Immunological non-inferiority of a new fully liquid presentation of the MenACWY-CRM vaccine to the licensed vaccine: results from a randomized, controlled, observer-blind study in adolescents and young adults

ABSTRACT

A fully liquid MenACWY-CRM vaccine presentation has been developed, modifying the meningococcal serogroup A (MenA) component from lyophilized to liquid. The safety and immunogenicity of the liquid presentation at the end of the intended shelf-life (aged for 24 or 30 months) were compared to the licensed lyophilized/liquid presentation. This multicenter, randomized (1:1), observer-blind, phase 2b study (NCT03433482) enrolled adolescents and young adults (age 10–40 years). In part 1, 844 participants received one dose of liquid presentation stored for approximately 24 months or licensed presentation. In part 2, 846 participants received one dose of liquid presentation stored for approximately 30 months or licensed presentation. After storage, the MenA free saccharide (FS) level was approximately 25% and O-acetylation was approximately 45%. The primary objective was to demonstrate non-inferiority of the liquid presentation to licensed presentation, as measured by human serum bactericidal assay (hSBA) geometric mean titers (GMTs) against MenA, 1-month post-vaccination. Immune responses against each vaccine serogroup were similar between groups. Between-group ratios of hSBA GMTs for MenA were 1.21 (part 1) and 1.11 (part 2), with two-sided 95% confidence interval lower limits (0.94 and 0.87, respectively) greater than the prespecified non-inferiority margin (0.5), thus meeting the primary study objective. No safety concerns were identified. Despite reduced O-acetylation of MenA and increased FS content, serogroup-specific immune responses induced by the fully liquid presentation were similar to those induced by the licensed MenACWY-CRM vaccine, with non-inferior anti-MenA responses. The safety profiles of the vaccine presentations were similar.

KEYWORDS:

• MenACWY-CRM
• meningococcal serogroup A
• human serum bactericidal assay
• non-inferiority
• adolescents

Acknowledgments

The authors thank all participants, parents, and the clinical teams and investigators involved in this study, especially Cristiano Zerbini, Satu Kokko, Asmik Asatryan, Jose Garcia-Sicilia, Marta Aldea Novo, Merce Perez Vera, Benita Ukkonen, Freddy Eliaschewitz, Dmitriy Lioznov, Phu My Tran, Anitta Ahonen and Pinar Yildiz. The authors thank the GSK study team, especially Bertrand De Wergifosse, Pavitra Keshavan, Silvia Barbi, Frans Corthals, Sara Nannizzi, and Joke Vandewalle for their contributions to the study, as well as Lamine Soumahoro and Lucy Hitchcock for critical review of this manuscript. The authors also thank Business & Decision Life Sciences platform for editorial assistance, manuscript coordination and writing support, on behalf of GSK. Joanne Knowles (independent medical writer, on behalf of Business & Decision Life Sciences) provided medical writing support. Bruno Dumont coordinated the manuscript development and editorial support.

Additional information

Menveo is a trademark owned by or licensed to the GSK group of companies.

All authors participated in the design or implementation of the study and were involved in the analysis and interpretation of the results and the development of this article. All authors had full access to the data and gave final approval before submission.

Anonymized individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com.

Disclosure statement

T.A., V.R., M.C., T.M., B.K., I.L., M.L., E.F., V.B., M.A., J.-A.G.-M., P.T., K.N., and M.P. are employed by the GSK group of companies. T.A., M.L., E.F., V.B., M.A., and M.P. hold shares in the GSK group of companies. J.D.-D. reports payments from the GSK group of companies and Sanofi Pasteur to his institution, outside the submitted work. E.C.D. reports payments from the GSK group of companies to his institution for the conduct of the study, and Sanofi Pasteur and Pfizer, outside the submitted work. I.S.C. reports payments from the GSK group of companies, Sanofi Pasteur, MSD, and Pfizer, outside the submitted work. E.D.M. Jr reports payments from the GSK group of companies to his institution for the conduct of the study. J.D.-D., E.C.D., I.S.C., E.D.M. Jr, T.A., V.R., M.C., T.M., B.K., I.L., M.L., E.F., V.B., M.A., J.-A.G.-M., P.T., K.N., and M.P. declare no other financial and non-financial relationships and activities. J.C.T., A.P., H.N., I.S.C., T.I., K.A., K.L., Y.K. and C.E.M.P. declare no financial and non-financial relationships and activities and no conflicts of interest.

Correction Statement

Trial registration: https://clinicaltrials.gov/; NCT03433482, registered February 14, 2018.This article has been corrected with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This study was funded by GlaxoSmithKline Biologicals SA, which was involved in all stages of study conduct, including analysis of the data. GlaxoSmithKline Biologicals SA also took in charge all costs associated with the development and publication of this manuscript.