160 - Safety and Immunogenicity of Escalating Dose Formulations of High-dose Quadrivalent Influenza Vaccine in Children 6 Months Through < 18 Years of Age

Background: Children do not respond immunologically as well as adults to standard-dose (SD) influenza vaccination and remain at increased risk of influenza and its complications. A method to improve efficacy in children may be to increase antigen amount per dose, a successful strategy used in older adults. Trivalent high-dose (HD) influenza vaccine (60ug hemagglutinin/strain) showed significantly improved effectiveness for prevention of clinical outcomes related to influenza in adults ≥65 years; moreover, a quadrivalent HD formulation was approved by US FDA (2019) for use in this group.

Methods: A Phase 2, randomized, modified double blind study (NCT03698279) was conducted in US and Canadian children to evaluate safety and immunogenicity of IIV4-HD compared to an IIV4-SD and adjuvanted trivalent influenza vaccine (aIIV3). Children (n=661, 6 months through < 18 years) were assigned to receive intramuscularly 1 of 3 formulations of IIV4-HD (30, 45, or 60 µg HA/strain/dose), a licensed IIV4-SD, or a licensed aIIV3. Depending on child’s previous influenza vaccination status and age, they received 1 or 2 doses of study vaccine 28 days apart. Post-vaccination (28 days after each vaccination) geometric mean titers (GMTs) and seroconversion rates were measured using hemagglutinin inhibition (HAI) assay. Reactogenicity data were collected through 1 week; safety data were collected through 6 months post-vaccination.

Results: IIV4-HD was more reactogenic than IIV4-SD, but unsolicited related adverse events were similar (Table 1). No related serious adverse events or deaths occurred. A dose-related increase in HAI GMT ratio was observed across the age range for A/H3N2 but only in children 6 months through < 3 years for A/H1N1 and the 2 B strains (Table 2). Compared with IIV4-SD, the 60 µg HA/strain/dose formulation of IIV4-HD generated highest HAI GMT ratios and high seroconversion rates for all 4 strains in US children 6 months through < 3 years. Canadian children receiving IIV4-HD generated HAI titers incongruent to those of US children receiving IIV4-HD, limiting direct comparison against aIIV3.Safety Overview (US and Canadian subjects 6 months through <18 years)
HAI GMT Ratios (QIV-HD/QIV-SD) at 28 days After the Last Vaccination (US subjects 6 months through <18 years)


Conclusion: The favorable safety profile and the HAI GMT ratios support pediatric dose selection of 60µg HA/strain/dose as most appropriate to evaluate in Phase 3.

Presenting Author(s)

• 

  Leejah Chang, MD

  Senior Director
  Sanofi Pasteur
  Easton, PA

  Disclosure: Sanofi Pasteur (Employee)

  Slides Slides and Audio

Co-Author(s)

• EA

  Evan J. Anderson, MD

  Infectious Diseases Physician
  Emory University, Atlanta VA Medical Center
  Atlanta, Georgia

  Disclosure: Sanofi Pasteur (Scientific Research Study Investigator)
• RJ

  Robert Jeanfreau, MD

  Investigator
  MedPharmics
  Metarie, Louisiana

  Disclosure: Sanofi Pasteur (Scientific Research Study Investigator)
• YH

  Ying He, PhD

  Biostatistician
  Sanofi Pasteur
  Virginia Beach, Virginia

  Disclosure: Otsuka Pharmaceutical (Employee)Sanofi Pasteur (Other Financial or Material Support, Former employee)
• BH

  Bryony Hicks, BSc

  Regional Trial Manager
  Sanofi Pasteur
  Toronto, Ontario, Canada

  Disclosure: Sanofi Pasteur (Employee)
• AS

  Anju Shrestha, MD

  Director
  Sanofi Pasteur
  Swiftwater, Pennsylvania

  Disclosure: Sanofi Pasteur (Employee)
• AP

  Aseem Pandey, PhD

  Deputy Director
  Sanofi Pasteur
  Swiftwater, Pennsylvania

  Disclosure: Sanofi Pasteur (Employee)Sanofi Pasteur (Employee)
• RK

  Rawia Khoury, BSc

  Medical Writer
  Sanofi Pasteur
  Swiftwater, Pennsylvania

  Disclosure: Sanofi Pasteur (Employee)
• ID

  Iris De Bruijn, PhD

  Associate Vice President
  Sanofi Pasteur
  Marcy L'Etoile, Rhone-Alpes, France

  Disclosure: Sanofi Pasteur (Employee)
• VL

  Victoria Landolfi, MS, MBA

  Associate Vice President
  Sanofi Pasteur
  Swiftwater, Pennsylvania

  Disclosure: Sanofi Pasteur (Employee)