Fully Liquid MenACWY-CRM Vaccine: Results from an Integrated Safety Analysis

Puneet Vir Singh, Paola Tiberi, Gabriele Filippo Di Domenico, Valerio Romolini, Thembile Mzolo, Marco Costantini, Tauseefullah Akhund, Venere Basile, Maria Lattanzi, Michele Pellegrini, Puneet Vir Singh, Paola Tiberi, Gabriele Filippo Di Domenico, Valerio Romolini, Thembile Mzolo, Marco Costantini, Tauseefullah Akhund, Venere Basile, Maria Lattanzi, Michele Pellegrini

Abstract

Introduction: The currently licensed quadrivalent MenACWY-CRM conjugate vaccine presentation consists of two vials (lyophilized MenA and liquid MenCWY) to be reconstituted before injection. A new fully liquid, single-vial formulation has been developed to simplify administration and prevent reconstitution errors. We present pooled safety data from two randomized, controlled, observer-blind phase 2b clinical trials, in which the fully liquid presentation was compared with the licensed presentation.

Methods: This is a post hoc analysis of two studies, in which safety data from participants aged 10-40 years who received one dose of either liquid MenACWY-CRM (1337 participants; MenACWY liquid group) or licensed MenACWY-CRM (1332 participants; MenACWY licensed group) were pooled. Frequencies were calculated for solicited adverse events (AEs) during 7 days post-vaccination and unsolicited AEs, including medically attended AEs and serious AEs (SAEs), during the 6-month safety follow-up period. Analysis results are presented by vaccine group, overall and by age category (10-17 and 18-40 years).

Results: Overall, AEs solicited for collection during the first 7 days after vaccination were reported by similar percentages of participants (69.2%, MenACWY liquid; 68.2%, MenACWY licensed), and were generally mild/moderate in intensity. Solicited local AEs were reported by 46.0% of the MenACWY liquid group and 43.5% of the MenACWY licensed group and solicited systemic AEs by 55.2 and 54.1%, respectively. During the 6-month post-vaccination period, unsolicited AEs were reported by 32.2 and 31.2% of the MenACWY liquid group and MenACWY licensed group, respectively, and medically attended AEs by 18.6 and 17.3%, respectively. Overall, 14 participants in each group (1.0 and 1.1%, respectively) reported SAEs, none of which was considered vaccine-related by the investigator. The safety profiles of both MenACWY-CRM presentations were similar for each age group and overall.

Conclusions: This pooled analysis shows the safety profile of fully liquid MenACWY-CRM is comparable with that of the currently licensed vaccine presentation.

Clinical trial registration: ClinicalTrials.gov Identifiers: NCT03652610 (August 29, 2018), NCT03433482 (14 February 2018).

Conflict of interest statement

PVS, PT, GFDD, VR, TM, MC, VB, ML, and MP are employed by GSK. TA was employed by GSK when the analyses were conducted. PVS, TA, VB, ML, and MP hold shares in GSK. PVS, PT, GFDD, VR, TM, MC, TA, VB, ML, and MP declare no other financial and non-financial relationships and activities.

© 2022. GSK.

Figures

Fig. 1
Fig. 1
Demographic characteristics of participants included in the pooled analysis of safety using data from two phase 2b clinical studies in which participants received a single dose of either the fully liquid investigational presentation (MenACWY liquid) or the licensed presentation (MenACWY licensed) of MenACWY-CRM vaccine. aOne participant was aged 44 years at enrolment and was excluded from the per-protocol immunogenicity analysis [12] but was included in the analysis of safety. N = number of participants who received either MenACWY liquid or MenACWY licensed vaccine; SD = standard deviation

References

    1. Wang B, Santoreneos R, Giles L, Haji Ali Afzali H, Marshall H. Case fatality rates of invasive meningococcal disease by serogroup and age: a systematic review and meta-analysis. Vaccine. 2019;37(21):2768–2782. doi: 10.1016/j.vaccine.2019.04.020.
    1. Olbrich KJ, Müller D, Schumacher S, Beck E, Meszaros K, Koerber F. Systematic review of invasive meningococcal disease: sequelae and quality of life impact on patients and their caregivers. Infect Dis Ther. 2018;7(4):421–438. doi: 10.1007/s40121-018-0213-2.
    1. Parikh S, Campbell H, Bettinger JA, Harrison LH, Marshall HS, Martinon-Torres F, et al. The everchanging epidemiology of meningococcal disease worldwide and the potential for prevention through vaccination. J Infect. 2020;81:483–498. doi: 10.1016/j.jinf.2020.05.079.
    1. Pizza M, Bekkat-Berkani R, Rappuoli R. Vaccines against meningococcal diseases. Microorganisms. 2020 doi: 10.3390/microorganisms8101521.
    1. Martinón-Torres F, Taha MK, Knuf M, Abbing-Karahagopian V, Pellegrini M, Bekkat-Berkani R, et al. Evolving strategies for meningococcal vaccination in Europe: overview and key determinants for current and future considerations. Pathog Glob Health. 2021 doi: 10.1080/20477724.2021.1972663.
    1. Keshavan P, Pellegrini M, Vadivelu-Pechai K, Nissen M. An update of clinical experience with the quadrivalent meningococcal ACWY-CRM conjugate vaccine. Expert Rev Vaccines. 2018;17(10):865–880. doi: 10.1080/14760584.2018.1521280.
    1. Ruiz Garcia Y, Abitbol V, Pellegrini M, Bekkat-Berkani R, Soumahoro L. A decade of fighting invasive meningococcal disease: a narrative review of clinical and real-world experience with the MenACWY-CRM conjugate vaccine. Infect Dis Ther. 2021 doi: 10.1007/s40121-021-00519-2.
    1. Bröker M, Dull PM, Rappuoli R, Costantino P. Chemistry of a new investigational quadrivalent meningococcal conjugate vaccine that is immunogenic at all ages. Vaccine. 2009;27(41):5574–5580. doi: 10.1016/j.vaccine.2009.07.036.
    1. Berti F, Romano MR, Micoli F, Pinto V, Cappelletti E, Gavini M, et al. Relative stability of meningococcal serogroup A and X polysaccharides. Vaccine. 2012;30(45):6409–6415. doi: 10.1016/j.vaccine.2012.08.021.
    1. Beresford NJ, Martino A, Feavers IM, Corbel MJ, Bai X, Borrow R, et al. Quality, immunogenicity and stability of meningococcal serogroup ACWY-CRM197, DT and TT glycoconjugate vaccines. Vaccine. 2017;35(28):3598–3606. doi: 10.1016/j.vaccine.2017.03.066.
    1. Su JR, Miller ER, Duffy J, Baer BM, Cano MV. Notes from the field: administration error involving a meningococcal conjugate vaccine–United States, March 1, 2010–September 22. MMWR Morb Mortal Wkly Rep. 2016;65(6):161–162. doi: 10.15585/mmwr.mm6506a4.
    1. Vandermeulen C, Leroux-Roels I, Vandeleur J, Staniscia T, Girard G, Ferguson M, et al. A new fully liquid presentation of MenACWY-CRM conjugate vaccine: results from a multicentre, randomised, controlled, observer-blind study. Vaccine. 2021;39(45):6628–6636. doi: 10.1016/j.vaccine.2021.09.068.
    1. Díez-Domingo J, Tinoco JC, Poder A, Dinleyici EC, Nell H, Salamanca de la Cueva I, et al. 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. Hum Vaccin Immunother. 2022;18(1):1981085. doi: 10.1080/21645515.2021.1981085.
    1. Bröker M, Cooper B, Detora LM, Stoddard JJ. Critical appraisal of a quadrivalent CRM197 conjugate vaccine against meningococcal serogroups A, C W-135 and Y (Menveo) in the context of treatment and prevention of invasive disease. Infect Drug Resist. 2011;4:137–147. doi: 10.2147/idr.s12716.
    1. Lalwani S, Agarkhedkar S, Gogtay N, Palkar S, Agarkhedkar S, Thatte U, et al. Safety and immunogenicity of an investigational meningococcal ACWY conjugate vaccine (MenACWY-CRM) in healthy Indian subjects aged 2 to 75 years. Int J Infect Dis. 2015;38:36–42. doi: 10.1016/j.ijid.2015.07.003.
    1. Jackson LA, Baxter R, Reisinger K, Karsten A, Shah J, Bedell L, et al. Phase III comparison of an investigational quadrivalent meningococcal conjugate vaccine with the licensed meningococcal ACWY conjugate vaccine in adolescents. Clin Infect Dis. 2009;49(1):e1–10. doi: 10.1086/599117.
    1. Chang LJ, Hedrick J, Christensen S, Pan J, Jordanov E, Dhingra MS. A Phase II, randomized, immunogenicity and safety study of a quadrivalent meningococcal conjugate vaccine, MenACYW-TT, in healthy adolescents in the United States. Vaccine. 2020;38(19):3560–3569. doi: 10.1016/j.vaccine.2020.03.017.

Source: PubMed

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