Study to Evaluate the Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adults With Oral Corticosteroid Dependent Asthma

• Register: ClinicalTrials.gov
• Last refreshed on: 21 June 2021
• Main ID: NCT03406078
• Date of registration: 14/01/2018
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca
• Public title: Study to Evaluate the Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adults With Oral Corticosteroid Dependent Asthma SOURCE
• Scientific title: A Multicentre, Randomized, Double-Blind, Placebo Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adults With Oral Corticosteroid Dependent Asthma (SOURCE)
• Date of first enrolment: March 5, 2018
• Target sample size: 150
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03406078
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 3

Countries of recruitment

Argentina, Germany, Korea, Republic of, Poland, Turkey, Ukraine, United States

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Subjects must have received a physician-prescribed medium- or high-dose ICS as per
GINA guideline for at least 12 months

2. Subjects must have received physician prescribed LABA and high dose ICS (total daily
dose >500µg fluticasone propionate dry powder formulation equivalent) for at least 3
months. The ICS and LABA can be parts of a combination product, or given by separate
inhalers.

3. Additional maintenance asthma controller medications are allowed according to standard
practice of care i.e., leukotriene receptor antagonists (LTRAs), theophylline,
long-acting muscarinic antagonists (LAMAs), secondary ICS and cromones. The use of
these medications must be documented for at least 3 months

4. Subjects must have received OCS for the treatment of asthma for at least 6 months
prior to screening and on a stable dose of between = 7.5 to = 30mg (prednisone or
prednisolone equivalent) daily or daily equivalent for at least 1 month. The OCS dose
may be administered every other day (or different doses every other day); Average dose
over two days = The daily dose.

5. Morning pre-bronchodilator (BD) FEV1 must be < 80% predicted normal

6. Subjects must have evidence of asthma as documented by post-BD
(albuterol/salbutatomol) reversibility of FEV1 =12% and =200 mL (15-30 min after
administration of 4 puffs of albuterol/salbutamol), documented either in the previous
12 months

7. Subjects must have a history of at least 1 asthma exacerbation event within 12 months

8. Minimum 10 days compliance with the morning and evening eDiary completion and
OCS,ICS,LABA as well as other asthma controller medications as captured in the eDiary
during the 14 days prior to randomization

9. Documented physician-diagnosed asthma for at least 12 months

Exclusion Criteria:

1. Any clinically important pulmonary disease other than asthma (e.g. active lung
infection, Chronic Obstructive Pulmonary Disease (COPD), bronchiectasis, pulmonary
fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung
cancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia) or ever
diagnosed with pulmonary or systemic disease, other than asthma, that are associated
with elevated peripheral eosinophil counts (e.g. allergic bronchopulmonary
aspergillosis/mycosis, Churg-Strauss syndrome, hypereosinophilic syndrome).

2. Any disorder, including, but not limited to, cardiovascular, gastrointestinal,
hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic,
hematological, psychiatric, or major physical impairment that is not stable in the
opinion of the Investigator and could:

Affect the safety of the subject throughout the study Influence the findings of the
study or the interpretation Impede the subject's ability to complete the entire
duration of study

3. History of cancer: Subjects who have had basal cell carcinoma, localized squamous cell
carcinoma of the skin or in situ carcinoma of the cervix are eligible to participate
in the study provided that curative therapy was completed at least 12 months prior to
visit 1.Subjects who have had other malignancies are eligible provided that curative
therapy was completed at least 5 years

4. A helminth parasitic infection diagnosed within 6 months prior to screening that has
not been treated with, or has failed to respond to, standard of care therapy.

5. Current smokers or subjects with smoking history = 10 pack-years and subjects 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.

6. History of chronic alcohol or drug abuse within 12 months

7. Tuberculosis requiring treatment within the 12 months

8. History of any known immunodeficiency disorder including a positive human
immunodeficiency virus (HIV) test.

9. Major surgery within 8 weeks prior to visit 1 or planned surgical procedures requiring
general anaesthesia or in-subject status for >1 day during the conduct of the study.

10. Clinically significant asthma exacerbation, in the opinion of the Investigator,
including those requiring use of systemic corticosteroids or increase in the
maintenance dose of OCS within 30 days



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Asthma

Intervention(s)

Biological: Tezepelumab

Other: Placebo

Primary Outcome(s)

Categorized percent reduction from baseline in the daily OCS dose while not losing asthma control. [Time Frame: Week 48]

Secondary Outcome(s)

Proportion of subjects with daily OCS dose =5 mg at Week 48 [Time Frame: Week 48]

Annualised asthma exacerbation rate (AAER) [Time Frame: Baseline to Week 48]

Change from baseline from total IgE [Time Frame: Baseline, Week 48]

Change from baseline in Asthma Control Questionnaire 6 (ACQ-6) score [Time Frame: Baseline, Week 48]

Change from baseline in Standardized Asthma Quality of Life Questionnaire for 12 years and older (AQLQ(s)+12) total score [Time Frame: Baseline, Week 48]

Change from baseline in weekly mean home peak expiratory flow (PEF) (morning and evening) [Time Frame: Baseline, Week 48]

Immunogenicity: Incidence of anti-drug antibodies (ADA) [Time Frame: Baseline to Week 48]

Proportion of subjects with 100% reduction from baseline in daily OCS dose at Week 48 [Time Frame: Week 48]

Change from baseline in European Quality of Life - 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L) score [Time Frame: Week 48]

Change from baseline in peripheral blood eosinophils [Time Frame: Baseline, Week 48]

Change from baseline in weekly mean number of night-time awakening due to asthma [Time Frame: Baseline, Week 48]

Change from baseline in pre-BD forced expiratory volume in 1 second (FEV1) [Time Frame: Baseline, Week 48]

Proportion of subjects with =50% reduction from baseline in daily OCS dose at Week 48 [Time Frame: Week 48]

Change from baseline in weekly mean rescue medication use [Time Frame: Baseline, Week 48]

Change from baseline in Weekly mean daily Asthma Symptom Score via the daily Asthma Symptom Diary [Time Frame: Baseline, Week 48]

Change from baseline in FENO [Time Frame: Baseline, Week 48]

Number of asthma specific resource utilizations [Time Frame: Week 48]

Work Productivity and Activity Impairment Questionnaire and Classroom Impairment Questionnaire (WPAI+CIQ) score [Time Frame: Week 48]

PK: Serum trough concentrations [Time Frame: Baseline to Week 48]

Secondary ID(s)

D5180C00009

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Amgen