A Phase 3, Randomized, Partially-Blind, Clinical Trial to Evaluate the Non-Inferiority of a 12-Valent Pneumococcal Conjugate Vaccine in Healthy Children in Brazil, Compared to 10- and 13-Valent Pneumococcal Conjugate Vaccines

Maria de Lourdes de Sousa Maia, MD0 sites2,400 target enrollmentAugust 28, 2023

Overview

Brief Summary

The purpose of this phase III study is to demonstrate immunologic non-inferiority in terms of proportion of individuals with antibody concentration ≥0.2 µg/mL (by modified 22F-inhibition enzyme-linked immunosorbent assay, ELISA) or in terms of ELISA geometric mean concentrations (GMC) of serotype-specific IgG, of 12-valent pneumococcal polysaccharide conjugate vaccine (12Pn-PD-DiT-CRM, hereby indicated as PCV12), containing the serotypes 1, 4, 5, 6B, 7F, 9V, 14, and 23F conjugated with non-typeable Haemophilus influenzae protein D, 19F conjugated with TD, 18C conjugated with TT, and 6A and 19A conjugated with CRM197, and to assess its safety in the population of infants vaccinated from 2 months of age with a primary regimen of 2 or 3 doses plus a booster administered at one year of life.

Detailed Description

The purpose of this phase III study is to demonstrate immunologic non-inferiority in terms of proportion of individuals with antibody concentration ≥0.2 µg/mL (by modified 22F-inhibition enzyme-linked immunosorbent assay, ELISA) or in terms of ELISA geometric mean concentrations (GMC) of serotype-specific IgG, of 12-valent pneumococcal polysaccharide conjugate vaccine (12Pn-PD-DiT-CRM, hereby indicated as PCV12), containing the serotypes 1, 4, 5, 6B, 7F, 9V, 14, and 23F conjugated with non-typeable Haemophilus influenzae protein D, 19F conjugated with TD, 18C conjugated with TT, and 6A and 19A conjugated with CRM197, and to assess its safety in the population of infants vaccinated from 2 months of age with a primary regimen of 2 or 3 doses plus a booster administered at one year of life. Hence, this study will provide non-inferiority evidence for possible approval of a new pneumococcal vaccine in Brazil and its eventual inclusion in the national immunization program (PNI). PCV12 will be produced in national facilities, after transfer of technology to Bio-Manguinhos/Fiocruz, thus ensuring continuous provision to the public healthcare system (SUS). This study is designed to demonstrate the immunologic non-inferiority of the PCV12 for each one of the 12 vaccine pneumococcal serotypes, when compared to the licensed vaccines GSK Synflorix® (PCV10) and Pfizer's/Wyeth's Prevenar 13® (PCV13). PCV10 will be used for the comparison of the immune response to the 10 common serotypes. PCV13 or the least immunogenic serotype of PCV10 will be used for the comparison of the immune response to the two additional pneumococcal serotypes 19A and/or 6A conjugated to CRM197. The non-inferiority of PCV12 will be evaluated in the two schedules recommended in Brazil, the 2+1 scheme (followed by PNI) or the 3+1 scheme (the reference schedule when evaluating new vaccines).

Registry

clinicaltrials.gov

Start Date

August 28, 2023

End Date

January 28, 2025

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Maria de Lourdes de Sousa Maia, MD

Responsible Party

Sponsor Investigator

Principal Investigator

Maria de Lourdes de Sousa Maia, MD

Sponsor

The Immunobiological Technology Institute (Bio-Manguinhos) / Oswaldo Cruz Foundation (Fiocruz)

Eligibility Criteria

Inclusion Criteria

•Male or female subjects, 6-12 weeks of age, inclusive, at the time of the first vaccination.
•Healthy subjects as established by medical history and clinical examination before entering into the study.
•Subjects who the investigator believes that parent(s)/ Legally Acceptable Representative(s) \[LAR(s)\] can and will comply with the requirements of the protocol, including:
•willing to provide name, address, and telephone number for contact if necessary (e.g., in case of missing a scheduled visit)
•available for follow-up throughout the study period
•capable to complete the forms for registration of signs and symptoms at home.
•Parent(s)/LAR(s) are able to understand and sign the informed consent form.

Exclusion Criteria

•Preterm infants (gestation \<36 weeks) or with low birth weight (\<2000g).
•Use of any investigational or non-registered product other than the study vaccines and allowed co-administered vaccines as outlined in section 3.4.
•during the entire study period. Any other vaccine administration must be discussed and approved by the medical monitor.
•Medical history of culture- or PCR-confirmed invasive disease caused by S. pneumoniae.
•Coagulation problems.
•Chronic administration (more than 14 days in total) of corticosteroids, immunosuppressants or other immune-modifying drugs (except palivizumab) since birth or planned use during the study.
•Administration of immunoglobulins and/or blood products since birth or planned use during the study period.
•Participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product.
•Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
•History of any reaction or hypersensitivity likely to be exacerbated by any component of the study vaccine.

Outcomes

Primary Outcomes

The immunological non-inferiority of pneumococcal vaccine 12 in relation to pneumococcal vaccine 10 and 13.

Time Frame: 5 months

Proportion of subjects with serotype-specific pneumococcal IgG antibody concentration ≥0.20 µg/mL after primary vaccination.Geometric mean concentrations of serotype-specific pneumococcal IgG antibody after primary vaccination.