Open-label Study to Assess Reduction of Background Asthma Medication While Sustaining Asthma Control and Clinical Remission With Tezepelumab in Patients 12-80yrs With Severe Asthma.
ARRIVAL
A Multicentre, Randomised, Open-Label, Parallel-Group, Phase IIIb Study to Assess the Potential for Tezepelumab-treated Patients With Severe Asthma to Reduce Background Therapy While Sustaining Asthma Control and Clinical Remission
1 other identifier
interventional
326
12 countries
70
Brief Summary
The objective of this study is to assess the potential for tezepelumab-treated patients (subcutaneous administration) to reduce maintenance therapy without loss of asthma control in adolescent and adults with severe asthma.. Study details include:
- 1.The study duration will be up to 72 weeks.
- 2.The treatment duration will be up to 68 weeks.
- 3.The visit frequency will be once every 4 weeks (Q4W).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Sep 2024
Typical duration for phase_3
70 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 10, 2024
CompletedFirst Posted
Study publicly available on registry
June 25, 2024
CompletedStudy Start
First participant enrolled
September 30, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 25, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 25, 2027
March 12, 2026
March 1, 2026
2.7 years
June 10, 2024
March 11, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Proportion of patients who reduced their SYMBICORT® daily maintenance dose without the loss of asthma control at the end of the step-down phase.
Proportion of patients who reduced their SYMBICORT® daily maintenance dose without the loss of asthma control at the end of the step-down phase to either: Outside of the US: * Medium-dose maintenance and reliever therapy, or * Low-dose maintenance and reliever therapy, or * SYMBICORT® anti-inflammatory reliever only In the US: * Medium-dose SYMBICORT® and AIRSUPRA®,or * Low-dose SYMBICORT® and AIRSUPRA®, or * AIRSUPRA® only
Week 56
Secondary Outcomes (41)
Proportion of patients in asthma control
Week 24
Proportion of patients with characteristics of clinical remission
Week 24
Proportion of patients in asthma control at Week 56 among those in asthma control at Week 24
Week 56
Proportion of patients in asthma control at Week 72 among those in asthma control at Week 24
Week 72
Proportion of patients in asthma control at both Week 56 and Week 72 among those in asthma control at Week 24
Week 56 and Week 72
- +36 more secondary outcomes
Study Arms (3)
Group 1 - Asthma Control or Low Biomarkers - Step-down of ICS
EXPERIMENTALAsthma Control or Low Biomarkers - Step-down of ICS. Only patients with asthma control or low biomarkers at Week 24 will be randomized into Group 1 or 2
Group 2 - Asthma Control or Low Biomarkers - No Step-down of ICS
EXPERIMENTALAsthma Control or Low Biomarkers - No Step-down of ICS. Only patients with asthma control or low biomarkers at Week 24 will be randomized into Group 1 or 2
Group 3 - No Asthma Control or Low Biomarkers - No Step-down of ICS
EXPERIMENTALNo Asthma Control or Low Biomarkers - No Step-down of ICS
Interventions
IMP. Subcutaneous injection. Unit dose strengths 210 mg.
AxMP. Oral inhalation. High-dose: 160 μg/4.5 μg per inhalation; Medium and Low-dose: 80 μg/4.5 μg per inhalation
AxMP. Oral inhalation. Reliever only. Unit dose strengths 90 μg/80 μg per inhalation In US only.
NIMP. Oral nebulization. Unit dose strengths: Graduated doses of 0 mg, 5 mg, 10 mg, 20 mg and 40 mg capsules
AxMP. Used outside the US only. Oral inhalation. Unit dose strengths: 100 μg per inhalation
Eligibility Criteria
You may qualify if:
- Informed Consent
- Provision of signed and dated written ICF prior to any mandatory study-specific procedures, sampling, and analyses for patients who are at or over the age of majority (as per local law). For patients who are less than the age of majority, in addition to providing their informed consent, the patients' legally authorised representative must also provide their informed assent (Appendix A 3).
- Age
- Patients must be 12 to 80 years of age inclusive, at the time of signing the ICF.
- Type of Patient and Disease Characteristics
- Documented medical record history for at least 12 months prior to Visit 1.
- Documented physician-diagnosed severe asthma within 10 years prior to Visit 1 (ie, severe asthma was not diagnosed more than 10 years prior) consisting of any of the following:
- FEV1 \> 12% reversibility, OR
- Evidence of airflow variability (to show that lung function is altered over time): FEV1 ≥ 400 mL variability over time, OR
- Challenge tests that are positive on one of the below:
- (i) Methacholine - PD20 ≤ 8 mg/mL (ii) Mannitol - PD15 15% drop on FEV1 out of dose \< than 635 mg of inhaled mannitol (iii) Exercise - 10% fall of FEV1
- ACQ-5 ≥ 1.5 and \< 3.
- History of physician-diagnosed asthma that requires continuous treatment with high-dose ICS (as defined by GINA or highest approved dose per posology per country) plus a LABA for at least 6 months prior to Visit 1 (Appendix I). The ICS and LABA can be contained within a combination product or given by separate inhalers.
- Note: Additional maintenance asthma controller medications (eg, LTRAs, tiotropium, cromone, theophylline) are allowed.
- Documented history of at least one asthma exacerbation requiring OCS bursts or requiring hospitalization within 12 months prior to Visit 1. An asthma exacerbation will be defined as a worsening of asthma symptoms that leads to any of the following:
- +24 more criteria
You may not qualify if:
- Medical Conditions
- Any clinically important pulmonary disease other than asthma (eg, active lung infection, chronic obstructive pulmonary disease, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia) or pulmonary or systemic diseases, other than asthma, that are associated with elevated peripheral EOS counts (eg, 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, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the investigator and could:
- Affect the safety of the patient throughout the study
- Influence the findings of the study or the interpretation
- Impede the patient's ability to complete the entire duration of study.
- A helminth parasitic infection diagnosed within 6 months prior to Visit 1 that has not been treated with, or has failed to respond to, standard of care therapy.
- Current smokers or patients with smoking history ≥ 10 pack-years and patients 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 prior to Visit 1.
- Tuberculosis requiring treatment within the 12 months prior to Visit 1.
- History of known immunodeficiency disorder including a positive human immunodeficiency virus test at Visit 1, or the patient taking antiretroviral medications as determined by medical history and/or patient's verbal report.
- Major surgery within 8 weeks prior to Visit 1 or planned surgical procedures requiring general anaesthesia or inpatient status for \> 1 day during the conduct of the study.
- Evidence of COVID-19 within 4 weeks prior to screening or ongoing clinically significant COVID-19 sequelae.
- Prior/Concomitant Therapy
- Receipt of any marketed or investigational biologic agent within 4 months or 5 half-lives (whichever is longer) prior to Visit 1 or receipt of any investigational nonbiologic agent within 30 days or 5 half-lives (whichever is longest) prior to Visit 1.
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
- Fortreacollaborator
Study Sites (70)
Research Site
Palmdale, California, 93551, United States
Research Site
Colorado Springs, Colorado, 80907, United States
Research Site
Miami, Florida, 33136, United States
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Boston, Massachusetts, 02115, United States
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St Louis, Missouri, 63110, United States
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New Brunswick, New Jersey, 08901, United States
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Oklahoma City, Oklahoma, 73120, United States
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McAllen, Texas, 78503, United States
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Berazategui, 1104, Argentina
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CABA, C1012AAR, Argentina
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Concepción del Uruguay, 3260, Argentina
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Mendoza, 5500, Argentina
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Mendoza, M5500CCG, Argentina
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Quilmes, B1878FNR, Argentina
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Rosario, 2000, Argentina
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Rosario, 2002, Argentina
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San Miguel de Tucumán, 4000, Argentina
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Santa Fe, 3000, Argentina
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Anderlecht, 1070, Belgium
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Edegem, 2650, Belgium
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Erpent, 5101, Belgium
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Ghent, 9000, Belgium
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Liège, 4000, Belgium
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Haskovo, 6300, Bulgaria
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Pleven, 5804, Bulgaria
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Razgrad, 7200, Bulgaria
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Rousse, 7002, Bulgaria
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Sofia, 1154, Bulgaria
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Sofia, 1431, Bulgaria
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Stara Zagora, 6003, Bulgaria
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Velika Tarnovo, 5250, Bulgaria
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Vancouver, British Columbia, V5Z 1M9, Canada
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Ajax, Ontario, L1S 2J5, Canada
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Windsor, Ontario, N8X 1T3, Canada
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Québec, Quebec, G1V 4G5, Canada
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Sherbrooke, Quebec, J1H 5N4, Canada
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Regina, Saskatchewan, S7N 5A2, Canada
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Aalborg, 9000, Denmark
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Hvidovre, 2650, Denmark
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Svendborg, 5700, Denmark
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Vejle, 7100, Denmark
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Créteil, 94000, France
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La Tronche, 38700, France
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Lyon, 69004, France
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Marseille, 13915, France
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Montpellier, 34295, France
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Strasbourg, 67091, France
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Augsburg, 86150, Germany
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Bonn, 53127, Germany
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Cottbus, 03050, Germany
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Hanover, 30625, Germany
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Mainz, 55128, Germany
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Florence, 50134, Italy
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Orbassano, 10043, Italy
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Roma, 00161, Italy
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Roma, 00168, Italy
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Verona, 37134, Italy
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Chihuahua City, 31200, Mexico
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Cuauhtémoc, 06700, Mexico
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Monterrey, 64360, Mexico
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Badalona(Barcelona), 08916, Spain
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Barcelona, 08035, Spain
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Lugo, 27002, Spain
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Madrid, 28006, Spain
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Madrid, 28040, Spain
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Madrid, 28041, Spain
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Belfast, BT9 7BL, United Kingdom
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Liverpool, L7 8XP, United Kingdom
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London, SE1 9RT, United Kingdom
Research Site
Southampton, SO16 6YD, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 10, 2024
First Posted
June 25, 2024
Study Start
September 30, 2024
Primary Completion (Estimated)
June 25, 2027
Study Completion (Estimated)
June 25, 2027
Last Updated
March 12, 2026
Record last verified: 2026-03
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/PhRMA 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 anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.