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

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ClinicalTrials.gov Identifier: NCT03406078
Recruitment Status : Recruiting
First Posted : January 23, 2018
Last Update Posted : July 6, 2018
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
AstraZeneca

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

Condition or disease Intervention/treatment Phase
Asthma Biological: Tezepelumab Other: Placebo Phase 3

Detailed 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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Double-Blind
Primary Purpose: Treatment
Official 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)
Actual Study Start Date : March 5, 2018
Estimated Primary Completion Date : November 26, 2020
Estimated Study Completion Date : November 26, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma Steroids

Arm Intervention/treatment
Experimental: Tezepelumab
Tezepelumab subcutaneous injection
Biological: Tezepelumab
Tezepelumab subcutaneous injection

Placebo Comparator: Placebo
Placebo subcutaneous injection
Other: Placebo
Placebo subcutaneous injection




Primary Outcome Measures :
  1. Categorized percent reduction from baseline in the daily OCS dose while not losing asthma control. [ Time Frame: Week 48 ]
    Categorized percent reduction from baseline at Week 48. Percent change from baseline is defined as {final dose-baseline dose}/baseline dose)*100, and the categories of percent change from baseline in daily OCS dose are defined as: ≥90% to ≤100% reduction, ≥75% to <90% reduction, ≥50% to <75% reduction, >0% to <50% reduction, and, no change or any increase


Secondary Outcome Measures :
  1. Annualised asthma exacerbation rate (AAER) [ Time Frame: Baseline to Week 48 ]
    The annualized exacerbation rate is based on exacerbations reported by the investigator in the eCRF over 48 weeks

  2. Proportion of subjects with 100% reduction from baseline in daily OCS dose at Week 48 [ Time Frame: Week 48 ]
    Proportion of subjects with 100% reduction from baseline in daily OCS dose at Week 48. Percent change from baseline is defined as {(final dose-baseline dose}/baseline dose)*100.

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

  4. Proportion of subjects with ≥50% reduction from baseline in daily OCS dose at Week 48 [ Time Frame: Week 48 ]
    Proportion of subjects with ≥50% reduction from baseline in daily OCS dose at Week 48. Percent change from baseline is defined as {(final dose-baseline dose}/baseline dose)*100.

  5. Change from baseline in pre-BD forced expiratory volume in 1 second (FEV1) [ Time Frame: Baseline, Week 48 ]
    Change from baseline in FEV1 at Week 48. FEV1 is defined as the volume of air exhaled from the lungs in the first second of a forced expiration.

  6. 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 Asthma Symptom Diary score at Week 48.

  7. Change from baseline in weekly mean rescue medication use [ Time Frame: Baseline, Week 48 ]
    Change from baseline in weekly mean rescue medication use at Week 48. Each timepoint is calculated as weekly means based on daily diary data.

  8. Change from baseline in weekly mean home peak expiratory flow (PEF) (morning and evening) [ Time Frame: Baseline, Week 48 ]
    Change from baseline in weekly mean morning and evening peak expiratory flow (PEF) at Week 48. Home PEF testing will be performed by the subject in the morning upon awakening and in the evening at bedtime using an electronic, hand-held spirometer. Each timepoint is calculated as weekly means.

  9. Change from baseline in weekly mean number of night-time awakening due to asthma [ Time Frame: Baseline, Week 48 ]
    Change from baseline in weekly mean number of night time awakenings at Week 48. Each timepoint is calculated as weekly mean number of awakenings due to asthma based on daily diary data.

  10. Change from baseline in Asthma Control Questionnaire 6 (ACQ-6) score [ Time Frame: Baseline, Week 48 ]
    Change from baseline in ACQ-6 at Week 48. The ACQ-6 captures asthma symptoms and short-acting β2-agonist use via subject-report. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ-6 score is the mean of the responses.

  11. 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 AQLQ(S)+12 as compared to placebo at Week 48. The AQLQ(S)+12 is a questionnaire that measures the health-related quality of life experienced by asthma subjects. The total score is defined as the average of all 32 questions in the AQLQ(S)+12 questionnaire. AQLQ(S)+12 is a 7-point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment).

  12. Change from baseline in European Quality of Life - 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L) score [ Time Frame: Week 48 ]
    EQ-5D at Week 48. The EQ-5D-5L questionnaire assesses 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response options (no problems, slight problems, moderate problems, severe problems, and extreme problems) that reflect increasing levels of difficulty.

  13. Number of asthma specific resource utilizations [ Time Frame: Week 48 ]
    Number of asthma specific resource utilizations (e.g. unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) over 48 weeks

  14. Work Productivity and Activity Impairment Questionnaire and Classroom Impairment Questionnaire (WPAI+CIQ) score [ Time Frame: Week 48 ]
    WPAI+CIQ score at Week 48. The WPAI+CIQ consists of questions about how asthma and asthma related issues impact a subject's ability to work, attend classes, and perform regular daily activities.

  15. Change from baseline in FENO [ Time Frame: Baseline, Week 48 ]
    Change from baseline in fractional exhaled nitric oxide (FeNO) at week 48

  16. Change from baseline in peripheral blood eosinophils [ Time Frame: Baseline, Week 48 ]
    Change from baseline in blood eosinophil counts at week 48

  17. Change from baseline from total IgE [ Time Frame: Baseline, Week 48 ]
    Change from baseline in IgE at week 48

  18. PK: Serum trough concentrations [ Time Frame: Baseline to Week 48 ]
    Serum trough concentrations at each scheduled visit

  19. Immunogenicity: Incidence of anti-drug antibodies (ADA) and neutralizing antibodies (nAb) [ Time Frame: Baseline to Week 48 ]
    Incidence of anti-drug antibodies and neutralizing antibodies over 48 weeks



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. Former smokers with a smoking history of <10 pack years must have stopped for at least 6 months
  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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03406078


Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

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Sponsors and Collaborators
AstraZeneca
Amgen

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03406078     History of Changes
Other Study ID Numbers: D5180C00009
First Posted: January 23, 2018    Key Record Dates
Last Update Posted: July 6, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AstraZeneca:
Asthma

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases