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.

Last updated: June 16, 2025
Sponsor: AstraZeneca
Overall Status: Active - Recruiting

Phase

3

Condition

Asthma

Treatment

Albuterol/budesonide (AIRSUPRA®)

Mannitol

Salbutamol

Clinical Study ID

NCT06473779
D5180C00047
  • Ages 12-80
  • All Genders

Study 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).

Eligibility Criteria

Inclusion

Inclusion Criteria at Visit 1 (Screening):

Informed Consent

  1. Provision of signed and dated written ICF prior to any mandatory study-specificprocedures, sampling, and analyses for patients who are at or over the age ofmajority (as per local law). For patients who are less than the age of majority, inaddition to providing their informed consent, the patients' legally authorisedrepresentative 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 thefollowing:

  5. FEV1 > 12% reversibility, OR

  6. Evidence of airflow variability (to show that lung function is altered overtime): FEV1 ≥ 400 mL variability over time, OR

  7. 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

  1. ACQ-5 ≥ 1.5 and < 3.

  2. History of physician-diagnosed asthma that requires continuous treatment withhigh-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 LABAcan be contained within a combination product or given by separate inhalers. Note: Additional maintenance asthma controller medications (eg, LTRAs, tiotropium,cromone, theophylline) are allowed.

  3. Pre-brochodilator FEV1 > 60% predicted and evidence of FEV1 reversibility of > 12%within 6 months prior to screening or at screening. Patients with normal lungfunction (FEV1 > 80%) need evidence of airflow variability as per inclusioncriterion 4.

  4. Documented history of at least one asthma exacerbation requiring OCS bursts orrequiring hospitalization within 12 months prior to Visit 1. An asthma exacerbationwill be defined as a worsening of asthma symptoms that leads to any of thefollowing:

  5. A temporary bolus/burst of systemic corticosteroids for at least 3 consecutivedays to treat symptoms of asthma worsening; a single depo-injectable dose ofcorticosteroids will be considered equivalent to a 3-day bolus/burst ofsystemic corticosteroids

  6. Or, an ER visit (defined as evaluation and treatment for < 24 hours in ER) dueto asthma that required systemic corticosteroids (as per above)

  7. Or, an in-patient hospitalisation (defined as admission to an inpatientfacility and/or evaluation and treatment in a healthcare facility for ≥ 24hours). Sex and Contraceptive/Barrier Requirements

  8. Male or female. Female patients:

  • Contraceptive use by women should be consistent with local regulationsregarding the methods of contraception for those participating in clinicalstudies. Women of nonchildbearing potential are defined as women who are eitherpermanently sterilised (hysterectomy, bilateral oophorectomy, or bilateralsalpingectomy) or who are postmenopausal. Women will be consideredpostmenopausal if they have been amenorrhoeic for 12 months prior to theplanned 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 beenamenorrhoeic for 12 months or more following cessation of exogenoushormonal treatment and follicle-stimulating hormone levels in thepostmenopausal range.

  • Women ≥ 50 years old would be considered postmenopausal if they have beenamenorrhoeic for 12 months or more following cessation of all exogenoushormonal treatment.

  • Adolescents: if patient is female and has reached menarche or has reachedTanner stage 3 breast development (even if not having reached menarche),the patient will be considered a WOCBP.

  1. WOCBP must be willing to use one of the methods of contraception describedhereafter, from the time of signing the ICF throughout the study and 16 weeks afterlast tezepelumab administration:
  • Combined (oestrogen and progestogen containing) hormonal contraceptionassociated with inhibition of ovulation: oral, intravaginal, transdermal

  • Progestogen-only hormonal contraception associated with inhibition ofovulation: oral, injectable, implantable

  • Intrauterine device

  • Intrauterine hormone-releasing system

  • Bilateral tubal occlusion

  • Vasectomised partner (vasectomised partner is a highly effective birth controlmethod provided that the partner is the sole sexual partner of the WOCBPpatient and that the vasectomised partner has received medical assessment ofthe surgical success)

  • Sexual abstinence: it is considered a highly effective method only if definedas refraining from heterosexual intercourse during the entire period of riskassociated with the study treatments. The reliability of sexual abstinenceneeds to be evaluated in relation to the duration of the study and thepreferred and usual lifestyle of the patient.

  • Cessation of contraception after this point should be discussed with aresponsible physician Inclusion Criteria 5.1.2 Treatment Induction Phase at Visit 2 (Week 0): Before dosing with tezepelumab at Week 0, patients should fulfil the followingcriteria:

  1. ACQ-5 ≥ 1.5 and < 3.

  2. Demonstrated proper inhaler technique (patients with improper technique at screeningmay be trained during screening, but must demonstrate proper technique beforeenrollment).

  3. No excessive SABA use (should be < 5 puffs/day) or for patients using SMART therapyoutside the US, no excessive use of SYMBICORT (should be ≤ 8 inhalations/day) or forUS patients, no excessive use of AIRSUPRA (should be ≤ 12 inhalations/day).

Exclusion

Exclusion Criteria:

Medical Conditions

  1. Any clinically important pulmonary disease other than asthma (eg, active lunginfection, chronic obstructive pulmonary disease, bronchiectasis, pulmonaryfibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lungcancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia) orpulmonary or systemic diseases, other than asthma, that are associated with elevatedperipheral 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 theopinion 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.

  1. A helminth parasitic infection diagnosed within 6 months prior to Visit 1 that hasnot been treated with, or has failed to respond to, standard of care therapy.

  2. Current smokers or patients with smoking history ≥ 10 pack-years and patients usingvaping products, including electronic cigarettes. Former smokers with a smokinghistory of < 10 pack-years and users of vaping or e-cigarette products must havestopped for at least 6 months prior to Visit 1 to be eligible.

  3. History of chronic alcohol or drug abuse within 12 months prior to Visit 1.

  4. Tuberculosis requiring treatment within the 12 months prior to Visit 1.

  5. History of known immunodeficiency disorder including a positive humanimmunodeficiency virus test at Visit 1, or the patient taking antiretroviralmedications as determined by medical history and/or patient's verbal report.

  6. Major surgery within 8 weeks prior to Visit 1 or planned surgical proceduresrequiring general anaesthesia or inpatient status for > 1 day during the conduct ofthe study.

  7. Evidence of COVID-19 within 4 weeks prior to screening or ongoing clinicallysignificant COVID-19 sequelae. Prior/Concomitant Therapy

  8. Receipt of any marketed or investigational biologic agent within 4 months or 5half-lives (whichever is longer) prior to Visit 1 or receipt of any investigationalnonbiologic agent within 30 days or 5 half-lives (whichever is longest) prior toVisit 1.

  9. OCS-dependent patients (received chronic OCS therapy [prednisone ≥ 5 mg/day orequivalent]) for at least 3 months preceding Visit 1.

  10. Daily use of maintenance corticosteroids for any reason.

  11. Treatment with systemic immunosuppressive/immunomodulating drugs (eg, methotrexate,cyclosporine, etc.), except for OCS used in the treatment of asthma/asthmaexacerbations, within the last 12 weeks or 5 half-lives (whichever is longer) priorto Visit 1.

  12. Receipt of immunoglobulin or blood products within 30 days prior to Visit 1.

  13. Receipt of live attenuated vaccines 30 days prior to the date of Visit 1 and duringthe study.

  14. Patients that have been treated with bronchial thermoplasty in the last 12 monthsprior to Visit 1. Prior/Concurrent Clinical Study Experience

  15. Known history of sensitivity to any component of the tezepelumab formulation or ahistory of drug or other allergy that, in the opinion of the investigator or medicalmonitor, contraindicates their participation.

  16. History of anaphylaxis or documented immune complex disease (Type IIIhypersensitivity reactions) following any biologic therapy.

  17. Concurrent enrolment in another clinical study involving an IMP. Diagnostic Assessments

  18. Any clinically meaningful abnormal finding in physical examination, haematology,clinical chemistry at Visit 1 which, in the opinion of the investigator, may put thepatient at risk because of his/her participation in the study, or may influence theresults of the study, or the patient's ability to complete the entire duration ofthe study.

  19. Evidence of active liver disease, including jaundice or AST, ALT, or ALP > 2 timesthe ULN at Visit 1.

  20. Positive hepatitis B surface antigen, hepatitis C virus antibody serology atscreening, or a positive medical history for hepatitis B or C. Patients with ahistory of hepatitis B vaccination without a history of hepatitis B are allowed toparticipate. Other Exclusions

  21. Involvement in the planning and/or conduct of the study (applies to AstraZenecastaff and/or site staff), or patients employed by or relatives of the employees ofthe site or AstraZeneca.

  22. Judgement by the investigator that the patient should not participate in the studyif the patient is unlikely to comply with study procedures, restrictions, andrequirements.

  23. For women only: Pregnant, breastfeeding, or lactating women. A serum β-HCG pregnancytest 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 onthe basis of a negative urine pregnancy test, though serum β-HCG must still beobtained. If either test is positive, the patient should be excluded. Since urineand serum tests may miss a pregnancy in the first days after conception, relevantmenstrual history and sexual history, including methods of contraception, should beconsidered. Any patient whose menstrual and/or sexual history suggests thepossibility of early pregnancy should be excluded.

Study Design

Total Participants: 300
Treatment Group(s): 5
Primary Treatment: Albuterol/budesonide (AIRSUPRA®)
Phase: 3
Study Start date:
September 30, 2024
Estimated Completion Date:
June 30, 2027

Study Description

This is a multicentre, randomised, open-label, parallel-group, phase IIIb study to assess the potential for tezepelumab-treated patients to (1) reduce maintenance therapy without the loss of asthma control at Week 56, among those who demonstrated asthma control or low biomarkers at Week 24, and (2) be in asthma control and have characteristics of clinical remission at Week 24.

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

  • Maintenance Phase (Week 56 to Week 72)

Connect with a study center

  • Research Site

    Berazategui, 1104
    Argentina

    Site Not Available

  • Research Site

    Caba, C1012AAR
    Argentina

    Active - Recruiting

  • Research Site

    Concepción del Uruguay, 3260
    Argentina

    Active - Recruiting

  • Research Site

    Mendoza, M5500CCG
    Argentina

    Site Not Available

  • Research Site

    Quilmes, B1878FNR
    Argentina

    Site Not Available

  • Research Site

    Rosario, 2002
    Argentina

    Site Not Available

  • Research Site

    San Miguel de Tucuman, 4000
    Argentina

    Active - Recruiting

  • Research Site

    Santa Fe, 3000
    Argentina

    Site Not Available

  • Research Site

    Anderlecht, 1070
    Belgium

    Active - Recruiting

  • Research Site

    Edegem, 2650
    Belgium

    Active - Recruiting

  • Research Site

    Erpent, 5101
    Belgium

    Active - Recruiting

  • Research Site

    Gent, 9000
    Belgium

    Active - Recruiting

  • Research Site

    Liège, 4000
    Belgium

    Active - Recruiting

  • Research Site

    Haskovo, 6300
    Bulgaria

    Active - Recruiting

  • Research Site

    Kozloduy, 3320
    Bulgaria

    Site Not Available

  • Research Site

    Pleven, 5804
    Bulgaria

    Active - Recruiting

  • Research Site

    Razgrad, 7200
    Bulgaria

    Active - Recruiting

  • Research Site

    Ruse, 7002
    Bulgaria

    Active - Recruiting

  • Research Site

    Sofia, 1154
    Bulgaria

    Active - Recruiting

  • Research Site

    Stara Zagora, 6000
    Bulgaria

    Site Not Available

  • Research Site

    Velika Tarnovo, 5250
    Bulgaria

    Active - Recruiting

  • Research Site

    Edmonton, Alberta T6G 2B7
    Canada

    Site Not Available

  • Research Site

    Vancouver, British Columbia V5Z 1M9
    Canada

    Active - Recruiting

  • Research Site

    Ajax, Ontario L1S 2J5
    Canada

    Active - Recruiting

  • Research Site

    Windsor, Ontario N8X 1T3
    Canada

    Active - Recruiting

  • Research Site

    Sherbrooke, Quebec J1H 5N4
    Canada

    Active - Recruiting

  • Research Site

    Regina, Saskatchewan S7N 5A2
    Canada

    Active - Recruiting

  • Research Site

    Quebec, G1V 4G5
    Canada

    Active - Recruiting

  • Research Site

    Aalborg, 9000
    Denmark

    Active - Recruiting

  • Research Site

    Hvidovre, 2650
    Denmark

    Active - Recruiting

  • Research Site

    Svendborg, 5700
    Denmark

    Active - Recruiting

  • Research Site

    Vejle, 7100
    Denmark

    Active - Recruiting

  • Research Site

    Bordeaux, 33076
    France

    Active - Recruiting

  • Research Site

    Créteil, 94000
    France

    Active - Recruiting

  • Research Site

    La Tronche, 38700
    France

    Active - Recruiting

  • Research Site

    Lyon, 69004
    France

    Active - Recruiting

  • Research Site

    Marseille, 13915
    France

    Active - Recruiting

  • Research Site

    Montpellier, 34295
    France

    Active - Recruiting

  • Research Site

    Strasbourg, 67091
    France

    Active - Recruiting

  • Research Site

    Augsburg, 86150
    Germany

    Active - Recruiting

  • Research Site

    Bonn, 53127
    Germany

    Site Not Available

  • Research Site

    Cottbus, 03050
    Germany

    Active - Recruiting

  • Research Site

    Hamburg, 20354
    Germany

    Active - Recruiting

  • Research Site

    Hannover, 30625
    Germany

    Active - Recruiting

  • Research Site

    Mainz, 55128
    Germany

    Active - Recruiting

  • Research Site

    München, 81377
    Germany

    Site Not Available

  • Research Site

    Cagliari, 09122
    Italy

    Active - Recruiting

  • Research Site

    Catania, 95123
    Italy

    Active - Recruiting

  • Research Site

    Firenze, 50134
    Italy

    Active - Recruiting

  • Research Site

    Orbassano, 10043
    Italy

    Active - Recruiting

  • Research Site

    Roma, 00168
    Italy

    Active - Recruiting

  • Research Site

    Salerno, 84131
    Italy

    Active - Recruiting

  • Research Site

    Verona, 37134
    Italy

    Active - Recruiting

  • Research Site

    Chihuahua, 31200
    Mexico

    Site Not Available

  • Research Site

    Cuauhtémoc, 06700
    Mexico

    Site Not Available

  • Research Site

    Guadalajara, 44670
    Mexico

    Site Not Available

  • Research Site

    Monterrey, 64060
    Mexico

    Site Not Available

  • Research Site

    Veracruz, 91910
    Mexico

    Site Not Available

  • Research Site

    Badalona(Barcelona), 08916
    Spain

    Active - Recruiting

  • Research Site

    Barcelona, 08035
    Spain

    Active - Recruiting

  • Research Site

    Lugo, 27002
    Spain

    Active - Recruiting

  • Research Site

    Madrid, 28041
    Spain

    Active - Recruiting

  • Research Site

    Pamplona, 31008
    Spain

    Active - Recruiting

  • Research Site

    Rosario, 2002
    Spain

    Active - Recruiting

  • Research Site

    Belfast, BT9 7BL
    United Kingdom

    Site Not Available

  • Research Site

    Liverpool, L7 8XP
    United Kingdom

    Active - Recruiting

  • Research Site

    London, SE1 9RT
    United Kingdom

    Site Not Available

  • Research Site

    Southampton, SO16 6YD
    United Kingdom

    Active - Recruiting

  • Research Site

    Palmdale, California 93551
    United States

    Active - Recruiting

  • Research Site

    Colorado Springs, Colorado 80907
    United States

    Active - Recruiting

  • Research Site

    Miami, Florida 33136
    United States

    Active - Recruiting

  • Research Site

    Hyattsville, Maryland 20782
    United States

    Active - Recruiting

  • Research Site

    Boston, Massachusetts 02115
    United States

    Active - Recruiting

  • Research Site

    Saint Louis, Missouri 63110
    United States

    Active - Recruiting

  • Research Site

    New Brunswick, New Jersey 08901
    United States

    Active - Recruiting

  • Research Site

    Oklahoma City, Oklahoma 73120
    United States

    Active - Recruiting

  • Research Site

    McAllen, Texas 78503
    United States

    Active - Recruiting

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