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

NCT03406078 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: D5180C00009
• Study Type: interventional
• Target: 150
• Locations: 7 countries
• Sites: 60

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

Conditions

Asthma

Keywords

Asthma

Outcome Measures

Primary Outcomes (1)

• Categorized Percent Reduction From Baseline in the Daily OCS Dose While Not Losing Asthma Control

  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.

  Baseline to Week 48

Secondary Outcomes (19)

• Annualised Asthma Exacerbation Rate (AAER)

  Baseline to Week 48

• Proportion of Subjects With 100% Reduction From Baseline in Daily OCS Dose at Week 48

  Baseline to Week 48

• Proportion of Subjects With Daily OCS Dose ≤5 mg at Week 48

  Week 48

• Proportion of Subjects With ≥50% Reduction From Baseline in Daily OCS Dose at Week 48

  Baseline to Week 48

• Change From Baseline in Pre-bronchodilator (Pre-BD) Forced Expiratory Volume in 1 Second (FEV1)

  Baseline to Week 48

Study Arms (2)

Tezepelumab

EXPERIMENTAL

Tezepelumab subcutaneous injection

Biological: Tezepelumab

Placebo

PLACEBO COMPARATOR

Placebo subcutaneous injection

Other: Placebo

Interventions

Tezepelumab BIOLOGICAL

Tezepelumab subcutaneous injection

Tezepelumab

Placebo OTHER

Placebo subcutaneous injection

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have received a physician-prescribed medium- or high-dose ICS as per GINA guideline for at least 12 months
• 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.
• 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
• 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.
• Morning pre-bronchodilator (BD) FEV1 must be \< 80% predicted normal
• 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
• Subjects must have a history of at least 1 asthma exacerbation event within 12 months
• 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
• Documented physician-diagnosed asthma for at least 12 months

You may not qualify if:

• 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).
• 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
• 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
• 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.
• 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.
• History of chronic alcohol or drug abuse within 12 months
• Tuberculosis requiring treatment within the 12 months
• History of any known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.
• 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.
• 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

Sponsors & Collaborators

• AstraZeneca: lead
• Amgen: collaborator

Study Sites (60)

Research Site

Bakersfield, California, 93301, United States

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Newark, Delaware, 19713, United States

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Kissimmee, Florida, 34741, United States

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Kissimmee, Florida, 34746, United States

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Fall River, Massachusetts, 02721, United States

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Ann Arbor, Michigan, 48109, United States

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St Louis, Missouri, 63141, United States

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The Bronx, New York, 10461, United States

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Durham, North Carolina, 27705, United States

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Greenville, North Carolina, 27834, United States

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Cincinnati, Ohio, 45231, United States

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Cleveland, Ohio, 44130, United States

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Toledo, Ohio, 43617, United States

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Oklahoma City, Oklahoma, 73109, United States

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Altoona, Pennsylvania, 16602, United States

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Homestead, Pennsylvania, 15120, United States

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Philadelphia, Pennsylvania, 19140, United States

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Anderson, South Carolina, 29621, United States

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North Charleston, South Carolina, 29406, United States

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McKinney, Texas, 75069, United States

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San Antonio, Texas, 78251, United States

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Buenos Aires, C1414AIF, Argentina

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Ciudad de Buenos Aire, C1425BEN, Argentina

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Córdoba, X5003DCE, Argentina

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Mendoza, 5500, Argentina

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Quilmes, B1878FNR, Argentina

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San Fernando, 1646, Argentina

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San Miguel de Tucumán, T4000IAR, Argentina

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Aschaffenburg, 63739, Germany

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Bamberg, 96049, Germany

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Berlin, 10367, Germany

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Berlin, 10717, Germany

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Berlin, 10969, Germany

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Hamburg, 22299, Germany

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Hanover, 30625, Germany

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Hanover, D-30173, Germany

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Koblenz, 56068, Germany

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Lübeck, 23552, Germany

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Mainz Am Rhein, 55131, Germany

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München, 81377, Germany

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Krakow, 31-559, Poland

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Lodz, 90-153, Poland

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Wroclaw, 53-301, Poland

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Daegu, 42415, South Korea

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Seoul, 03082, South Korea

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Seoul, 03312, South Korea

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Seoul, 03722, South Korea

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Seoul, 05505, South Korea

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Seoul, 06351, South Korea

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Seoul, 06591, South Korea

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Adana, 01330, Turkey (Türkiye)

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Ankara, 06230, Turkey (Türkiye)

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Ankara, 06280, Turkey (Türkiye)

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Bursa, 16059, Turkey (Türkiye)

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Istanbul, 34098, Turkey (Türkiye)

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Manisa, 45030, Turkey (Türkiye)

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Dnipro, 49007, Ukraine

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Kherson, 73000, Ukraine

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Lutsk, 4300, Ukraine

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Vinnytsia, 21029, Ukraine

Location

Related Publications (3)

• Menzies-Gow A, Wechsler ME, Brightling CE, Korn S, Corren J, Israel E, Chupp G, Bednarczyk A, Ponnarambil S, Caveney S, Almqvist G, Golabek M, Simonsson L, Lawson K, Bowen K, Colice G; DESTINATION study investigators. Long-term safety and efficacy of tezepelumab in people with severe, uncontrolled asthma (DESTINATION): a randomised, placebo-controlled extension study. Lancet Respir Med. 2023 May;11(5):425-438. doi: 10.1016/S2213-2600(22)00492-1. Epub 2023 Jan 23.

  PMID: 36702146 DERIVED

• 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.

  PMID: 35364018 DERIVED

• 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.

  PMID: 33050928 DERIVED

Related Links

• CSP redacted
• SAP redacted

MeSH Terms

Conditions

Asthma

Interventions

tezepelumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Global Clinical Head
• Organization: AstraZeneca

information.center@astrazeneca.com

+1 302 885 1180

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously

Study Record Dates

• First Submitted: January 14, 2018
• First Posted: January 23, 2018
• Study Start: March 5, 2018
• Primary Completion: September 25, 2020
• Study Completion: September 25, 2020
• Last Updated: December 9, 2021
• Results First Posted: December 9, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

DE (12); TU (6); UA (4); AR (7); US (21); KR (7); PL (3)