analyses of the trial are published
• Access Criteria: Upon reasonable request with pre-specified hypothesis

Locations

KE (1)