2023-504648-33-00已完成3 期
A Randomised, Double-Blind, Parallel-Group, Placebo-Controlled 28-week Phase III Efficacy and Safety Study of Tezepelumab in Reducing Oral Corticosteroid Use in Adults with Oral Corticosteroid Dependent Asthma (SUNRISE)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 76
- 试验地点
- 14
- 主要终点
- Categorised percent reduction from baseline in the daily maintenance OCS dose at Week 28 whilst maintaining asthma control. The categories for percent change from baseline in daily OCS dose are defined as: 1. ≥ 90% to ≤ 100% reduction 2. ≥ 75% to < 90% reduction 3. ≥ 50% to < 75% reduction 4. > 0% to < 50% reduction 5. no change or any increase.
研究概览
简要总结
To evaluate the effect of tezepelumab compared with placebo in reducing the prescribed OCS maintenance dose in participants with asthma requiring chronic treatment with maintenance OCS in addition to high dose ICS plus LABA
研究设计
- 分配方式
- Randomized
- 主要目的
- Enrolment/ Run-in
- 盲法
- Double (Analyst, Investigator, Subject, Monitor)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Age- Participant must be 18 to 80 years of age inclusive, at the time of signing the informed consent form
- •Participants must have a history of at least one asthma exacerbation event within 24 months prior to Visit 1
- •Body weight ≥ 40 kg at Visit 1
- •Sex: male or female
- •All women of childbearing potential must have a negative serum pregnancy test results at Visit 1 and a negative urine pregnancy test at randomisation.
- •Female participants of childbearing potential who are sexually active with a non-sterilised male partner must agree to use one highly effective method of birth control , from enrolment throughout the study and until at least 16 weeks after last dose of study intervention.
- •Capable of giving signed informed consent
- •Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports Genomic Initiative.
- •Minimum 10 days compliance with both the morning and evening daily diary completion and morning PEF measurements during the 14 days prior to Visit 2
- •Minimum 10 days compliance with OCS, ICS, LABA and other asthma controller medications as captured in the daily diary during the 14 days prior to Visit
- •Participant must have received the optimised OCS dose for at least 2 weeks prior to randomisation.
- •Documented physician-diagnosed asthma for at least 12 months prior to Visit
- •Minimum 70% compliance with all asthma controller medication dosing including OCS, ICS/LABA at Visits 3-5 during the OCS optimisation phase.
- •Minimum 70% compliance with the morning and evening daily diary completion and morning PEF measurements at Visits 3-5 during the OCS optimisation phase.
- •. Minimum 10 days compliance with the morning and evening daily diary completion and morning PEF measurement during the 14 days prior to randomisation.
- •Minimum 10 days compliance with OCS, ICS, LABA and other asthma controller medications as captured in the daily diary during the 14 days prior to randomisation.
- •Acceptable inhaler, peak flow meter, and spirometry techniques as judged by the investigator.
- •Participants must have received a physician-prescribed medium- or high-dose ICS for at least 12 months prior to Visit
- •Participants must have received physician prescribed LABA and high dose ICS for at least 3 months prior to Visit
- •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 ie, leukotriene receptor antagonists (LTRAs), theophylline, long-acting muscarinic antagonists (LAMAs), and chromones. The use of these medications must be documented for at least 3 months prior to Visit
- •Participants must have received OCS for the treatment of asthma for at least 6 months prior to Visit 1 and on a stable dose of between ≥ 7.5 to ≤ 30 mg (prednisone or prednisolone) daily or daily equivalent for at least one month prior to Visit
- •Morning pre-BD FEV1 must be < 80% predicted normal at Visit 1 or Visit
- •Evidence of asthma as documented by either: -Post-BD (albuterol/salbutamol) responsiveness test result: FEV1 ≥ 12% and ≥ 200 mL (15-30 min after administration of 4 puffs of albuterol/salbutamol), documented either in the previous 60 months prior to or at Visit 1 or at Visit 2 or at Visit
- •Airway hyperresponsiveness (methacholine: provocative concentration that causes a positive reaction [PC20] of < 8 mg/mL) documented in the 60 months prior to Visit 1
- •Blood eosinophils at Visit 1 ≥150 cells/μL(≥0.15 x109/L or ≥0.15 x103/µl) or documented EOS ≥ 300 cells/μL (≥0.3 x109 /L or ≥0.3 x103/µl) within 12 months prior to Visit 1
排除标准
- •Any clinically important pulmonary disease other than asthma (eg, active lung infection, Chronic Obstructive Pulmonary Disease (COPD), bronchiectasis, pulmonary fibrosis)
- •Receipt of live attenuated vaccines 30 days prior to the date of randomisation and during the study including the follow-up period.
- •COVID-19 vaccination within 28 days prior to randomisation.
- •Chronic alcohol or drug abuse within 12 months prior to Visit
- •Participants who have been treated with bronchial thermoplasty within 36 months prior to Visit
- •Sensitivity to any component of the study intervention formulation or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.
- •History of anaphylaxis or documented immune complex disease (Type III hypersensitivity reactions) following any biologic therapy.
- •Concurrent enrolment in another IP-related interventional clinical trial
- •Participant randomised in other ongoing or previous tezepelumab studies.
- •Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff and/or site staff), or participants employed by or relatives of the employees of the site or sponsor.
- •Any clinically meaningful abnormal findings in physical examination, vital signs, electrocardiogram (ECG), haematology, clinical chemistry, or urinalysis during the run-in period, which in the opinion of the investigator, may put the participant at risk because of his/her participation in the study, or may influence the results of the study, or the participant's ability to complete entire duration of the study
- •History of cancer
- •Tuberculosis requiring treatment within the 12 months prior to Visit
- •A positive human immunodeficiency virus (HIV) test at Visit 1 or participant taking antiretroviral medications or history of any known immunodeficiency disorder, as determined by medical history and/or participant's verbal report.
- •Major surgery within 8 weeks prior to Visit 1 or planned surgical procedures requiring general anaesthesia or hospitalisation for > 1 day during the conduct of the study.
- •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 non-biologic agent within 30 days or 5 half-lives (whichever is longer) prior to Visit
- •Treatment with the following medications within the last 12 weeks or 5 half-lives (whichever is longer) prior to Visit 1: systemic immunosuppressive/immunomodulating drugs (eg, methotrexate, cyclosporine, oral/parenteral/intra-articular corticosteroids for other use than treatment of asthma)
- •Receipt of immunoglobulin or blood products within 30 days prior to Visit
- •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: (a) Affect the safety of the participant throughout the study (b) Influence the findings of the study or the interpretation (c) Impede the participant's ability to complete the entire duration of study
- •Evidence of active liver disease, including jaundice or aspartate transaminase, alanine transaminase, or alkaline phosphatase beyond twice the upper limit of normal (ULN), at Visit
- •Positive hepatitis B surface antigen, or hepatitis C virus antibody serology at Visit 1, or a positive medical history for hepatitis B or C. Participants with a history of hepatitis B vaccination without a history of hepatitis B are allowed to participate.
- •Women who are currently pregnant (confirmed with positive pregnancy test) or breastfeeding or lactating.
- •Asthma exacerbation, requiring use of systemic corticosteroids or increase in the maintenance dose of OCS finalised within 30 days prior to Visit
- •Unwillingness or inability to follow the study procedures, or restrictions, in the opinion of the investigator.
- •Previous allogeneic bone marrow transplant.
- •Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection.
- •During the optimisation period, asthma control reached at an OCS dose of < 7.5 mg or > 30 mg and/or 3 consecutive dose reductions after which asthma control was still obtained.
- •Evidence of clinically significant infection (including COVID-19) or participant receiving treatment with systemic antibiotics or antiviral medications.
- •Despite screening of the participant, enrolment/randomisation is stopped at the study level.
- •Clinically significant infection, including upper or lower respiratory tract infection (URTI and LRTI, respectively), requiring treatment with systemic antibiotics or antiviral medications finalised < 2 weeks before Visit 1 or during the run-in period.
- •Participants with evidence of active COVID-19 infection during run-in period and optimisation. Evaluation will be based on local standard of care as determined by current local guidelines.
- •A helminth 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.
- •A participant who is on short-acting beta agonists (SABA) maintenance treatment within 30 days prior to Visit
- •Current smokers or participants with smoking history ≥ 10 pack-years and participants 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.
- •Receipt of the T2 cytokine inhibitor Suplatast tosilate within 15 days prior to Visit 1.
结局指标
主要结局
Categorised percent reduction from baseline in the daily maintenance OCS dose at Week 28 whilst maintaining asthma control. The categories for percent change from baseline in daily OCS dose are defined as: 1. ≥ 90% to ≤ 100% reduction 2. ≥ 75% to < 90% reduction 3. ≥ 50% to < 75% reduction 4. > 0% to < 50% reduction 5. no change or any increase.
Categorised percent reduction from baseline in the daily maintenance OCS dose at Week 28 whilst maintaining asthma control. The categories for percent change from baseline in daily OCS dose are defined as: 1. ≥ 90% to ≤ 100% reduction 2. ≥ 75% to < 90% reduction 3. ≥ 50% to < 75% reduction 4. > 0% to < 50% reduction 5. no change or any increase.
次要结局
- 1. Change from baseline in pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV1) at Week 28.
- 2. Proportion of participants with 100% reduction from baseline in daily maintenance OCS dose at Week 28
- 3. Proportion of participants with daily maintenance OCS dose ≤ 5 mg at Week 28
- 4. Proportion of participants with ≥ 50% reduction from baseline in daily maintenance OCS dose at Week 28
- 5. Annualised asthma exacerbation rate (AAER) over 28 weeks
- 6. Time to first asthma exacerbation
- 7. Change from baseline in • Asthma Control Questionnaire 6 (ACQ-6) score at Week 28 • Weekly mean home peak expiratory flow (PEF) (morning and evening) at Week 28
- 8. Change from baseline in: • Standardized Asthma Quality of Life Questionnaire for 12 years and older (AQLQ(s)+12) total score at Week 28 • St George's Respiratory Questionnaire (SGRQ) score at Week 28
- 9. Change from baseline in fractional exhaled nitric oxide (FeNO), peripheral blood eosinophils and total serum immunoglobulin E (IgE) at Week 28
- 10.Tezepelumab serum trough concentrations at Week 0, 12, and 28
- 11.Incidence of anti-drug antibodies (ADAs) at Week 0, 12, 28, and 40
研究者
AstraZeneca Clinical Study Information Center
Scientific
AstraZeneca AB
研究点 (14)
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