A phase 3 randomized, open-label study evaluating the immunogenicity and safety of concomitant and staggered administration of a live, pentavalent rotavirus vaccine and an inactivated poliomyelitis vaccine in healthy infants in China

ABSTRACT

This open-label, randomized, phase 3 study in China (V260-074; NCT04481191) evaluated the immunogenicity and safety of concomitant and staggered administration of three doses of an oral, live, pentavalent rotavirus vaccine (RV5) and three doses of an intramuscular, inactivated poliomyelitis vaccine (IPV) in 400 healthy infants. The primary objective was the non-inferiority of neutralizing antibody (nAb) responses in the concomitant- versus the staggered-use groups. Antibody responses were measured at baseline and 1-month post-dose 3 (PD3). Parents/legal guardians recorded adverse events for 30 or 15 d after study vaccinations in the concomitant-use or staggered-use groups, respectively. At PD3, >98% of participants seroconverted to all three poliovirus types, and the primary objective was met as lower bounds of the two-sided 95% CI for between-group difference in nAb seroconversion percentages ranged from − 4.3% to − 1.6%, for all poliovirus types, p < .001. At PD3, geometric mean titers (GMTs) of nAb responses to poliovirus types 1, 2, and 3 in the concomitant-use group and the staggered-use group were comparable; 100% of participants had nAb titers ≥1:8 and ≥1:64 for all poliovirus types. Anti-rotavirus serotype-specific IgA GMTs and participants with ≥3-fold rise in postvaccination titers from baseline were comparable between groups. Administration of RV5 and IPV was well tolerated with comparable safety profiles in both groups. The immunogenicity of IPV in the concomitant-use group was non-inferior to the staggered-use group and RV5 was immunogenic in both groups. No safety concerns were identified. These data support the concomitant use of RV5 and IPV in healthy Chinese infants.

KEYWORDS:

• Poliomyelitis
• gastroenteritis
• immunogenicity
• safety
• concomitant
• pentavalent rotavirus vaccine
• inactivated polio vaccine

Acknowledgments

The authors thank all principal investigators for their contributions to the study. Medical writing and editorial support was provided by Toinette Labuschagné, MSc, and Andrea Humphries, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure statement

Zhifang Ying, Yan Liu, Yong Zhang, and Changgui Li are all current employees of the National Institutes for Food and Drug Control (NIFDC), which is responsible for the immunogenicity sample testing. Guixiu Liu, Weiwei Zhao, Rong Fu, Qiong Shou, Minghuan Zheng, and Xueyan Liao are current or former employees of MSD Research and Development (China) Co., Ltd., Beijing, China, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may own stock and/or options in Merck & Co., Inc., Rahway, NJ, USA. Yingmei Tu, Jon Stek, and Jonathan Hartzel are current or former employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may own stock and/or options in Merck & Co., Inc., Rahway, NJ, USA. Shaomin Chen, Yuan Li, Yebin Yu, Meilian Huang, Zhuhang Huang, Zhiqiang Ou, Yuyi Liao, and Jikai Zhang have no conflicts to disclose.

Author contributions

Shaomin Chen, Zhifang Ying, Yan Liu, Yuan Li, Yebin Yu, Meilian Huang, Zhuhang Huang, Zhiqiang Ou, Yuyi Liao, Yong Zhang, Guixiu Liu, Weiwei Zhao, Rong Fu, Qiong Shou, Minghuan Zheng, Xueyan Liao, Changgui Li, and Jikai Zhang contributed to the concept and design of the work. Shaomin Chen, Zhifang Ying, Yan Liu, Yuan Li, Yebin Yu, Meilian Huang, Zhuhang Huang, Zhiqiang Ou, Yuyi Liao, Yong Zhang, Guixiu Liu, Weiwei Zhao, Rong Fu, Qiong Shou, Minghuan Zheng, Xueyan Liao, Changgui Li, and Jikai Zhang contributed to the data acquisition. Shaomin Chen, Zhifang Ying, Yan Liu, Yuan Li, Yebin Yu, Meilian Huang, Zhuhang Huang, Zhiqiang Ou, Yuyi Liao, Yong Zhang, Guixiu Liu, Weiwei Zhao, Rong Fu, Qiong Shou, Minghuan Zheng, Xueyan Liao, and Jikai Zhang contributed to data analysis. Shaomin Chen, Zhifang Ying, Yan Liu, Yuan Li, Yebin Yu, Meilian Huang, Zhuhang Huang, Zhiqiang Ou, Yuyi Liao, Yong Zhang, Guixiu Liu, Weiwei Zhao, Rong Fu, Qiong Shou, Minghuan Zheng, Xueyan Liao, Yingmei Tu, Jon Stek, Jonathan Hartzel, Changgui Li, and Jikai Zhang contributed to interpretation of data for the manuscript. Shaomin Chen, Zhifang Ying, Yan Liu, Yuan Li, Yebin Yu, Meilian Huang, Zhuhang Huang, Zhiqiang Ou, Yuyi Liao, Yong Zhang, Guixiu Liu, Weiwei Zhao, Rong Fu, Qiong Shou, Minghuan Zheng, Xueyan Liao, Yingmei Tu, Jon Stek, Jonathan Hartzel, Changgui Li, and Jikai Zhang drafted the manuscript. Shaomin Chen, Zhifang Ying, Yan Liu, Yuan Li, Yebin Yu, Meilian Huang, Zhuhang Huang, Zhiqiang Ou, Yuyi Liao, Yong Zhang, Guixiu Liu, Weiwei Zhao, Rong Fu, Qiong Shou, Minghuan Zheng, Xueyan Liao, Yingmei Tu, Jon Stek, Jonathan Hartzel, Changgui Li, and Jikai Zhang revisited the manuscript critically for important intellectual content. All authors approved the final version of the manuscript and are accountable for all aspects of the work.

Data availability statement

The data sharing policy, including restrictions, of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA is available at http://engagezone.msd.com/ds_documentation.php. Requests for access to the clinical study data can be submitted through the Engage Zone site or via e-mail to Data Access mailbox.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2024.2324538.

Additional information

Funding

This study was sponsored by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.