This is a Phase 3b, multicenter, randomized, double-blind, parallel group, placebo-controlled study designed to investigate the potential effect of tezepelumab (210 mg subcutaneous \[SC\] every 4 weeks \[Q4W\]) on antibody responses following seasonal quadrivalent influenza virus vaccination in the fall/winter 2021-2022 in the USA.
Participants with moderate to severe asthma will enter the screening period of a minimum of 2 weeks to allow adequate time for all of the eligibility criteria to be evaluated. They will be randomized 1:1 to receive tezepelumab 210 mg or placebo SC Q4W, administered at Weeks 0, 4, 8 and 12. Randomization will be monitored to ensure at least 50% of the randomized participants are between the ages of 12 to 17 years. Participants will receive a single dose of inactivated quadrivalent seasonal influenza vaccine intramuscularly at Week 12, prior to the fourth dose of study intervention. Serum samples for evaluation of antibody response will be drawn at Week 12 (pre-vaccination) and at Week 16 (4 weeks post-vaccination) when humoral response to the vaccination is expected to be fully developed. The End of Treatment (EOT) Visit will be conducted at Week 16 and a final Follow-up Visit and the End of Study Visit will be conducted at Week 28.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
70
210 mg SC injection Q4W.
SC injection Q4W.
Research Site
Bakersfield, California, United States
Research Site
Huntington Beach, California, United States
Research Site
Miami, Florida, United States
Post-vaccination Strain-specific Hemagglutination Inhibition (HAI) Antibody Geometric Mean Fold Rises (GMFRs)
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed. HAI assay was not performed for H3N2 strain due to the known low haemagglutination effect.
Time frame: From Week 12 to Week 16
Post-vaccination Strain-specific Microneutralization (MN) Antibody GMFRs
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed.
Time frame: From Week 12 to Week 16
Post-vaccination Strain-specific Serum HAI Antibody Geometric Mean Titers (GMTs)
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed. HAI assay was not performed for H3N2 strain due to the known low haemagglutination effect.
Time frame: Week 16
Post-vaccination Strain-specific Serum MN Antibody GMTs
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed.
Time frame: Week 16
Percentage of Patients With Post-vaccination Strain-specific Antibody Response at Week 16 With Antibody Response Defined as a ≥ 4-fold Rise in HAI Antibody Titer
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed. HAI assay was not performed for H3N2 strain due to the known low haemagglutination effect.
Time frame: Week 16
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Research Site
Columbia, Missouri, United States
Research Site
Northfield, New Jersey, United States
Research Site
Dayton, Ohio, United States
Research Site
Toledo, Ohio, United States
Research Site
Edmond, Oklahoma, United States
Research Site
Oklahoma City, Oklahoma, United States
Research Site
Dallas, Texas, United States
...and 5 more locations
Percentage of Patients With Post-vaccination Strain-specific Antibody Response at Week 16 With Antibody Response Defined as a ≥ 4-fold Rise in MN Antibody Titer
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed. Vaccine immunogenicity analysis set consisted of all randomised patients who received the influenza vaccine plus at least 1 dose of tezepelumab or placebo, had pre and post vaccination HAI or MN antibody measurements, had no influenza infection prior to Visit 7 (Week 16), and had no protocol deviation, judged to have the potential to interfere with the generation or interpretation of an antibody response.
Time frame: Week 16
Percentage of Patients With Post-vaccination Strain-specific HAI Antibody Titer ≥ 40
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed. HAI assay was not performed for H3N2 strain due to the known low haemagglutination effect.
Time frame: Week 16
Percentage of Patients With Post-vaccination Strain-specific MN Antibody Titer ≥ 40
Effect of tezepelumab on the humoral immune response following seasonal influenza virus vaccination in adolescent and young adult participants with moderate to severe asthma was assessed.
Time frame: Week 16
Serum Tezepelumab Concentrations
Tezepelumab serum concentrations were summarized using descriptive statistics at each visit.
Time frame: Week 0, Week 12, Week 16 and Week 28
Immunogenicity
Immunogenicity assessments were performed. ADA prevalence was defined as patients who are ADA positive at any time including baseline. Persistently positive was defined as having at least two post-baseline ADA positive measurements (with ≥16 weeks between first and last positive) or an ADA positive result at the last available post-baseline assessment. Transiently positive was defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Treatment boosted ADA was defined as baseline positive ADA titre that was boosted to a 4-fold or higher-level following treatment. Treatment emergent ADA (ADA incidence) was defined as the sum of treatment induced ADA and treatment boosted ADA.
Time frame: From Baseline to Week 28