Phase 3b Study in Patients With Severe Asthma Treated With TezepelumabTAPER

1．Provision of informed consent prior to any study-specific procedures. Written informed consent, and assent when applicable for study participation must be obtained prior to any study related procedures being performed (local regulations are to be followed in determining the assent/consent requirements for children and parent\[s\]/guardian\[s\]) and according to international guidelines and/or applicable local guidelines. Age 2. Patient must be aged 12-80 years old, inclusively, at the time of Visit 1(Week -1 to Week 0) For those patients, who are 17 on the day of Visit 1(Week -1 to Week 0) but will turn 18 after this day, will be considered an adolescent for the purposes of this study. Type of Patient and Disease Characteristics 3. Documented history of physician-diagnosed asthma prior to Visit 1 * Documented post-bronchodilator (post-BD) reversibility in FEV1 of ≥12% and ≥200 mL in FEV1, or FEV1≥400 mL variability over time, or positive result of branchial provocation test within 12 months prior to Visit 1. If historical documentation is not available, reversibility must be demonstrated and documented at Visit 1. 4\. Documented current maintenance treatment with MD/HD ICS + LABA with up to one additional controller * Other acceptable asthma controller includes LTRA, LAMA or theophylline 5. On stable MD/HD ICS (\>250μg fluticasone propionate dry powder formulation equivalents total daily dose) + LABA stable for ≥2 months prior to enrollment 6. On stable LTRA or LAMA or theophylline (≥2 weeks) is allowed 7. Documented ACQ-5 ≥ 1.5 in Visit 1 8. Documented at least one exacerbation in the year prior to enrolment * A qualifying historical asthma exacerbation is a symptomatic worsening requiring systemic corticosteroid (i.e., oral, intravenous (IV) or intramuscular; any healthcare setting or temporary increase from a stable maintenance dose of oral corticosteroid) or that resulted in hospitalization or emergency room/urgent care visit. * Source documentation is required for physician-diagnosed asthma, ICS-LABA use and asthma exacerbations over the prior year. A patient verbal history suggestive of asthma symptoms and/or prior asthma exacerbations, but without supporting documentation, is not sufficient to satisfy these inclusion criteria. * Examples of acceptable documentation of the asthma disease state and prior asthma exacerbations include clinic visit (primary or specialist Health care provider (HCP)), emergency room/urgent care, or hospital records listing asthma as a current problem, plus documentation of at least 1 asthma exacerbations during the 12 months prior to ICF. Weight 9. Weight of ≥40 kg at Visit 1. Sex and Contraceptive/Barrier Requirements 10. Male and/or female Contraceptive use by females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Female patients: * Females not of childbearing potential are defined as females who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Females will be considered postmenopausal if they have been amenorrhoeic for 12 months prior to Visit 1(Week -1 to Week 0) without an alternative medical cause. The following age-specific requirements apply: * Females \< 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and FSH levels in the postmenopausal range. * Females ≥ 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment. * Female patients of childbearing potential must use one highly effective form of birth control. A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly. Females of childbearing potential who are sexually active with a non-sterilised male partner must agree to use one highly effective method of birth control, as defined below, from enrolment throughout the study and until at least 8 weeks after last dose of study intervention. Cessation of contraception after this point should be discussed with a responsible physician. * The following are not acceptable methods of contraception: periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea. Female condom and male condom should not be used together. * All WOCBP must have a negative serum pregnancy test result at Visit 1(Week -1 to Week 0). * Highly effective birth control methods include: Total sexual abstinence is an acceptable method provided it is the usual lifestyle of the patient (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments) \[(periodic abstinence eg, calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to study intervention, and withdrawal are not acceptable methods of contraception\], a vasectomised partner, Implanon®, bilateral tubal occlusion, intrauterine device/levonorgestrel intrauterine system, Depo-Provera™ injections, oral contraceptive, and Evra Patch™, Xulane™, or NuvaRing®.

Medical Conditions 1. Unable to commit to the scheduled visits as required by the protocol, or unable to commit to undergoing protocol guided reductions in asthma therapy, as directed by the Investigator. 2. Clinically important pulmonary disease other than asthma (e.g., active lung infection, chronic obstructive pulmonary disease \[COPD\], bronchiectasis, pulmonary fibrosis, cystic fibrosis), or ever been diagnosed with pulmonary or systemic disease, other than asthma, that is associated with elevated peripheral eosinophil counts (e.g., allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome, hypereosinophilic syndrome). • Within the 12 months prior to Visit 1, a CT scan is required to exclude related diseases. 3. Current smokers at Visit 1 are not allowed. Former smokers with smoking history ≥ 10 pack-years at Visit 1 are not allowed; Former smokers with a smoking history of \<10 pack years must have stopped for at least 6 months to be eligible. 4. History of alcohol or drug abuse within 12 months prior to Visit 1(Week -1 to Week 0). 5. A helminth parasitic infection diagnosed within 24 weeks prior to Visit 1(Week -1 to Week 0) that has not been treated with, or has failed to respond to, standard of care therapy. 6. History of anaphylaxis to any biologic therapy. 7. Known history of allergy or reaction to any component of the study treatment formulation. 8. Respiratory exacerbation requiring use of Systemic corticosteroids (SCS) or acute upper/lower respiratory infection that required antibiotics or antiviral medication within 30 days prior to Visit 1(Week -1 to Week 0). An extension of the screening period up to 3 months is allowed to ensure that a patient recovering from any repiratory exacerbation or acute upper/lower respiratory infection can be included. 9. A history of known immunodeficiency disorder, including human immunodeficiency virus. 10. Current or history of malignancy within 5 years before the screening visit with the following exceptions: * In-situ carcinoma of the cervix where curative therapy has been completed and patients are in remission for at least 12 months prior to screening. * Basal cell or superficial squamous skin cancer. * Patients who have had other malignancies are eligible provided that the patient is in remission and curative therapy was completed at least 5 years prior to the date informed consent was obtained. 11. Exclusion for any of the following: * Previous allogeneic bone marrow transplant. * Non-leucocyte depleted whole blood transfusion within 120 days of genetic sample collection. 12. 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: 1. Affect the safety of the patient throughout the study, 2. Confound the study results or impact the scientific validity of the data outcome, 3. Impede the patient's ability to complete the entire duration of study. Prior/Concomitant Therapy 13. Oral corticosteroid use during 4 weeks prior to Visit 1(Week -1 to Week 0). 14. Use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroid, or any experimental anti-inflammatory therapy) within 3 months or 5 halflives (whichever is longer) prior to the date informed consent is obtained. 15. Receipt of any marketed or investigational biologic agent within 4 months or 5 half lives (whichever is longer) prior to Visit 1(Week -1 to Week 0) or receipt of any investigational non biologic agent within 30 days or 5 half-lives (whichever is longest) prior to Visit 1(Week -1 to Week 0). Exception: 1. For marketed non-respiratory biologics, it is allowed if the patient is stable on treatment for at least 3 months prior to Visit 1(Week -1 to Week 0) and throughout the study. 2. Covid-related prevention and treatment 16. Receipt of live attenuated vaccines 30 days prior to the date of first dose of Tezepelumab. 17. Intention to use any concomitant medication that is not permitted or failure to complete the required washout period for a particular prohibited medication. 18. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained. 19. Received bronchial thermoplasty (BT) as treatment of asthma within 12 months prior to Visit 1. 20. Received treatment with traditional Chinese herbs or proprietary Chinese medicines that have anti-asthmatic effects (excluding topical Chinese herbs) within 4 weeks prior to Visit 1 (Week -1 to Week 0) Prior/Concurrent Clinical Study Experience 21. Concurrent participation in another clinical study with an Investigational Product or a post-authorization safety study Diagnostic Assessments 22. Any clinically significant abnormal findings in physical examination, medical history, vital signs, haematology, or clinical chemistry during the enrolment period, 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, e.g. HBV, HCV, active liver disease, Receipt of live attenuated vaccines 30 days prior to the date of visit 1. Other Exclusions 23. For females only - currently pregnant (confirmed with positive pregnancy test), breast-feeding, or lactating. 24. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). 25. 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. 26. Previous enrolment in the present study.