Study to Assess the Effect of Tezepelumab on the Immune Response to Influenza Vaccination in Participants With Asthma

Phase 3

Completed

Conditions: Moderate to Severe Asthma

Interventions: Drug: Tezepelumab
Drug: Placebo

Registration Number: NCT05062759

Lead Sponsor: AstraZeneca

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 70

Inclusion Criteria

Documented physician-diagnosed asthma for at least 12 months prior to Visit 1.
Morning pre-bronchodilator FEV1 (Forced expiratory volume) of > 50% predicted normal value at Visit 1 or Visit 2.
Body weight ≥ 40 kg.
For women of childbearing potential, a negative urine pregnancy test is required prior to administration of study intervention at Visit 3.
Must have 'not well-controlled' asthma.

Exclusion Criteria

Clinically important pulmonary disease other than asthma.
Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment.
Life-threatening asthma
History of cancer.
Allergy to eggs, if egg based influenza vaccine will be administered.
History of anaphylaxis to any biologic therapy.
Current smokers or participants with smoking history ≥ 10 pack-years and participants using vaping products, including electronic cigarettes. Former smokers with a smoking history of < 10 pack-years and users of vaping or e-cigarette products must have stopped for at least 6 months prior to Visit 1 to be eligible.
History of alcohol or drug abuse within 12 months prior to the date of informed consent.
Major surgery within 8 weeks prior to Visit 1 or planned surgical procedures during the conduct of the study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tezepelumab	Tezepelumab	Participants will be randomized to receive tezepelumab 210 mg administered at Weeks 0, 4, 8 and 12. Participants will also receive a single dose of inactivated quadrivalent seasonal influenza vaccine intramuscularly at Week 12, prior to the fourth dose of study intervention.
Placebo to Tezepelumab	Placebo	Participants will be randomized to receive placebo SC Q4W, administered at Weeks 0, 4, 8 and 12. Participants will also receive a single dose of inactivated quadrivalent seasonal influenza vaccine intramuscularly at Week 12, prior to the fourth dose of study intervention.

Primary Outcome Measures

Name	Time	Method
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	Week 16	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.
Post-vaccination Strain-specific Hemagglutination Inhibition (HAI) Antibody Geometric Mean Fold Rises (GMFRs)	From Week 12 to Week 16	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.
Post-vaccination Strain-specific Microneutralization (MN) Antibody GMFRs	From Week 12 to Week 16	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.
Post-vaccination Strain-specific Serum HAI Antibody Geometric Mean Titers (GMTs)	Week 16	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.
Percentage of Patients With Post-vaccination Strain-specific HAI Antibody Titer ≥ 40	Week 16	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.
Post-vaccination Strain-specific Serum MN Antibody GMTs	Week 16	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.
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	Week 16	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.
Percentage of Patients With Post-vaccination Strain-specific MN Antibody Titer ≥ 40	Week 16	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.

Secondary Outcome Measures

Name	Time	Method
Immunogenicity	From Baseline to Week 28	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.
Serum Tezepelumab Concentrations	Week 0, Week 12, Week 16 and Week 28	Tezepelumab serum concentrations were summarized using descriptive statistics at each visit.