Clinical trial NCT03406078: Study to Evaluate the Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adults With Oral Corticosteroid Dependent Asthma
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Asthma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2018-01-23
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously
Primary purpose: TREATMENT

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

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

Eligibility 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

Primary outcomes:
measure: Categorized Percent Reduction From Baseline in the Daily OCS Dose While Not Losing Asthma Control
timeFrame: Baseline to Week 48
Secondary outcomes:
measure: Annualised Asthma Exacerbation Rate (AAER)
timeFrame: Baseline to Week 48
measure: Proportion of Subjects With 100% Reduction From Baseline in Daily OCS Dose at Week 48
timeFrame: Baseline to Week 48
measure: Proportion of Subjects With Daily OCS Dose ≤5 mg at Week 48
timeFrame: Week 48
measure: Proportion of Subjects With ≥50% Reduction From Baseline in Daily OCS Dose at Week 48
timeFrame: Baseline to Week 48
measure: Change From Baseline in Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline to Week 48
measure: Change From Baseline in Weekly Mean Daily Asthma Symptom Score Via the Daily Asthma Symptom Diary
timeFrame: Baseline to Week 48
measure: Change From Baseline in Weekly Mean Rescue Medication Use
timeFrame: Baseline to Week 48
measure: Change From Baseline in Weekly Mean Home Peak Expiratory Flow (PEF) (Morning and Evening)
timeFrame: Baseline to Week 48
measure: Change From Baseline in Weekly Mean Number of Night-time Awakening Due to Asthma
timeFrame: Baseline to Week 48
measure: Change From Baseline in Asthma Control Questionnaire 6 (ACQ-6) Score
timeFrame: Baseline to Week 48
measure: Change From Baseline in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(s)+12) Total Score
timeFrame: Baseline to Week 48
measure: Change From Baseline in European Quality of Life - 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L) Score
timeFrame: Baseline to Week 48
measure: Number of Participants With Asthma Specific Resource Utilizations
timeFrame: Baseline to Week 48
measure: Change From Baseline in Work Productivity and Activity Impairment Questionnaire and Classroom Impairment Questionnaire (WPAI+CIQ) Score
timeFrame: Baseline to Week 48
measure: Change From Baseline in FENO
timeFrame: Baseline to Week 48
measure: Change From Baseline in Peripheral Blood Eosinophils
timeFrame: Baseline to Week 48
measure: Change From Baseline From Total Serum IgE
timeFrame: Baseline to Week 48
measure: PK: Serum Trough Concentrations
timeFrame: Pre-dose samples at Baseline, Week 4, Week 12, Week 24, Week 40, Week 48, Week 60
measure: Immunogenicity: Incidence of Anti-drug Antibodies (ADA)
timeFrame: Baseline to Week 60
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Research Site
state: California
city: Newark
country: United States
facility: Research Site
state: Delaware
city: Kissimmee
country: United States
facility: Research Site
state: Florida
city: Kissimmee
country: United States
facility: Research Site
state: Florida
city: Fall River
country: United States
facility: Research Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Bronx
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Greenville
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Toledo
country: United States
facility: Research Site
state: Ohio
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Altoona
country: United States
facility: Research Site
state: Pennsylvania
city: Homestead
country: United States
facility: Research Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Anderson
country: United States
facility: Research Site
state: South Carolina
city: North Charleston
country: United States
facility: Research Site
state: South Carolina
city: McKinney
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Buenos Aires
country: Argentina
facility: Research Site
city: Ciudad de Buenos Aire
country: Argentina
facility: Research Site
city: Córdoba
country: Argentina
facility: Research Site
city: Mendoza
country: Argentina
facility: Research Site
city: Quilmes
country: Argentina
facility: Research Site
city: San Fernando
country: Argentina
facility: Research Site
city: San Miguel de Tucuman
country: Argentina
facility: Research Site
city: Aschaffenburg
country: Germany
facility: Research Site
city: Bamberg
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Koblenz
country: Germany
facility: Research Site
city: Lübeck
country: Germany
facility: Research Site
city: Mainz Am Rhein
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Adana
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Bursa
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Manisa
country: Turkey
facility: Research Site
city: Dnipro
country: Ukraine
facility: Research Site
city: Kherson
country: Ukraine
facility: Research Site
city: Lutsk
country: Ukraine
facility: Research Site
city: Vinnytsia
country: Ukraine
facility: Research Site
Study officials:
References:
citation: Wechsler ME, Menzies-Gow A, Brightling CE, Kuna P, Korn S, Welte T, Griffiths JM, Salapa K, Hellqvist A, Almqvist G, Lal H, Kaur P, Skarby T, Colice G; SOURCE study group. Evaluation of the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma (SOURCE): a randomised, placebo-controlled, phase 3 study. Lancet Respir Med. 2022 Jul;10(7):650-660. doi: 10.1016/S2213-2600(21)00537-3. Epub 2022 Mar 29.
citation: Wechsler ME, Colice G, Griffiths JM, Almqvist G, Skarby T, Piechowiak T, Kaur P, Bowen K, Hellqvist A, Mo M, Garcia Gil E. SOURCE: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma. Respir Res. 2020 Oct 13;21(1):264. doi: 10.1186/s12931-020-01503-z.