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.
NCT ID: NCT06473779
Last Updated: 2025-11-13
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE3
300 participants
INTERVENTIONAL
2024-09-30
2027-06-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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).
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Approximately 65 sites in 10 countries will enrol adult and adolescent patients with severe uncontrolled asthma.
The study is divided into 5 phases as described below:
* Screening/Run-in Phase (from Week -4 until Week 0, up to 4 Weeks)
* Treatment Induction Phase (Week 0 to Week 4)
* Treatment Continuation Phase (Week 4 to Week 24)
* Tezepelumab Treatment With or Without ICS Step-down Therapy Phase (Week 24 to Week 56)
* Maintenance Phase (Week 56 to Week 72)
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Group 1 - Asthma Control or Low Biomarkers - Step-down of ICS
Asthma 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
Tezepelumab
IMP. Subcutaneous injection. Unit dose strengths 210 mg.
Budesonide/formoterol
AxMP. Oral inhalation. High-dose: 160 μg/4.5 μg per inhalation; Medium and Low-dose: 80 μg/4.5 μg per inhalation
Albuterol/budesonide (AIRSUPRA®)
AxMP. Oral inhalation. Reliever only. Unit dose strengths 90 μg/80 μg per inhalation In US only.
Mannitol
NIMP. Oral nebulization. Unit dose strengths: Graduated doses of 0 mg, 5 mg, 10 mg, 20 mg and 40 mg capsules
Salbutamol
AxMP. Used outside the US only. Oral inhalation. Unit dose strengths: 100 μg per inhalation
Group 2 - Asthma Control or Low Biomarkers - No Step-down of ICS
Asthma 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
Tezepelumab
IMP. Subcutaneous injection. Unit dose strengths 210 mg.
Budesonide/formoterol
AxMP. Oral inhalation. High-dose: 160 μg/4.5 μg per inhalation; Medium and Low-dose: 80 μg/4.5 μg per inhalation
Albuterol/budesonide (AIRSUPRA®)
AxMP. Oral inhalation. Reliever only. Unit dose strengths 90 μg/80 μg per inhalation In US only.
Mannitol
NIMP. Oral nebulization. Unit dose strengths: Graduated doses of 0 mg, 5 mg, 10 mg, 20 mg and 40 mg capsules
Salbutamol
AxMP. Used outside the US only. Oral inhalation. Unit dose strengths: 100 μg per inhalation
Group 3 - No Asthma Control or Low Biomarkers - No Step-down of ICS
No Asthma Control or Low Biomarkers - No Step-down of ICS
Tezepelumab
IMP. Subcutaneous injection. Unit dose strengths 210 mg.
Budesonide/formoterol
AxMP. Oral inhalation. High-dose: 160 μg/4.5 μg per inhalation; Medium and Low-dose: 80 μg/4.5 μg per inhalation
Albuterol/budesonide (AIRSUPRA®)
AxMP. Oral inhalation. Reliever only. Unit dose strengths 90 μg/80 μg per inhalation In US only.
Mannitol
NIMP. Oral nebulization. Unit dose strengths: Graduated doses of 0 mg, 5 mg, 10 mg, 20 mg and 40 mg capsules
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Tezepelumab
IMP. Subcutaneous injection. Unit dose strengths 210 mg.
Budesonide/formoterol
AxMP. Oral inhalation. High-dose: 160 μg/4.5 μg per inhalation; Medium and Low-dose: 80 μg/4.5 μg per inhalation
Albuterol/budesonide (AIRSUPRA®)
AxMP. Oral inhalation. Reliever only. Unit dose strengths 90 μg/80 μg per inhalation In US only.
Mannitol
NIMP. Oral nebulization. Unit dose strengths: Graduated doses of 0 mg, 5 mg, 10 mg, 20 mg and 40 mg capsules
Salbutamol
AxMP. Used outside the US only. Oral inhalation. Unit dose strengths: 100 μg per inhalation
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
1. 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
2. Patients must be 12 to 80 years of age inclusive, at the time of signing the ICF.
Type of Patient and Disease Characteristics
3. Documented medical record history for at least 12 months prior to Visit 1.
4. 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:
1. FEV1 \> 12% reversibility, OR
2. Evidence of airflow variability (to show that lung function is altered over time): FEV1 ≥ 400 mL variability over time, OR
3. 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
5. ACQ-5 ≥ 1.5 and \< 3.
6. 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.
7. Pre-brochodilator FEV1 \> 60% predicted and evidence of FEV1 reversibility of \> 12% within 6 months prior to screening or at screening. Patients with normal lung function (FEV1 \> 80%) need evidence of airflow variability as per inclusion criterion 4.
8. 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:
1. A temporary bolus/burst of systemic corticosteroids for at least 3 consecutive days to treat symptoms of asthma worsening; a single depo-injectable dose of corticosteroids will be considered equivalent to a 3-day bolus/burst of systemic corticosteroids
2. Or, an ER visit (defined as evaluation and treatment for \< 24 hours in ER) due to asthma that required systemic corticosteroids (as per above)
3. Or, an in-patient hospitalisation (defined as admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for ≥ 24 hours).
Sex and Contraceptive/Barrier Requirements
9. Male or female.
Female patients:
* Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Women of nonchildbearing potential are defined as women who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrhoeic for 12 months prior to the planned start date of the induction phase without an alternative medical cause.
* The following age-specific requirements apply:
* Women \< 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and follicle-stimulating hormone levels in the postmenopausal range.
* Women ≥ 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment.
* Adolescents: if patient is female and has reached menarche or has reached Tanner stage 3 breast development (even if not having reached menarche), the patient will be considered a WOCBP.
10. WOCBP must be willing to use one of the methods of contraception described hereafter, from the time of signing the ICF throughout the study and 16 weeks after last tezepelumab administration:
* Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal
* Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable
* Intrauterine device
* Intrauterine hormone-releasing system
* Bilateral tubal occlusion
* Vasectomised partner (vasectomised partner is a highly effective birth control method provided that the partner is the sole sexual partner of the WOCBP patient and that the vasectomised partner has received medical assessment of the surgical success)
* Sexual abstinence: it is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the patient.
* Cessation of contraception after this point should be discussed with a responsible physician
Before dosing with tezepelumab at Week 0, patients should fulfil the following criteria:
11. ACQ-5 ≥ 1.5 and \< 3.
12. Demonstrated proper inhaler technique (patients with improper technique at screening may be trained during screening, but must demonstrate proper technique before enrollment).
13. No excessive SABA use (should be \< 5 puffs/day) or for patients using SMART therapy outside the US, no excessive use of SYMBICORT (should be ≤ 8 inhalations/day) or for US patients, no excessive use of AIRSUPRA (should be ≤ 12 inhalations/day).
Exclusion Criteria
1. 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).
2. 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.
3. 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.
4. 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.
5. History of chronic alcohol or drug abuse within 12 months prior to Visit 1.
6. Tuberculosis requiring treatment within the 12 months prior to Visit 1.
7. 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.
8. 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.
9. Evidence of COVID-19 within 4 weeks prior to screening or ongoing clinically significant COVID-19 sequelae.
Prior/Concomitant Therapy
10. 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.
11. OCS-dependent patients (received chronic OCS therapy \[prednisone ≥ 5 mg/day or equivalent\]) for at least 3 months preceding Visit 1.
12. Daily use of maintenance corticosteroids for any reason.
13. Treatment with systemic immunosuppressive/immunomodulating drugs (eg, methotrexate, cyclosporine, etc.), except for OCS used in the treatment of asthma/asthma exacerbations, within the last 12 weeks or 5 half-lives (whichever is longer) prior to Visit 1.
14. Receipt of immunoglobulin or blood products within 30 days prior to Visit 1.
15. Receipt of live attenuated vaccines 30 days prior to the date of Visit 1 and during the study.
16. Patients that have been treated with bronchial thermoplasty in the last 12 months prior to Visit 1.
Prior/Concurrent Clinical Study Experience
17. Known history of sensitivity to any component of the tezepelumab formulation or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.
18. History of anaphylaxis or documented immune complex disease (Type III hypersensitivity reactions) following any biologic therapy.
19. Concurrent enrolment in another clinical study involving an IMP.
Diagnostic Assessments
20. Any clinically meaningful abnormal finding in physical examination, haematology, clinical chemistry at Visit 1 which, in the opinion of the investigator, may put the patient at risk because of his/her participation in the study, or may influence the results of the study, or the patient's ability to complete the entire duration of the study.
21. Evidence of active liver disease, including jaundice or AST, ALT, or ALP \> 2 times the ULN at Visit 1.
22. Positive hepatitis B surface antigen, hepatitis C virus antibody serology at screening, or a positive medical history for hepatitis B or C. Patients with a history of hepatitis B vaccination without a history of hepatitis B are allowed to participate.
Other Exclusions
23. Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff and/or site staff), or patients employed by or relatives of the employees of the site or AstraZeneca.
24. Judgement by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
25. For women only: Pregnant, breastfeeding, or lactating women. A serum β-HCG pregnancy test must be drawn for WOCBP at the screening visit. If the results of the serum β-HCG cannot be obtained prior to dosing of the IMP, a patient may be enrolled on the basis of a negative urine pregnancy test, though serum β-HCG must still be obtained. If either test is positive, the patient should be excluded. Since urine and serum tests may miss a pregnancy in the first days after conception, relevant menstrual history and sexual history, including methods of contraception, should be considered. Any patient whose menstrual and/or sexual history suggests the possibility of early pregnancy should be excluded.
12 Years
80 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Fortrea
INDUSTRY
AstraZeneca
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Research Site
Palmdale, California, United States
Research Site
Colorado Springs, Colorado, United States
Research Site
Miami, Florida, United States
Research Site
Hyattsville, Maryland, United States
Research Site
Boston, Massachusetts, United States
Research Site
St Louis, Missouri, United States
Research Site
New Brunswick, New Jersey, United States
Research Site
Oklahoma City, Oklahoma, United States
Research Site
McAllen, Texas, United States
Research Site
Berazategui, , Argentina
Research Site
CABA, , Argentina
Research Site
Concepción del Uruguay, , Argentina
Research Site
Mendoza, , Argentina
Research Site
Mendoza, , Argentina
Research Site
Quilmes, , Argentina
Research Site
Rosario, , Argentina
Research Site
Rosario, , Argentina
Research Site
San Miguel de Tucumán, , Argentina
Research Site
Santa Fe, , Argentina
Research Site
Anderlecht, , Belgium
Research Site
Edegem, , Belgium
Research Site
Erpent, , Belgium
Research Site
Ghent, , Belgium
Research Site
Liège, , Belgium
Research Site
Haskovo, , Bulgaria
Research Site
Kozloduy, , Bulgaria
Research Site
Pleven, , Bulgaria
Research Site
Razgrad, , Bulgaria
Research Site
Rousse, , Bulgaria
Research Site
Sofia, , Bulgaria
Research Site
Sofia, , Bulgaria
Research Site
Stara Zagora, , Bulgaria
Research Site
Stara Zagora, , Bulgaria
Research Site
Velika Tarnovo, , Bulgaria
Research Site
Edmonton, Alberta, Canada
Research Site
Vancouver, British Columbia, Canada
Research Site
Ajax, Ontario, Canada
Research Site
Windsor, Ontario, Canada
Research Site
Québec, Quebec, Canada
Research Site
Sherbrooke, Quebec, Canada
Research Site
Regina, Saskatchewan, Canada
Research Site
Aalborg, , Denmark
Research Site
Hvidovre, , Denmark
Research Site
Svendborg, , Denmark
Research Site
Vejle, , Denmark
Research Site
Bordeaux, , France
Research Site
Créteil, , France
Research Site
La Tronche, , France
Research Site
Lyon, , France
Research Site
Marseille, , France
Research Site
Montpellier, , France
Research Site
Strasbourg, , France
Research Site
Augsburg, , Germany
Research Site
Bonn, , Germany
Research Site
Cottbus, , Germany
Research Site
Hamburg, , Germany
Research Site
Hanover, , Germany
Research Site
Mainz, , Germany
Research Site
München, , Germany
Research Site
Cagliari, , Italy
Research Site
Catania, , Italy
Research Site
Florence, , Italy
Research Site
Orbassano, , Italy
Research Site
Roma, , Italy
Research Site
Roma, , Italy
Research Site
Salerno, , Italy
Research Site
Verona, , Italy
Research Site
Chihuahua City, , Mexico
Research Site
Cuauhtémoc, , Mexico
Research Site
Guadalajara, , Mexico
Research Site
Monterrey, , Mexico
Research Site
Monterrey, , Mexico
Research Site
Veracruz, , Mexico
Research Site
Badalona(Barcelona), , Spain
Research Site
Barcelona, , Spain
Research Site
Lugo, , Spain
Research Site
Madrid, , Spain
Research Site
Madrid, , Spain
Research Site
Madrid, , Spain
Research Site
Oviedo, , Spain
Research Site
Pamplona, , Spain
Research Site
Belfast, , United Kingdom
Research Site
Liverpool, , United Kingdom
Research Site
London, , United Kingdom
Research Site
Southampton, , United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
AstraZeneca Clinical Study Information Center
Role: CONTACT
Phone: 1-877-240-9479
Email: [email protected]
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
D5180C00047
Identifier Type: -
Identifier Source: org_study_id