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

AstraZeneca

Status and phase: Completed; Phase 3

Conditions: Asthma

Treatments: Biological: Tezepelumab; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03406078

D5180C00009

Details and patient eligibility

About

Phase 3 Study to Evaluate the Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adults with Oral Corticosteroid Dependent Asthma

Full description

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

Enrollment: 150 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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150 participants in 2 patient groups, including a placebo group

Tezepelumab

Experimental group

Description:

Tezepelumab subcutaneous injection

Treatment:

Biological: Tezepelumab

Placebo

Placebo Comparator group

Description:

Placebo subcutaneous injection

Treatment:

Other: Placebo