title: Safety of a quadrivalent meningococcal serogroups A, C, W and Y conjugate vaccine (MenACWY-CRM) administered with routine infant vaccinations: results of an open-label, randomized, phase 3b controlled study in healthy infants.
abstract: BACKGROUND
  The highest risk for invasive meningococcal disease (IMD) is in infants aged <1 year. Quadrivalent meningococcal conjugate vaccination has the potential to prevent IMD caused by serogroups A, C, W and Y. This phase 3b, multinational, open-label, randomized, parallel-group, multicenter study evaluated the safety of a 4-dose series of MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, concomitantly administered with routine vaccinations to healthy infants.
  
  
  METHODS
  Two-month-old infants were randomized 3:1 to receive MenACWY-CRM with routine vaccines or routine vaccines alone at ages 2, 4, 6 and 12 months. Adverse events (AEs) that were medically attended and serious adverse events (SAEs) were collected from all subjects from enrollment through 18 months of age. In a subset, detailed safety data (local and systemic solicited reactions and all AEs) were collected for 7 days post vaccination. The primary objective was a non-inferiority comparison of the percentages of subjects with ≥1 severe systemic reaction during Days 1-7 after any vaccination of MenACWY-CRM plus routine vaccinations versus routine vaccinations alone (criterion: upper limit of 95% confidence interval [CI] of group difference <6%).
  
  
  RESULTS
  A total of 7744 subjects were randomized with 1898 in the detailed safety arm. The percentage of subjects with severe systemic reactions was 16% after MenACWY-CRM plus routine vaccines and 13% after routine vaccines alone (group difference 3.0% (95% CI -0.8, 6.4%). Although the non-inferiority criterion was not met, post hoc analysis controlling for significant center and group-by-center differences revealed that MenACWY-CRM plus routine vaccinations was non-inferior to routine vaccinations alone (group difference -0.1% [95% CI -4.9%, 4.7%]). Rates of solicited AEs, medically attended AEs, and SAEs were similar across groups.
  
  
  CONCLUSIONS
  In a large multinational safety study, a 4-dose series of MenACWY-CRM concomitantly administered with routine vaccines was clinically acceptable with a similar safety profile to routine vaccines given alone.
authors.affiliation: Instituto de Atención Pediatrica, Apdo 607-1150 La Uruca, San Jose, Costa Rica.
authors.forename: Arturo
authors.initials: A
authors.lastname: Abdelnour
authors.affiliation: Wee Care Pediatrics, 2084N 1700W Suite A, Layton, UT, United States.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Silas
authors.affiliation: Guanchipelin, San Rafael, Escazu, Heredia, Costa Rica.
authors.forename: Marta Raquel Valdés
authors.initials: MR
authors.lastname: Lamas
authors.affiliation: Centro de Investigaciones en Pediatría, Guatemala City, Guatemala.
authors.forename: Carlos Fernándo Grazioso
authors.initials: CF
authors.lastname: Aragón
authors.affiliation: Department of Pediatrics, Mackay Memorial Hospital, 92, Sec. 2, Zhongshan N. Rd., Zhongshan District, Taipei City 104, Taiwan.
authors.forename: Nan-Chang
authors.initials: NC
authors.lastname: Chiu
authors.affiliation: Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung University College of Medicine, No.199, Tunghwa Rd., Taipei, Taiwan.
authors.forename: Cheng-Hsun
authors.initials: CH
authors.lastname: Chiu
authors.affiliation: Instituto de Investigación Nutricional, Av. La Molina 1885, Lima 12, Peru.
authors.forename: Teobaldo Herrera
authors.initials: TH
authors.lastname: Acuña
authors.affiliation: Hospital Materno Infantil José Domingo de Obaldía, Ciudad de David, Chiriqui, Panama.
authors.forename: Tirza De León
authors.initials: Tde L
authors.lastname: Castrejón
authors.affiliation: Novartis Vaccines and Diagnostics, Inc., 350 Massachusetts Avenue, Cambridge, MA 02139, United States.
authors.forename: Allen
authors.initials: A
authors.lastname: Izu
authors.affiliation: Novartis Vaccines and Diagnostics, Inc., 350 Massachusetts Avenue, Cambridge, MA 02139, United States.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Odrljin
authors.affiliation: Novartis Vaccines and Diagnostics, Inc., 350 Massachusetts Avenue, Cambridge, MA 02139, United States.
authors.forename: Igor
authors.initials: I
authors.lastname: Smolenov
authors.affiliation: Novartis Vaccines and Diagnostics, Inc., 350 Massachusetts Avenue, Cambridge, MA 02139, United States.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hohenboken
authors.affiliation: Novartis Vaccines and Diagnostics, Inc., 350 Massachusetts Avenue, Cambridge, MA 02139, United States. Electronic address: peter.dull@novartis.com.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Dull
mesh_terms: D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D008297:Male; D008589:Meningococcal Infections / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: C525703:MenACWY; D022401:Meningococcal Vaccines; D018074:Vaccines, Conjugate
keywords: AE; Adverse events; DTaP; H. influenzae type b [vaccine]; Hib; IM; IMD; IPV; Infant; MenACWY-CRM; Meningococcal; SAE; Safety; Vaccine; adverse event; diphtheria, tetanus, pertussis [vaccine]; inactivated polio vaccine; intramuscular; invasive meningococcal disease; serious adverse event