An indirect treatment comparison (ITC) and matching-adjusted indirect comparison (MAIC) between a 15-valent (V114) and a 20-valent (PCV20) pneumococcal conjugate vaccine among healthy infants

ABSTRACT

Objectives

Immunogenicity between 15-valent V114 (PCV15) and 20-valent PCV20 pneumococcal conjugate vaccines in healthy infants is compared in an indirect treatment comparison and matching-adjusted indirect comparison. Hypotheses: immunogenicity of V114 is non-inferior to PCV20 for all PCV13 serotypes, and superior to PCV20 for serotype 3 based on lower bound margins.

Methods

Two phase 3 pivotal studies on 3 + 1 pediatric vaccination schedule at age 2, 4, 6, and 12–15 months compared V114 (N = 858) to PCV13 (N = 856) and PCV20 (N = 1001) to PCV13 (N = 987). Infant’s age and race in V114 study were matched to those in PCV20 study. Primary endpoints were serotype-specific Immunoglobulin G (IgG) response rate difference (RRD) 30 days post-dose (PD)3; IgG geometric mean concentration (GMC) ratios 30 days PD3 and PD4.

Results

V114 was non-inferior ($\mathrm{m}\mathrm{a}\mathrm{r}\mathrm{g}\mathrm{i}{\mathrm{n}}_{RRD}$>-10%-point; $\mathrm{m}\mathrm{a}\mathrm{r}\mathrm{g}\mathrm{i}{\mathrm{n}}_{GMCratio}$ >0.5) to PCV20 (p-value <0.001) for all endpoints. V114 was superior ($\mathrm{m}\mathrm{a}\mathrm{r}\mathrm{g}\mathrm{i}{\mathrm{n}}_{RRD}$ >0%-point; $\mathrm{m}\mathrm{a}\mathrm{r}\mathrm{g}\mathrm{i}{\mathrm{n}}_{GMCratio}$ >1.2) to PCV20 (p-value <0.001) for serotype 3: RRD was 34.5% (95%CI 27.9%-41.1%) PD3, and IgG GMC ratios were 2.39 (95%CI 2.12–2.68) PD3 and 2.15 (95%CI 1.90–2.41) PD4.

Conclusion

Immune response to V114 administered in a 3 + 1 schedule in healthy infants was considered non-inferior to PCV20 for all 13 PCV13 serotypes and superior for serotype 3 PD3 and PD4.

Clinical trial registration

www.clinicaltrials.gov identifiers NCT03893448, NCT04382326

KEYWORDS:

• MAIC
• indirect treatment comparison
• pneumococcal conjugate vaccine
• immunoglobulin G
• immunogenicity
• PCV15
• GMC ratio
• IgG response rate

Declaration of interest

All authors are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A., and may hold stock in Merck & Co., Inc., Rahway, NJ, U.S.A.. All authors declare no non-financial competing interests. The funder had a role in the conceptualization, design, data collection, analysis, decision to publish, and preparation of the manuscript.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

All authors (1) substantially contributed to the conception and design of the review of the article and interpreting the relevant literature and (2) been involved in the writing the article or revised it for intellectual content.

All authors critically reviewed the manuscript and approved the final version of the manuscript.

Ethical approval

No ethical approval was required since the research presented in this manuscript was based on secondary post-hoc analyses, and individual-level data on V114 used are internal data to the Company and therefore do not require further permission. The data on PCV20 are aggregate data freely available in public domain, and therefore do not require permission to use.

Acknowledgments

This research was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and conducted by its employees. Therefore, the funder had a role in the conceptualization, study design, data collection, analysis and interpretation of data, decision to publish, and preparation of this manuscript. The phase 3 studies of which data were used for the analyses were conducted with financial support from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (the V114 phase 3 study) for V114 and Pfizer, Inc., New York, NY, USA (the PCV20 phase 3 study) for PCV20. The authors would like to thank Merck & Co., Inc., Rahway, NJ, USA for providing the V114 study data, and Pfizer for making their PCV20 phase 3 study data used in our analyses publicly available. The authors would like to thank the following people at Merck & Co., Inc., Rahway, NJ, USA for providing input into the work presented in this manuscript: Robert Lupinacci for his help with the study design and statistical analyses, Dr. Shrita Patel for providing technical input into the study design and conducting the clinical feasibility assessment of the safety analysis, and Michael Allie for technical support of the analysis production with his statistical programming expertise. Professional medical writing support was provided by Dr. Michel D. Wissing and Holly R. Tomlin, Certara Synchrogenix.

Data availability statement

Summary/aggregate data from the PCV20 study were used for this analysis and are publicly available online [18, 21-22]; the authors of this study do not own these data. Data from the V114 phase 3 study used in this analysis may be made available to qualified researchers upon reasonable request from the corresponding author and/or Merck & Co., Inc., Rahway, NJ, U.S.A. (Data Access mailbox).

Code availability

The programming codes for the analysis in this study are not publicly available but parts that do not contain proprietary information may be made available to qualified researchers on reasonable request from the corresponding author.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14760584.2023.2270039.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

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