632. Clinical Experience with a New Fully Liquid Presentation of the MenACWY-CRM Vaccine. Results from Two Multicenter, Randomized, Controlled, Observer-Blind, Phase 2b Studies
Authors: Díez-Domingo Javier , Vandermeulen Corinne , Akhund Tauseefullah , Costantini Marco , Singh Puneet Vir , Basile Venere , Fragapane Elena , Lattanzi Maria , Pellegrini Michele 
Published: December 2021

Abstract

Background
Currently, licensed MenACWY-CRM conjugate vaccine presentation (Lyo/Liq) consists of two vials (lyophilized MenA, liquid MenCWY) to be reconstituted before injection. A new, fully liquid, single vial formulation has been developed and evaluated in two clinical studies in adolescents and adults aimed at demonstrating immunological non-inferiority of the liquid presentation for MenA.

Methods
Overall, 1337 subjects, 10 to 40 years of age (y), were exposed to a single 0.5 mL intramuscular dose of MenACWY Liquid and 1332 to MenACWY-CRM(Lyo/Liq). MenACWY-CRM Liquid was aged before administration, to test the vaccine immunogenicity at the end of the intended shelf-life and establish release and end of shelf life specifications. MenACWY-CRM(Lyo/Liq) was used as comparator and was not aged. In study 1 (NCT03652610), the Liquid vaccine underwent an ageing process under controlled conditions to reach ~30% MenA free saccharide (FS). In study 2 (NCT03433482), the Liquid vaccine was naturally aged at 2–8°C for approximately 24 and 30 months. Primary immunogenicity objective in both studies was non-inferiority of MenACWY-CRM liquid to licensed vaccine, as measured by human serum bactericidal assay (hSBA) geometric mean titers (GMTs) against MenA, 1-month post-vaccination.

Results
In both studies, for each between-group ratio of MenA hSBA GMTs, lower limits of the 95% confidence intervals (CIs) were greater than the prespecified non-inferiority margin (0.5), thus meeting the non-inferiority immunogenicity objective. Irrespectively of the vaccine presentation tested, over 82% of participants achieved MenA hSBA titers ≥ 8 in study 1 and at least 92% in study 2. The immunogenicity of MenACWY-CRM Liquid was similar to that of MenACWY-CRM(Lyo/Liq) when analyzed by serogroup, overall. No related serious adverse events were reported for both presentations.

Conclusion
After ageing, the new MenACWY-CRM Liquid demonstrated the ability to elicit non-inferior bactericidal responses against MenA compared to licensed formulation. The new full-liquid presentation is expected to increase the user-friendliness of the vaccine as well as to reduce reconstitution errors in the future, with a similar safety profile to that of the licensed vaccine presentation.

Disclosures
Javier Díez-Domingo, MD, PhD, GSK (Grant/Research Support)Sanofi (Grant/Research Support) Corinne Vandermeulen, MD PhD, GSK (Grant/Research Support)MSD (Grant/Research Support)Pfizer (Grant/Research Support) Tauseefullah Akhund, MD, MSc, MPH, GSK (Employee, Shareholder) Marco Costantini, MSc, MBA, EMPHA, GSK (Employee) Puneet Vir Singh, MBBS, PGDCD, GSK (Employee, Shareholder) Venere Basile, MSc, GSK (Employee, Shareholder) Elena Fragapane, MD, GSK (Employee, Shareholder) Maria Lattanzi, MD, PhD, GSK (Employee, Shareholder) Michele Pellegrini, MD, PhD, Michele Pellegrini (Employee, Shareholder)