Moderate to Severe Asthma
Conditions
Keywords
Tezepelumab, Humoral Immune Response, Quadrivalent Influenza Vaccination, Antibody response, Subcutaneous
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.
Interventions
DRUGTezepelumab
210 mg SC injection Q4W.
DRUGPlacebo
SC injection Q4W.
Sponsors
Amgen
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Neither the participant nor any of the investigators or sponsor staff who are involved in the treatment or clinical evaluation and monitoring of the participants will be aware of the treatment received. Since tezepelumab and placebo are not visually distinct, study intervention will be handled by a qualified person (eg, pharmacist or study nurse) at the site.
Eligibility
Sex/Gender
ALL
Age
12 Years to 21 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
This study was conducted in 15 study centres in the United States between 23 August 2021 and 18 July 2022.
Pre-assignment details
The Screening period was 2 to 3 weeks before randomisation. Patients were randomised in a 1:1 ratio to receive tezepelumab or placebo. All the study assessments were performed as per the Schedule of Activities.
Participants by arm
| Arm | Count |
|---|---|
| Tezepelumab Patients received at least 1 injection of tezepelumab 210 mg administered subcutaneously every 4 weeks by APFS | 35 |
| Placebo Patients received at least 1 injection of placebo administered subcutaneously every 4 weeks by APFS | 35 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Tezepelumab | Total |
|---|---|---|---|
| Age, Continuous | 16.6 years STANDARD_DEVIATION 3.1 | 16.3 years STANDARD_DEVIATION 2.3 | 16.5 years STANDARD_DEVIATION 3 |
| Age, Customized 85 years and over | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 21 Participants | 22 Participants | 43 Participants |
| Age, Customized Adults (18-64 years) | 14 Participants | 13 Participants | 27 Participants |
| Age, Customized Children (2-11 years) | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized From 65-84 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized In utero | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Newborns (0-27 days) | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Preterm newborn infants (gestational age < 37 wks) | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 8 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 27 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 12 Participants | 8 Participants | 20 Participants |
| Race/Ethnicity, Customized White | 23 Participants | 24 Participants | 47 Participants |
| Sex: Female, Male Female | 11 Participants | 14 Participants | 25 Participants |
| Sex: Female, Male Male | 24 Participants | 21 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 1 / 35 |
| other Total, other adverse events | 14 / 35 | 15 / 35 |
| serious Total, serious adverse events | 0 / 35 | 1 / 35 |
Outcome results
Primary
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
Population: 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.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Tezepelumab | 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 | Influenza B Yamagata Lineage | 15.2 Percentage of participants | 90% Confidence Interval 6.17 |
| Tezepelumab | 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 | Influenza A H1N1 | 78.8 Percentage of participants | 90% Confidence Interval 63.82 |
| Tezepelumab | 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 | Influenza B Victoria Lineage | 30.3 Percentage of participants | 90% Confidence Interval 17.46 |
| Placebo | 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 | Influenza B Yamagata Lineage | 15.2 Percentage of participants | 90% Confidence Interval 6.17 |
| Placebo | 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 | Influenza A H1N1 | 51.5 Percentage of participants | 90% Confidence Interval 36.07 |
| Placebo | 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 | Influenza B Victoria Lineage | 39.4 Percentage of participants | 90% Confidence Interval 25.11 |
Primary
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
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Tezepelumab | 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 | Influenza A H1N1 | 81.8 Percentage of participants | 90% Confidence Interval 67.24 |
| Tezepelumab | 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 | Influenza A H3N2 | 60.6 Percentage of participants | 90% Confidence Interval 44.82 |
| Tezepelumab | 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 | Influenza B Victoria Lineage | 54.5 Percentage of participants | 90% Confidence Interval 38.94 |
| Tezepelumab | 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 | Influenza B Yamagata Lineage | 51.5 Percentage of participants | 90% Confidence Interval 36.07 |
| Placebo | 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 | Influenza B Victoria Lineage | 63.6 Percentage of participants | 90% Confidence Interval 47.84 |
| Placebo | 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 | Influenza A H1N1 | 75.8 Percentage of participants | 90% Confidence Interval 60.49 |
| Placebo | 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 | Influenza A H3N2 | 51.5 Percentage of participants | 90% Confidence Interval 36.07 |
| Placebo | 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 | Influenza B Yamagata Lineage | 36.4 Percentage of participants | 90% Confidence Interval 22.5 |
Primary
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
Population: 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.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Tezepelumab | Percentage of Patients With Post-vaccination Strain-specific HAI Antibody Titer ≥ 40 | Influenza B Victoria Lineage | 100 Percentage of participants | 90% Confidence Interval 91.32 |
| Tezepelumab | Percentage of Patients With Post-vaccination Strain-specific HAI Antibody Titer ≥ 40 | Influenza A H1N1 | 100 Percentage of participants | 90% Confidence Interval 91.32 |
| Tezepelumab | Percentage of Patients With Post-vaccination Strain-specific HAI Antibody Titer ≥ 40 | Influenza B Yamagata Lineage | 97 Percentage of participants | 90% Confidence Interval 86.41 |
| Placebo | Percentage of Patients With Post-vaccination Strain-specific HAI Antibody Titer ≥ 40 | Influenza B Victoria Lineage | 97.0 Percentage of participants | 90% Confidence Interval 86.41 |
| Placebo | Percentage of Patients With Post-vaccination Strain-specific HAI Antibody Titer ≥ 40 | Influenza A H1N1 | 100 Percentage of participants | 90% Confidence Interval 91.32 |
| Placebo | Percentage of Patients With Post-vaccination Strain-specific HAI Antibody Titer ≥ 40 | Influenza B Yamagata Lineage | 100 Percentage of participants | 90% Confidence Interval 91.32 |
Primary
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
Population: 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.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Tezepelumab | Percentage of Patients With Post-vaccination Strain-specific MN Antibody Titer ≥ 40 | Influenza B Victoria Lineage | 78.8 Percentage of participants | 90% Confidence Interval 63.82 |
| Tezepelumab | Percentage of Patients With Post-vaccination Strain-specific MN Antibody Titer ≥ 40 | Influenza A H1N1 | 100 Percentage of participants | 90% Confidence Interval 91.32 |
| Tezepelumab | Percentage of Patients With Post-vaccination Strain-specific MN Antibody Titer ≥ 40 | Influenza A H3N2 | 93.9 Percentage of participants | 90% Confidence Interval 82.13 |
| Tezepelumab | Percentage of Patients With Post-vaccination Strain-specific MN Antibody Titer ≥ 40 | Influenza B Yamagata Lineage | 97 Percentage of participants | 90% Confidence Interval 86.41 |
| Placebo | Percentage of Patients With Post-vaccination Strain-specific MN Antibody Titer ≥ 40 | Influenza B Yamagata Lineage | 100 Percentage of participants | 90% Confidence Interval 91.32 |
| Placebo | Percentage of Patients With Post-vaccination Strain-specific MN Antibody Titer ≥ 40 | Influenza B Victoria Lineage | 81.8 Percentage of participants | 90% Confidence Interval 67.24 |
| Placebo | Percentage of Patients With Post-vaccination Strain-specific MN Antibody Titer ≥ 40 | Influenza A H3N2 | 97 Percentage of participants | 90% Confidence Interval 86.41 |
| Placebo | Percentage of Patients With Post-vaccination Strain-specific MN Antibody Titer ≥ 40 | Influenza A H1N1 | 93.9 Percentage of participants | 90% Confidence Interval 82.13 |
Primary
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
Population: 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 Microneutralization 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tezepelumab | Post-vaccination Strain-specific Hemagglutination Inhibition (HAI) Antibody Geometric Mean Fold Rises (GMFRs) | Influenza A H1N1 | 7.34 Fold change | Geometric Coefficient of Variation 1.361 |
| Tezepelumab | Post-vaccination Strain-specific Hemagglutination Inhibition (HAI) Antibody Geometric Mean Fold Rises (GMFRs) | Influenza B Yamagata Lineage | 1.76 Fold change | Geometric Coefficient of Variation 0.955 |
| Tezepelumab | Post-vaccination Strain-specific Hemagglutination Inhibition (HAI) Antibody Geometric Mean Fold Rises (GMFRs) | Influenza B Victoria Lineage | 2.94 Fold change | Geometric Coefficient of Variation 1.054 |
| Placebo | Post-vaccination Strain-specific Hemagglutination Inhibition (HAI) Antibody Geometric Mean Fold Rises (GMFRs) | Influenza A H1N1 | 4.75 Fold change | Geometric Coefficient of Variation 1.455 |
| Placebo | Post-vaccination Strain-specific Hemagglutination Inhibition (HAI) Antibody Geometric Mean Fold Rises (GMFRs) | Influenza B Yamagata Lineage | 1.46 Fold change | Geometric Coefficient of Variation 0.937 |
| Placebo | Post-vaccination Strain-specific Hemagglutination Inhibition (HAI) Antibody Geometric Mean Fold Rises (GMFRs) | Influenza B Victoria Lineage | 2.90 Fold change | Geometric Coefficient of Variation 0.841 |
Comparison: Influenza A H1N1 Ratio of placebo over tezepelumab. Results based on ANCOVA model.90% CI: [0.43, 0.98]
Comparison: Influenza B Yamagata Lineage Ratio of placebo over tezepelumab. Results based on ANCOVA model90% CI: [0.6, 1.15]
Comparison: Influenza B Victoria Lineage Ratio of placebo over tezepelumab. Results based on ANCOVA model90% CI: [0.71, 1.37]
Primary
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
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tezepelumab | Post-vaccination Strain-specific Microneutralization (MN) Antibody GMFRs | Influenza A H3N2 | 4.73 Fold change | Geometric Coefficient of Variation 1.509 |
| Tezepelumab | Post-vaccination Strain-specific Microneutralization (MN) Antibody GMFRs | Influenza B Victoria Lineage | 4.08 Fold change | Geometric Coefficient of Variation 2.279 |
| Tezepelumab | Post-vaccination Strain-specific Microneutralization (MN) Antibody GMFRs | Influenza A H1N1 | 14.56 Fold change | Geometric Coefficient of Variation 2.581 |
| Tezepelumab | Post-vaccination Strain-specific Microneutralization (MN) Antibody GMFRs | Influenza B Yamagata Lineage | 4.00 Fold change | Geometric Coefficient of Variation 1.541 |
| Placebo | Post-vaccination Strain-specific Microneutralization (MN) Antibody GMFRs | Influenza B Victoria Lineage | 5.04 Fold change | Geometric Coefficient of Variation 1.723 |
| Placebo | Post-vaccination Strain-specific Microneutralization (MN) Antibody GMFRs | Influenza A H3N2 | 5.90 Fold change | Geometric Coefficient of Variation 3.18 |
| Placebo | Post-vaccination Strain-specific Microneutralization (MN) Antibody GMFRs | Influenza B Yamagata Lineage | 3.56 Fold change | Geometric Coefficient of Variation 2.206 |
| Placebo | Post-vaccination Strain-specific Microneutralization (MN) Antibody GMFRs | Influenza A H1N1 | 10.62 Fold change | Geometric Coefficient of Variation 2.409 |
Comparison: Influenza A H1N1 Ratio of placebo over tezepelumab. Results based on ANCOVA model90% CI: [0.42, 1.28]
Comparison: Influenza A H3N2 Ratio of placebo over tezepelumab. Results based on ANCOVA model90% CI: [0.72, 2.17]
Comparison: Influenza B Victoria Lineage Ratio of placebo over tezepelumab. Results based on ANCOVA model90% CI: [0.73, 2.07]
Comparison: Influenza B Yamagata Lineage Ratio of placebo over tezepelumab. Results based on ANCOVA model90% CI: [0.54, 1.48]
Primary
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
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tezepelumab | Post-vaccination Strain-specific Serum HAI Antibody Geometric Mean Titers (GMTs) | Influenza B Victoria Lineage | 194.68 Titer | Geometric Coefficient of Variation 1.089 |
| Tezepelumab | Post-vaccination Strain-specific Serum HAI Antibody Geometric Mean Titers (GMTs) | Influenza A H1N1 | 809.23 Titer | Geometric Coefficient of Variation 0.921 |
| Tezepelumab | Post-vaccination Strain-specific Serum HAI Antibody Geometric Mean Titers (GMTs) | Influenza B Yamagata Lineage | 167.46 Titer | Geometric Coefficient of Variation 0.925 |
| Placebo | Post-vaccination Strain-specific Serum HAI Antibody Geometric Mean Titers (GMTs) | Influenza B Victoria Lineage | 200.55 Titer | Geometric Coefficient of Variation 0.948 |
| Placebo | Post-vaccination Strain-specific Serum HAI Antibody Geometric Mean Titers (GMTs) | Influenza A H1N1 | 596.76 Titer | Geometric Coefficient of Variation 1.076 |
| Placebo | Post-vaccination Strain-specific Serum HAI Antibody Geometric Mean Titers (GMTs) | Influenza B Yamagata Lineage | 161.56 Titer | Geometric Coefficient of Variation 0.688 |
Comparison: Influenza A H1N1 Ratio of placebo over tezepelumab. Results based on ANCOVA model90% CI: [0.52, 1.04]
Comparison: Influenza B Yamagata Lineage Ratio of placebo over tezepelumab. Results based on ANCOVA model90% CI: [0.72, 1.29]
Comparison: Influenza B Victoria Lineage Ratio of placebo over tezepelumab. Results based on ANCOVA model90% CI: [0.73, 1.46]
Primary
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
Population: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tezepelumab | Post-vaccination Strain-specific Serum MN Antibody GMTs | Influenza A H3N2 | 600.92 Titer | Geometric Coefficient of Variation 2.154 |
| Tezepelumab | Post-vaccination Strain-specific Serum MN Antibody GMTs | Influenza B Yamagata Lineage | 355.44 Titer | Geometric Coefficient of Variation 1.076 |
| Tezepelumab | Post-vaccination Strain-specific Serum MN Antibody GMTs | Influenza B Victoria Lineage | 125.67 Titer | Geometric Coefficient of Variation 4.687 |
| Tezepelumab | Post-vaccination Strain-specific Serum MN Antibody GMTs | Influenza A H1N1 | 382.55 Titer | Geometric Coefficient of Variation 1.469 |
| Placebo | Post-vaccination Strain-specific Serum MN Antibody GMTs | Influenza A H1N1 | 303.63 Titer | Geometric Coefficient of Variation 1.667 |
| Placebo | Post-vaccination Strain-specific Serum MN Antibody GMTs | Influenza A H3N2 | 457.33 Titer | Geometric Coefficient of Variation 2.336 |
| Placebo | Post-vaccination Strain-specific Serum MN Antibody GMTs | Influenza B Victoria Lineage | 124.35 Titer | Geometric Coefficient of Variation 3.515 |
| Placebo | Post-vaccination Strain-specific Serum MN Antibody GMTs | Influenza B Yamagata Lineage | 366.81 Titer | Geometric Coefficient of Variation 1.27 |
Comparison: Influenza A H1N1 Ratio of placebo over tezepelumab. Results based on ANCOVA model90% CI: [0.51, 1.25]
Comparison: Influenza A H3N2 Ratio of placebo over tezepelumab. Results based on ANCOVA model90% CI: [0.42, 1.28]
Comparison: Influenza B Victoria Lineage Ratio of placebo over tezepelumab. Results based on ANCOVA model90% CI: [0.49, 1.99]
Comparison: Influenza B Yamagata Lineage Ratio of placebo over tezepelumab. Results based on ANCOVA model90% CI: [0.7, 1.52]
Secondary
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
Population: Safety analysis set consisted of all patients who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Tezepelumab | Immunogenicity | Only baseline ADA positive | 0 Patients |
| Tezepelumab | Immunogenicity | Any post-baseline ADA positive | 0 Patients |
| Tezepelumab | Immunogenicity | Treatment-induced ADA positive | 0 Patients |
| Tezepelumab | Immunogenicity | Both baseline and post-baseline ADA positive | 0 Patients |
| Tezepelumab | Immunogenicity | ADA persistently positive | 0 Patients |
| Tezepelumab | Immunogenicity | ADA transiently positive | 0 Patients |
| Tezepelumab | Immunogenicity | Treatment-boosted ADA positive | 0 Patients |
| Tezepelumab | Immunogenicity | Any baseline ADA positive | 0 Patients |
| Tezepelumab | Immunogenicity | TE-ADA positive (ADA incidence) | 0 Patients |
| Tezepelumab | Immunogenicity | ADA prevalence | 0 Patients |
| Placebo | Immunogenicity | TE-ADA positive (ADA incidence) | 4 Patients |
| Placebo | Immunogenicity | ADA transiently positive | 0 Patients |
| Placebo | Immunogenicity | ADA prevalence | 4 Patients |
| Placebo | Immunogenicity | Only baseline ADA positive | 0 Patients |
| Placebo | Immunogenicity | Both baseline and post-baseline ADA positive | 0 Patients |
| Placebo | Immunogenicity | Any baseline ADA positive | 0 Patients |
| Placebo | Immunogenicity | Any post-baseline ADA positive | 4 Patients |
| Placebo | Immunogenicity | Treatment-induced ADA positive | 4 Patients |
| Placebo | Immunogenicity | ADA persistently positive | 4 Patients |
| Placebo | Immunogenicity | Treatment-boosted ADA positive | 0 Patients |
Secondary
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
Population: Pharmacokinetic (PK) analysis set consisted of all patients who received tezepelumab and from whom PK blood samples were obtained and assumed not to be affected by factors such as protocol deviations.~Here, Number of patients analyzed in each row reflects number of patients analyzed for that timepoint
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Tezepelumab | Serum Tezepelumab Concentrations | Week 0 | NA microgram/milliliter (μg/mL) | — |
| Tezepelumab | Serum Tezepelumab Concentrations | Week 12 | 27.00 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 0.5421 |
| Tezepelumab | Serum Tezepelumab Concentrations | Week 16 | 20.76 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 3.6969 |
| Tezepelumab | Serum Tezepelumab Concentrations | Week 28 | 2.79 microgram/milliliter (μg/mL) | Geometric Coefficient of Variation 1.0705 |