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.
- Conditions
- Severe Asthma
- Interventions
- Combination Product: TezepelumabCombination Product: Budesonide/formoterolCombination Product: Albuterol/budesonide (AIRSUPRA®)Combination Product: MannitolCombination Product: Salbutamol
- Registration Number
- NCT06473779
- Lead Sponsor
- AstraZeneca
- 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).
- Detailed 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 56)
* Maintenance Phase (Week 56 to Week 72)
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 300
Not provided
Medical Conditions
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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).
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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.
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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.
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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.
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History of chronic alcohol or drug abuse within 12 months prior to Visit 1.
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Tuberculosis requiring treatment within the 12 months prior to Visit 1.
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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.
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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.
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Evidence of COVID-19 within 4 weeks prior to screening or ongoing clinically significant COVID-19 sequelae.
Prior/Concomitant Therapy
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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.
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OCS-dependent patients (received chronic OCS therapy [prednisone ≥ 5 mg/day or equivalent]) for at least 3 months preceding Visit 1.
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Daily use of maintenance corticosteroids for any reason.
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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.
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Receipt of immunoglobulin or blood products within 30 days prior to Visit 1.
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Receipt of live attenuated vaccines 30 days prior to the date of Visit 1 and during the study.
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Patients that have been treated with bronchial thermoplasty in the last 12 months prior to Visit 1.
Prior/Concurrent Clinical Study Experience
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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.
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History of anaphylaxis or documented immune complex disease (Type III hypersensitivity reactions) following any biologic therapy.
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Concurrent enrolment in another clinical study involving an IMP.
Diagnostic Assessments
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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.
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Evidence of active liver disease, including jaundice or AST, ALT, or ALP > 2 times the ULN at Visit 1.
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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
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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.
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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.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1 - Asthma Control or Low Biomarkers - Step-down of ICS Tezepelumab 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 Group 1 - Asthma Control or Low Biomarkers - Step-down of ICS Salbutamol 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 Group 3 - No Asthma Control or Low Biomarkers - No Step-down of ICS Tezepelumab No Asthma Control or Low Biomarkers - No Step-down of ICS Group 2 - Asthma Control or Low Biomarkers - No Step-down of ICS Tezepelumab 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 Group 1 - Asthma Control or Low Biomarkers - Step-down of ICS Budesonide/formoterol 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 Group 1 - Asthma Control or Low Biomarkers - Step-down of ICS Albuterol/budesonide (AIRSUPRA®) 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 Group 2 - Asthma Control or Low Biomarkers - No Step-down of ICS Budesonide/formoterol 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 Group 2 - Asthma Control or Low Biomarkers - No Step-down of ICS Albuterol/budesonide (AIRSUPRA®) 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 Group 2 - Asthma Control or Low Biomarkers - No Step-down of ICS Salbutamol 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 Group 3 - No Asthma Control or Low Biomarkers - No Step-down of ICS Budesonide/formoterol No Asthma Control or Low Biomarkers - No Step-down of ICS Group 3 - No Asthma Control or Low Biomarkers - No Step-down of ICS Albuterol/budesonide (AIRSUPRA®) No Asthma Control or Low Biomarkers - No Step-down of ICS Group 1 - Asthma Control or Low Biomarkers - Step-down of ICS Mannitol 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 Group 2 - Asthma Control or Low Biomarkers - No Step-down of ICS Mannitol 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 Group 3 - No Asthma Control or Low Biomarkers - No Step-down of ICS Mannitol No Asthma Control or Low Biomarkers - No Step-down of ICS
- Primary Outcome Measures
Name Time Method Proportion of patients who reduced their SYMBICORT® daily maintenance dose without the loss of asthma control at the end of the step-down phase. Week 56 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
- Secondary Outcome Measures
Name Time Method 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 Week 72 among those in asthma control at Week 24; summarised separately for patients randomised to ICS step-down and for patients randomised to no step-down of ICS.
Proportion of patients in clinical remission at Week 72 among those with characteristics of clinical remission at Week 24 Week 72 Proportion of patients in clinical remission at Week 72 among those with characteristics of clinical remission at Week 24; summarised separately for patients randomised to ICS step-down and for patients randomised to no step-down of ICS.
Proportion of patients in asthma control Week 24 Proportion of patients in asthma control at Week24.
Proportion of patients with characteristics of clinical remission Week 24 Proportion of patients with characteristics of clinical remission at 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 56 among those in asthma control at Week 24; summarised separately for patients randomised to ICS step-down and for patients randomised to no step-down of ICS.
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 Proportion of patients in asthma control at both Week 56 and Week 72 among those in asthma control at Week 24; summarised separately for patients randomised to ICS step-down and for patients randomised to no step-down of ICS.
Proportion of patients in clinical remission at both Week 56 and Week 72 among those with characteristics of clinical remission at Week 24 Week 56 and Week 72 Proportion of patients in clinical remission at both Week 56 and Week 72 among those with characteristics of clinical remission at Week 24; summarised separately for patients randomised to ICS step-down and for patients randomised to no step-down of ICS.
Proportion of patients in clinical remission at Week 56 among those who demonstrated neither asthma control nor low biomarkers at Week 24 Week 56 Proportion of patients in clinical remission at Week 56 among those who demonstrated neither asthma control nor low biomarkers at Week 24
Proportion of patients in clinical remission at Week 72 among those who demonstrated neither asthma control nor low biomarkers at Week 24 Week 72 Proportion of patients in clinical remission at Week 72 among those who demonstrated neither asthma control nor low biomarkers at Week 24
Proportion of patients in complete remission at Week 72 among those in complete remission at Week 56 Week 72 Proportion of patients in complete remission at Week 72 among those in complete remission at Week 56; summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24.
Change from Week 24 at Week 72 in: ° Mean monthly maintenance ICS dose ° Mean monthly rescue ICS dose ° Mean monthly total ICS dose (maintenance and rescue doses) From Week 24 at Week 72 Change from Week 24 at Week 72 in:
* Mean monthly maintenance ICS dose
* Mean monthly rescue ICS dose
* Mean monthly total ICS dose (maintenance and rescue doses)AAER between Week 0 and Week 24 among all tezepelumab-treated patients Between Week 0 and Week 24 Annualised Asthma Exacerbation Rate between Week 0 and Week 24 among all tezepelumab-treated patients.
Proportion of patients in asthma control at Week 56 among those who demonstrated neither asthma control nor low biomarkers at Week 24 Week 56 Proportion of patients in asthma control at Week 56 among those who demonstrated neither asthma control nor low biomarkers at Week 24
Proportion of patients in clinical remission at Week 56 among those with characteristics of clinical remission at Week 24 Week 56 Proportion of patients in clinical remission at Week 56 among those with characteristics of clinical remission at Week 24; summarised separately for patients randomised to ICS step-down and for patients randomised to no step-down of ICS.
Proportion of patients in asthma control at Week 72 among those who demonstrated neither asthma control nor low biomarkers at Week 24 Week 72 Proportion of patients in asthma control at Week 72 among those who demonstrated neither asthma control nor low biomarkers at Week 24
Proportion of patients in complete remission at Week 56 Week 56 Proportion of patients in complete remission at Week 56; summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24.
Change from Week 24 at Week 56 in: ° Mean monthly maintenance ICS dose ° Mean monthly rescue ICS dose ° Mean monthly total ICS dose (maintenance and rescue doses) From Week 24 at Week 56 Change from Week 24 at Week 56 in:
* Mean monthly maintenance ICS dose
* Mean monthly rescue ICS dose
* Mean monthly total ICS dose (maintenance and rescue doses)Cumulative daily ICS dose (maintenance and rescue doses) between Week 24 and Week 56 Between Week 24 and Week 56 Cumulative daily ICS dose (maintenance and rescue doses) between Week 24 and Week 56 both summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24.
Cumulative daily ICS dose (maintenance and rescue doses) between Week 56 and Week 72 Between Week 56 and Week 72 Cumulative daily ICS dose (maintenance and rescue doses) between Week 56 and Week 72 both summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24.
Cumulative daily ICS dose (maintenance and rescue doses) between Week 24 and Week 72 Between Week 24 and Week 72 Cumulative daily ICS dose (maintenance and rescue doses) between Week 24 and Week 72 both summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24.
AAER between Week 24 and Week 56 Between Week 24 and Week 56 Annualised Asthma Exacerbation Rate between Week 24 and Week 56 summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24.
Proportion of SGRQ responders (improvement of≥ 4 in SGRQ total score) from baseline at Week 24 among all tezepelumab-treated patients. From baseline at Week 24 Proportion of SGRQ responders (improvement of≥ 4 in SGRQ total score) from baseline at Week 24 among all tezepelumab-treated patients
Proportion of SGRQ responders (improvement of≥ 4 in SGRQ total score) from Week 24 at Week 72 From Week 24 at Week 72 Proportion of SGRQ responders (improvement of≥ 4 in SGRQ total score) from Week 24 at Week 72; summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24.
Pre-BD FEV1 actual values and changes from baseline at Week 24 among all tezepelumab-treated patients. Baseline at Week 24 Asthma exacerbations, patient-reported outcomes, and lung function. Pre-BD FEV1 actual values and changes from baseline at Week 24 among all tezepelumab-treated patients.
AAER between Week 56 and Week 72 Between Week 56 and Week 72 Annualised Asthma Exacerbation Rate between Week 56 and Week 72 summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24.
ACQ-5 score and changes from Week 24 at Week 56 From Week 24 at Week 56 ACQ-5 score and changes from Week 24 at Week 56; summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24.
SGRQ total score and changes from baseline at Week 24 among all tezepelumab-treated patients. From baseline at Week 24 SGRQ total score and changes from baseline at Week 24 among all tezepelumab-treated patients.
SGRQ total score and changes from Week 24 at Week 72 From Week 24 at Week 72 SGRQ total score and changes from Week 24 at Week 72, summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24.
Pre-BD FEV1 total score and changes from Week 24 at Week 72 From Week 24 at Week 72 Pre-BD FEV1 total score and changes from Week 24 at Week 72, summarized separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24 among all tezepelumab-treated patients.
Proportion of pre-BD FEV1 responders at Week 72 among those who were pre-BDFEV1 responders at Week 24 Week 72 . Proportion of pre-BD FEV1 responders at Week 72 among those who were pre-BDFEV1 responders at Week 24; summarized separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24.
AAER between Week 24 and Week 72 Between Week 24 and Week 72 Annualised Asthma Exacerbation Rate between Week 24 and Week 72 summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24.
ACQ-5 score and changes from baseline at Week 24 among all tezepelumab-treated patients From baseline at Week 24 ACQ-5 score and changes from baseline at Week 24 among all tezepelumab-treated patients
ACQ-5 score and changes from Week 24 at Week 72 From Week 24 at Week 72 ACQ-5 score and changes from Week 24 at Week 72; summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24.
Proportion of ACQ-5 responders (improvement of≥ 0.5 in ACQ-5 score) from baseline at Week 24 among all tezepelumab-treated patients. From baseline at Week 24 Proportion of ACQ-5 responders (improvement of≥ 0.5 in ACQ-5 score) from baseline at Week 24 among all tezepelumab-treated patients.
Proportion of ACQ-5 responders (improvement of≥ 0.5 in ACQ-5 score) from Week 24 at Week 56 From Week 24 at Week 56 Proportion of ACQ-5 responders (improvement of≥ 0.5 in ACQ-5 score) from Week 24 at Week 56; summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24.
Proportion of ACQ-5 responders (improvement of≥ 0.5 in ACQ-5 score) from Week 24 at Week 72 From Week 24 at Week 72 Proportion of ACQ-5 responders (improvement of≥ 0.5 in ACQ-5 score) from Week 24 at Week 72; summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24.
SGRQ total score and changes from Week 24 at Week 56 From Week 24 at Week 56 SGRQ total score and changes from Week 24 at Week 56, summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24.
Proportion of SGRQ responders (improvement of≥ 4 in SGRQ total score) from Week 24 at Week 56 From Week 24 at Week 56 Proportion of SGRQ responders (improvement of≥ 4 in SGRQ total score) from Week 24 at Week 56; summarised separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24.
Pre-BD FEV1 total score and changes from Week 24 at Week 56 From Week 24 at Week 56 Pre-BD FEV1 total score and changes from Week 24 at Week 56, summarized separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24 among all tezepelumab-treated patients.
Proportion of pre-BD FEV1 responders from baseline at Week 24 Week 24 Proportion of pre-BD FEV1 responders from baseline (defined as patients who achieve either a≥ 5% or ≥ 100 mL improvement from baseline) at Week 24, for all tezepelumab-treated patients
Proportion of pre-BD FEV1 responders at Week 56 among those who were pre-BDFEV1 responders at Week 24 Week 56 Proportion of pre-BD FEV1 responders at Week 56 among those who were pre-BDFEV1 responders at Week 24; summarized separately for patients randomised to ICS step-down, randomised to no ICS step-down, and those who demonstrated neither asthma control nor low biomarkers at Week 24.
Trial Locations
- Locations (1)
Research Site
🇬🇧Southampton, United Kingdom