Phase 3
N=1,061
Study to Evaluate Tezepelumab in Adults & Adolescents With Severe Uncontrolled Asthma
Asthma
Bottom Line
View on ClinicalTrials.gov: NCT03347279 ↗Enrolled (actual)
1,061
Serious AEs
11.8%
Results posted
Nov 2021
Primary outcome: Primary: Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma — 0.93; 2.10 events per year — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Experimental: Tezepelumab (Biological); Placebo (Other)
- Age
- Pediatric, Adult, Older Adult · 12+ yrs
- Sex
- All
- Sponsor
- AstraZeneca
- Primary completion
- Sep 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma |
0.93; 2.10 | <0.001 sig |
| PRIMARY Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma in Subjects With Baseline Eosinophils < 300 Cells/uL |
1.02; 1.73 | <0.001 sig |
| SECONDARY Mean Change From Baseline at Week 52 in Pre-dose/Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in 1 Second (FEV1) (L) (Key Secondary Endpoint) |
0.23; 0.10 | <0.001 sig |
| SECONDARY Mean Change From Baseline at Week 52 in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) Total Score (Key Secondary Endpoint) |
1.48; 1.14 | <0.001 sig |
| SECONDARY Mean Change From Baseline at Week 52 in Asthma Control Questionnaire-6(ACQ-6) (Key Secondary Endpoint) |
-1.53; -1.20 | <0.001 sig |
| SECONDARY Mean Change From Baseline at Week 52 in Asthma Symptom Diary (Key Secondary Endpoint) |
-0.70; -0.59 | 0.004 sig |
| SECONDARY Time to First Asthma Exacerbation |
231; 319 | — |
| SECONDARY Mean Change From Baseline at Week 52 in Clinic Fractional Exhaled Nitric Oxide (FeNO) (Ppb) |
-17.29; -3.46 | — |
| SECONDARY Mean Change From Baseline in Daily Rescue Medication Use (Weekly Means) at Week 52 |
-2.53; -2.36 | — |
| SECONDARY Mean Change From Baseline in Work Productivity Loss Due to Asthma at Week 52 |
-20.16; -16.58 | — |
| SECONDARY Mean Change From Baseline in Class Productivity Loss Due to Asthma at Week 52 |
-14.03; -24.72 | — |
| SECONDARY Activity Impairment at Week 52 |
-20.0; -17.9 | — |
| SECONDARY Pharmacokinetics of Tezepelumab |
0; 10.1573; 18.7396; 20.1924; 19.5246; 19.8894 | — |
| SECONDARY Mean Change From Baseline at Week 52 in EQ-5D-5L VAS |
14.64; 11.86 | — |
| SECONDARY Clinicians Global Impression of Change at Week 52 |
96; 60; 199; 132; 98; 131 | — |
| SECONDARY Patients Global Impression of Change at Week 52 |
255; 182; 103; 94; 71; 76 | — |
| SECONDARY Patients Global Impression of Severity at Week 52 |
118; 78; 138; 128; 110; 128 | — |
| SECONDARY Mean Change From Baseline at Week 52 in Blood Eosinophils (Cells/uL) |
-170.02; -40.15 | — |
| SECONDARY Mean Change From Baseline at Week 52 in Total Serum IgE (IU/mL) |
-164.38; 43.61 | — |
| SECONDARY Number of Participants With Asthma Specific Healthcare Utilization Over 52 Weeks |
17; 37; 23; 50; 187; 231 | — |
| SECONDARY Mean Change From Baseline in Home Based Morning Peak Expiratory Flow (PEF) at Week 52 (Weekly Means) |
34.57; 18.01 | — |
| SECONDARY Mean Change From Baseline in Home Based Evening Peak Expiratory Flow (PEF) at Week 52 (Weekly Means) |
23.87; 9.01 | — |
| SECONDARY Mean Change From Baseline in Night Time Awakenings (Weekly Means) at Week 52 |
-33.51; -30.22 | — |
| SECONDARY Immunogenecity of Tezepelumab |
26; 44; 17; 25; 14; 8 | — |
| SECONDARY Proportion of Subjects Who Had no Asthma Exacerbations |
54.2; 38.6 | — |
| SECONDARY Annual Asthma Exacerbation Rate Resulting in Emergency Room Visit or Hospitalisation |
0.06; 0.28 | — |
| SECONDARY Proportion of Subjects With at Least One Asthma Exacerbation Associated With Emergency Room Visit or Hospitalisation |
4.7; 12.2 | — |
| SECONDARY Proportion of Subjects Who Had no Asthma Exacerbations Associated With Emergency Room or Hospitalisation |
92.4; 85.1 | — |
Summary
A Multicentre, Randomized, Double-Blind, Placebo Controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Tezepelumab in Adults and Adolescents with Severe Uncontrolled Asthma
Eligibility Criteria
Inclusion Criteria
- Age. 12-80
- Documented physician-diagnosed asthma for at least 12 months
- Subjects who have received a physician-prescribed asthma controller medication with medium or high dose ICS for at least 12 months.
- Documented treatment with a total daily dose of either medium or high dose ICS (≥ 500 µg fluticasone propionate dry powder formulation equivalent total daily dose) for at least 3 months.
- At least one additional maintenance asthma controller medication is required according to standard practice of care and must be documented for at least 3 months.
- Morning pre-BD FEV1 <80% predicted normal (<90% for subjects 12-17 yrs)
- Evidence of asthma as documented by either: Documented historical reversibility of FEV1 ≥12% and ≥200 mL in the previous 12 months OR Post-BD (albuterol/salbutamol) reversibility of FEV1 ≥12% and ≥200 mL during screening.
- Documented history of at least 2 asthma exacerbation events within 12 months.
- ACQ-6 score ≥1.5 at screening and on day of randomization
Exclusion Criteria
- Pulmonary disease other than asthma.
- History of cancer.
- History of a clinically significant infection.
- Current smokers or subjects with smoking history ≥10 pack-years and subjects using vaping products, including electronic cigarettes.
- History of chronic alcohol or drug abuse within 12 months.
- Hepatitis B, C or HIV.
- Pregnant or breastfeeding.
- History of anaphylaxis following any biologic therapy.
- Subject randomized in the current study or previous tezepelumab studies.
Data sourced from ClinicalTrials.gov (NCT03347279). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.