04. Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered in Meningococcal Vaccine-Naive Participants Across a Broad Age Range (2-55 Years) in Japan

Background MenACYW-TT [MenQuadfi®] is a quadrivalent meningococcal conjugate vaccine, licensed for use in ages 2 years and older in USA. The vaccine is also licensed in ages 12 months and older in EU and certain other countries. We evaluated the safety and immunogenicity of MenACYW-TT compared to a licensed quadrivalent conjugate meningococcal vaccine (MenACWY-DT [Menactra®]) in Japanese children, adolescents and adults (2-55 years of age). Methods A phase III modified double-blind, randomized study (NCT04368429) to evaluate the immunogenicity and safety of a single dose of MenACYW-TT versus MenACWY-DT was conducted in 360 participants (ratio 1:1) between ages 2 and 55 years in Japan. Serum bactericidal assays with human complement (hSBA) were used to measure antibodies against vaccine serogroups at baseline (Day 0) and 30 days post-vaccination (D30). Safety data were collected up to 30 days post-vaccination. Results Non-inferiority of immune responses for all four serogroups, based on percentages of participants achieving hSBA vaccine seroresponse as primary endpoint, was demonstrated for MenACYW-TT compared to MenACWY-DT at Day 30 in comparison to baseline: 85.6% vs 65.4% for serogroup A, 96.6% vs 62.6% for serogroup C, 87.4% vs 49.2% for serogroup W, and 97.7% vs 63.5% for serogroup Y. The proportions of individuals with hSBA titers ≥ 1:8 following MenACYW-TT administration were higher than those after MenACWY-DT administration for serogroups C (98.9% vs 81.0%), W (99.4% vs 91.1%) and Y (100 % vs 89.4%) and comparable for serogroup A (96.6% vs 92.7%). The hSBA GMTs were higher following administration of MenACYW-TT for all four serogroups. Immunogenicity results in participants 10 to 17 years of age and ≥ 18 years of age were comparable to those in the whole population (2-55 years). The safety profiles of MenACYW-TT and MenACWY-DT were comparable. There were no immediate adverse events (AEs), no AEs leading to study discontinuation, and no vaccine-related serious adverse events reported in the study. Conclusion MenACYW-TT vaccine was well tolerated and demonstrated a non-inferior immune response compared to that for the licensed MenACWY-DT vaccine when administered as a single dose to meningococcal vaccine-naïve children, adolescents, and adults in Japan. Disclosures Osamu Matsuoka, MD, Sanofi Pasteur (Scientific Research Study Investigator, Research Grant or Support) Mugen Ujiie, MD, Sanofi Pasteur (Scientific Research Study Investigator, Research Grant or Support) Hitoshi Kikuchi, MD, Sanofi Pasteur (Scientific Research Study Investigator)Sanofi Pasteur (Research Grant or Support) Danaya Chansinghakul, MD, Sanofi Pasteur (Employee) Takahiro Inoue, MSc, Sanofi Pasteur (Employee) Kucku Varghese, PhD, Sanofi Pasteur (Employee) Nuchra Sirisuphmitr, MSc, Sanofi Pasteur (Employee) Tomoyuki Hashiguchi, MSc, Sanofi Pasteur (Employee) Betzana Zambrano, MD, Sanofi Pasteur (Employee) Takahiro Nakama, MD, Sanofi Pasteur (Employee) Carina Frago, MD, Sanofi Pasteur (Employee, Shareholder) Emilia Jordanov, MD, Sanofi Pasteur (Employee, Shareholder) Mandeep S. Dhingra, MD, Sanofi Pasteur (Employee, Shareholder)

03. Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered as a Booster Dose in Adults and Adolescents Vaccinated Against Meningococcal Disease 3 - 6 Years Earlier

Background Booster doses of meningococcal conjugate vaccines may induce long-term protection against invasive meningococcal disease. MenACYW-TT [MenQuadfi®] is a quadrivalent meningococcal conjugate vaccine, licensed for use in ages 2 years and older in USA. The vaccine is also licensed in ages 12 months and older in EU and other countries. Methods A phase IIIb study (NCT04084769) was conducted to evaluate the persistence of immune response in adults and adolescents primed 3-6 years earlier with either MenACYW-TT or MCV4-CRM (Menveo®) and, safety and immunogenicity of MenACYW-TT when administered as a booster dose with or without concomitant administration with MenB vaccines (Bexsero® and Trumenba®). Serum bactericidal assays with human complement (hSBA) and baby rabbit complement (rSBA) were used to measure antibodies against vaccine serogroups at baseline (Day 0 [D0]), D06 (in a subset) and 30 days post-vaccination (D30). Safety data were collected up to 6 months post-vaccination. Results At D0, the GMTs were higher in subjects primed with MenACYW-TT vs MCV4-CRM for serogroups C, Y and W, and were comparable for serogroup A. At D0, all hSBA GMTs were higher than those observed pre-priming dose, suggesting persistence of immunity. Sufficiency of hSBA seroresponse ( >75%) was demonstrated following administration of MenACYW-TT booster dose regardless of the priming vaccine administered 3-6 years earlier. Vaccine seroresponse in a subset of participants at D06 ranged from 77.8% (95%CI 62.9%; 88.8%) for serogroup A to 97.8% (88.5%; 99.9%) for serogroup W suggesting a quick onset of immune response post-booster. Post-vaccination (D30) hSBA GMTs were comparable for serogroups A, Y and W regardless of the nature of the priming vaccine and were higher for serogroup C in subjects primed with MenACYW-TT vaccine. The MenACYW-TT booster dose was well-tolerated and had similar safety profiles regardless of the priming vaccine. The safety profiles were comparable regardless of the MenB vaccine co-administered with MenACYW-TT vaccine. Conclusion MenACYW-TT used as priming vaccine was able to demonstrate persistence of immune response 3-6 years later. MenACYW-TT elicits robust booster responses in adults and adolescents primed with MenACYW-TT or MCV4-CRM Disclosures Betzana Zambrano, MD, Sanofi Pasteur (Employee) Germán Áñez, MD, Sanofi Pasteur (Other Financial or Material Support, Former employee) Sue Jiayuan, MSc, Sanofi Pasteur (Independent Contractor) Judy Pan, PhD, Sanofi Pasteur (Employee) Habiba Arroum, MD, Sanofi Pasteur (Employee) Kucku Varghese, PhD, Sanofi Pasteur (Employee) Emilia Jordanov, MD, Sanofi Pasteur (Employee, Shareholder) Mandeep S. Dhingra, MD, Sanofi Pasteur (Employee, Shareholder)

1046. Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered as a Booster to Adults ≥ 59 Years of Age

Background MenACYW-TT (MenQuadfi®, Sanofi) is a quadrivalent (serogroups A, C, W, and Y) meningococcal tetanus toxoid conjugate vaccine. It was recently approved for use in persons aged ≥ 2 years in the US and persons aged ≥ 1 year in Europe and certain other countries; trials in infants as young as 6 weeks are ongoing. This study evaluated seroresponse after a MenACYW-TT booster given to adults who received either quadrivalent meningococcal polysaccharide vaccine (MSPV4) or MenACYW-TT three years earlier at age ≥ 56 years. Immune persistence up to 7 years after primary vaccination was also evaluated. Methods This was a Phase 3 randomized, open-label study (NCT04142242) of adults aged ≥ 59 years who participated in previous studies of MenACYW-TT vs MPSV4 (NCT01732627 and NCT02842866). The study was conducted in the US and Puerto Rico. Immune response and persistence were assessed with a serum bactericidal assay using human complement (hSBA). Sufficiency of the vaccine seroresponse was considered demonstrated if the lower limit of the 1-sided 97.5% CI for the percentage of subjects with an hSBA vaccine seroresponse against serogroups A, C, W and Y was > 40%. Safety data were collected up to 30 days after booster vaccination. Results A total of 471 persons were enrolled. Sufficiency of a MenACYW-TT booster was demonstrated for MPSV4- and for MenACYW-TT-primed subjects. hSBA seroresponse rates were higher among MenACYW-TT- vs MPSV4-primed subjects (79.3%–93.1% vs 49.2%–60.8%, respectively). Three to 7 years after primary vaccination, hSBA geometric mean titers (GMTs) and seroprotection rates (SPRs) declined in both MenACYW-TT- and MPSV4-primed subjects, with hSBA GMTs and SPRs for serogroups C, W, and Y generally remaining higher for MenACYW-TT- vs MPSV4-primed subjects; those for serogroup A were similar regardless of priming vaccine. Rates of adverse events following a MenACYW-TT booster were similar between MenACYW-TT- and MPSV4-primed subjects. No safety concerns were identified. Conclusion A MenACYW-TT booster was well tolerated and immunogenic when administered to either MPSV4- or MenACYW-primed adults aged ≥ 59 years. Up to 7 years after primary vaccination, immune persistence for serogroups C, W, and Y tended to be greater for MenACYW-TT vs MPSV4. Disclosures Corwin A. Robertson, MD, MPH, FACP, Sanofi Pasteur (Employee, Other Financial or Material Support, Stockholder) Alexandre Selmani, PhD, Sanofi Pasteur (Employee) Katherine Galarza, MD, Sanofi Pasteur (Employee) Philipp Oster, MD, Sanofi Pasteur (Employee, Stockholder)

1243. Semi-Quantitative Benefit-Risk Assessment for a New Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) in Individuals 2 Years of Age and Older

Background MenACYW-TT is a new quadrivalent meningococcal conjugate vaccine approved by the US FDA for use in individuals 2 years and older. We present the structured benefit-risk assessment conducted by Sanofi Pasteur in support of the initial biological license application for MenACYW-TT. Methods The safety and immunogenicity of MenACYW-TT in subjects ≥ 2 years was evaluated in 5 pivotal randomized, active-controlled clinical trials. Collectively, 4,919 subjects received either a single primary dose (n=4517) or a booster dose (n=402) of MenACYW-TT. A semi-quantitative framework was used to establish favorable and unfavorable effects of MenACYW-TT relative to comparators: MenACWY-CRM in children 2-9 years and adolescents 10-17 years, MenACWY-D in adolescents 10-17 years and adults 18-55 years, and MPSV4 in older adults ≥ 56 years. Benefit outcome measures included vaccine seroresponse and seroprotection (titers ≥ 1:8) at D30 evaluated by serum bactericidal assay using human complement, for each serogroup. Risk outcome measures included rates of solicited injection site and systemic reactions (including grade 3 reactions) within 7 days after vaccination, and rates of serious adverse events within 6 months after vaccination. The differences in rates for MenACWY-TT vs comparator vaccines were calculated along with 95% confidence intervals. Results For all benefit criteria, and in all age groups, rate differences favored MenACYW-TT in meningococcal vaccine-naïve individuals. Immune response differences were more pronounced for serogroup C. Differences showed favorable (seroresponse criteria) or comparable (seroprotection criteria) effects for MenACYW-TT in adolescents and adults previously primed with MenACWY-D or MenACWY-CRM. For the risk criteria, rate differences generally showed comparable effects between MenACYW-TT and MenACWY-D or MenACWY-CRM in children, adolescents and adults, while the rate differences for both solicited injection site and systemic reactions favored MPSV4 in older adults. The latter was possibly due to the use of a protein carrier in MenACYW-TT. Conclusion The benefit risk-profile of MenACYW-TT in individuals ≥ 2 years is considered favorable relative to comparator licensed vaccines. Disclosures David Neveu, MPharm, Sanofi Pasteur (Employee) Marie-Laure Kürzinger, MSc, Sanofi (Employee) Aiying Chen, PhD, Sanofi Pasteur (Employee) Mandeep S. Dhingra, MD, Sanofi Pasteur (Employee)