Safety and immunogenicity of a new 13-valent pneumococcal conjugate vaccine versus a licensed 7-valent pneumococcal conjugate vaccine: a study protocol of a randomised non-inferiority trial in China

Jing Jing Chen, Lin Yuan, Zhen Huang, Nian Min Shi, Yu Liang Zhao, Sheng Li Xia, Guo Hua Li, Rong Cheng Li, Yan Ping Li, Shu Yuan Yang, Jie Lai Xia, Jing Jing Chen, Lin Yuan, Zhen Huang, Nian Min Shi, Yu Liang Zhao, Sheng Li Xia, Guo Hua Li, Rong Cheng Li, Yan Ping Li, Shu Yuan Yang, Jie Lai Xia

Abstract

Introduction: The invasive pneumococcal diseases (IPDs) caused by Streptococcus pneumoniae pose an enormous threat to children under 5 years of age. However, routine use of pneumococcal conjugate vaccines could aid in reducing the incidence of IPDs. The purpose of this clinical trial is to assess the non-inferiority of the investigational 13-valent pneumococcal conjugate vaccine (PCV13) to the currently licensed 7-valent pneumococcal conjugate vaccine (PCV7).

Methods and analysis: 1040 infants will receive a three-dose series of either PCV13 or PCV7 at ages 3, 4 and 5 months, respectively, and a booster dose at 12-15 months. Primary end points are the percentage of participants reaching a serotype-specific IgG concentration of ≥0.35 µg/mL and the IgG antibody geometric mean concentrations (GMCs) measured 30 days after the primary immunisation. Secondary end points include the percentage of vaccine recipients reaching a serotype-specific IgG concentration threshold of 1.0 µg/mL, the percentage of participants reaching the pneumococcal opsonophagocytic assay (OPA) titre threshold of 1:8, and the geometric mean titres (GMTs) of OPA measured 30 days after primary and booster doses. The number of standard IgG responders and IgG GMCs measured 30 days after the booster immunisation will also be determined. To evaluate differences between two groups, the sequential testing of the non-inferiority of PCV13 for the seven common serotypes and its effectiveness in treating the six additional serotypes will be performed.

Ethics and dissemination: Ethics approvals have been granted by the Ethics Committees at the three provinces involved in this study: Shanxi, Henan and Hebei. The trial will be reported in accordance with the CONSORT guidance.

Trial registration number: NCT02736240.

Keywords: Non-inferiority; Pneumococcal conjugate vaccine; Sequential test.

Conflict of interest statement

We have read and understood BMJ policy on declaration of interests and declare the following interests: This trial is sponsored by Walvax Biotechnology Co. Walvax, as the sponsor, is responsible for organising and managing the study to support the prelicensing evaluation of the investigational PCV13. The new PCV13 was researched and developed by Walvax and manufactured by an affiliate of Walvax. JJC, LY, ZH and SYY work at Walvax and belong to the clinical research team of PCV13.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Figures

Figure 1
Figure 1
The study flow diagram.
Figure 2
Figure 2
The sequential test flow chart. GMC, geometric mean concentrations; PCV13, 13-valent pneumococcal conjugate vaccine; PCV7, 7-valent pneumococcal conjugate vaccine.

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