TEZEPELUMAB for Severe asthma | Asthma

Inclusion criteria

• {"criterion_text":"-Minimum age: 18\n-Based on results of screening visit and run-in: Oral corticosteroid maintenance therapy (if used) is 7.5 mg/day\n-Based on results of screening visit and run-in: On CT scan, the average percentage wall area index at the B1 and B8 bronchi (generation 3, 4, 5) is >65%\n-Maximum age: 85\n-Able to perform an inspiratory and expiratory thoracic computed tomography (CT) scan, plus a nasal CT\n-In stable condition for CT scan\n-Physician-diagnosed asthma according to GINA criteria\n-Disease with clinical impact: at least 1 severe or 2 moderate exacerbations in the previous 12 months despite treatment according to the best standards of care\n-Maximal inhaled therapy comprising high dose ICS and at least a second controller according to GINA\n-Based on results of screening visit and run-in: Post-bronchodilator forced expiratory volume in 1 second (FEV1) predicted values must be at 25-90%\n-Based on results of screening visit and run-in: Asthma Control Questionnaire 6 (ACQ6) > 1.5"}

Exclusion criteria

• {"criterion_text":"-CT abnormalities evocative of any respiratory condition other than asthma\n-Potential interference from other studies\n-Protected populations according to the French public health code\n-Male or female patients seeking to conceive a child\n-Women of childbearing potential and fertile men not using birth control method\n-Pregnant, breastfeeding or lactating women\n-History of a clinically significant infection, including upper (URTI) or lower respiratory tract infection (LRTI), requiring treatment with antibiotics or antiviral medications finalised < 2 weeks before randomization. Patients with pre-existing serious infections should be treated before initiating therapy with tezepelumab\n-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\n-Patients using vaping products, including electronic cigarettes (because may induce abnormality at CT scan)\n-Bronchial thermoplasty in the last 12 months prior to Visit 1\n-History of documented immune complex disease (Type III hypersensitivity reactions) following any biologic therapy\n-Treatment regimen discordant with best practices\n-History of known immunodeficiency disorder including a positive human immunodeficiency virus test or the participant taking antiretroviral medications as determined by medical history and/or participant’s verbal report\n-Receipt of the T2 cytokine inhibitor Suplatast tosilate within 15 days prior to randomization\n-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 randomization\n-Receipt of immunoglobulin or blood products within 30 days prior to randomization\n-Receipt of allergen immunotherapy not stable within 30 days prior to randomization or with anticipated change during the treatment period\n-Pulmonary disease other than asthma‡ requiring treatment during the previous 12 months\n-A smoking history of >20 pack years\n-Receipt of any marketed or investigational biologic agent within 3 months or 5 half-lives (whichever is longer) prior to randomization or receipt of any investigational non biologic agent within 30 days or 5 half-lives (whichever is longest) prior to randomization or receipt of live attenuated vaccines 30 days prior to the date of randomization. Participants enrolled in current or previous tezepelumab studies will not be included. Participants on previous biologics treatment are allowed to enter the study provided the appropriate washout period is fulfilled.\n-Absence of signed consent\n-Non-beneficiary of the French social security, single-payer health insurance system\n-Presence of any condition (physical, psychological or other) that might, in the investigator’s opinion, hinder study performance\n-The patient is unavailable or unwilling to participate in future visits"}

Primary endpoints

• {"endpoint_text":"-Comparaison on CT-scan in the change in mean percentage bronchial wall area (%WA) at the B1 and B8 bronchi, generations 3, 4 and 5 between baseline and 6 months","definition_or_measurement_approach":"Mean percentage bronchial wall area (%WA) measured on CT scan at bronchi B1 and B8 (generations 3-5). %WA = (wall area (mm2) / (wall area (mm2) + lumen area (mm2))) × 100; comparison of change from baseline to 6 months between treatment arms."}

Secondary endpoints

• {"endpoint_text":"-Comparaison on CT-scan the change in mean %WA between arms between baseline and 12 months","definition_or_measurement_approach":"Measured by CT scan; comparison of change in mean %WA between arms from baseline to 12 months."}
• {"endpoint_text":"-Comparaison on CT-scan in the average percentage bronchia wall thickness index (%WT) at the B1 and B8 bronchi, generations 3, 4 and 5 between baseline and 6 months","definition_or_measurement_approach":"Measured by CT scan; change in average %WT at bronchi B1 and B8 (generations 3-5) from baseline to 6 months."}
• {"endpoint_text":"-Comparaison on CT-scan in the average percentage bronchia wall thickness index (%WT) at the B1 and B8 bronchi, generations 3, 4 and 5 between baseline and 12 months","definition_or_measurement_approach":"Measured by CT scan; change in average %WT at bronchi B1 and B8 from baseline to 12 months."}
• {"endpoint_text":"-Comparaison on CT-scan the change in wall area at the B1 and B8 bronchi, generations 3, 4 and 5 between baseline and 6 months","definition_or_measurement_approach":"Measured by CT scan; change in wall area (mm2) at bronchi B1 and B8 from baseline to 6 months."}
• {"endpoint_text":"-Comparaison on CT-scan the change in lumen area at the B1 and B8 bronchi, generations 3, 4 and 5 between baseline and 6 months","definition_or_measurement_approach":"Measured by CT scan; change in lumen area (mm2) at bronchi B1 and B8 from baseline to 6 months."}
• {"endpoint_text":"-Comparaison on CT-scan the change in ratio wall area (WA) / lumen area(LM) at the B1 and B8 bronchi, generations 3, 4 and 5 between baseline and 6 months","definition_or_measurement_approach":"Measured by CT scan; change in WA/LM ratio at bronchi B1 and B8 from baseline to 6 months."}
• {"endpoint_text":"-Comparaison on CT-scan the change in lumen diameter at the B1 and B8 bronchi, generations 3, 4 and 5 between baseline and 6 months","definition_or_measurement_approach":"Measured by CT scan; change in lumen diameter at bronchi B1 and B8 from baseline to 6 months."}
• {"endpoint_text":"-Comparaison on CT-scan the change in lumen circularity at the B1 and B8 bronchi, generations 3, 4 and 5 between baseline and 6 months","definition_or_measurement_approach":"Measured by CT scan; change in lumen circularity at bronchi B1 and B8 from baseline to 6 months."}
• {"endpoint_text":"-Comparaison on CT-scan in the average percentage bronchial wall area(%WA) corrected by body surface area(BSA) at the B1 and B8 bronchi, generations 3, 4 and 5 between baseline and 6 months","definition_or_measurement_approach":"Measured by CT scan and corrected by BSA; change in %WA at bronchi B1 and B8 from baseline to 6 months."}
• {"endpoint_text":"-Comparaison on CT-scan in the average percentage bronchial wall thickness (%WT) corrected by body surface area (BSA) at the B1 and B8 bronchi, generations 3, 4 and 5 between baseline and 6 months","definition_or_measurement_approach":"Measured by CT scan and corrected by BSA; change in %WT at bronchi B1 and B8 from baseline to 6 months."}
• {"endpoint_text":"-Change in the expiratory to inspiration ratio of mean lung density (MLDe/i) at Baseline, 6 months and 12 months","definition_or_measurement_approach":"Measured by CT scan; ratio of mean lung density expiratory to inspiratory at baseline, 6 and 12 months."}
• {"endpoint_text":"-Quantitative computed tomography measurements to evaluate airflow obstruction at Baseline, 6 months and 12 months","definition_or_measurement_approach":"Quantitative CT measurements assessing airflow obstruction at baseline, 6 and 12 months."}
• {"endpoint_text":"-Change in Total small Airway Count (TAC) between Baseline and 6 months","definition_or_measurement_approach":"Change in Total small Airway Count measured by CT between baseline and 6 months."}
• {"endpoint_text":"-Change in Total small Airway Count (TAC) between Baseline and 12 months","definition_or_measurement_approach":"Change in TAC measured by CT between baseline and 12 months."}
• {"endpoint_text":"-Change in Lund Mackay score between Baseline and 6 months","definition_or_measurement_approach":"Change in Lund Mackay score (sinonasal CT score) between baseline and 6 months."}
• {"endpoint_text":"-Change in Lund Mackay score between Baseline and 12 months","definition_or_measurement_approach":"Change in Lund Mackay score between baseline and 12 months."}
• {"endpoint_text":"-Change in Presence/absence of nasal polyposis between Baseline and 6 months","definition_or_measurement_approach":"Assessment of presence/absence of nasal polyposis between baseline and 6 months (clinical/CT assessment)."}
• {"endpoint_text":"-Change in Presence/absence of nasal polyposis between Baseline and 12 months","definition_or_measurement_approach":"Assessment of presence/absence of nasal polyposis between baseline and 12 months."}
• {"endpoint_text":"-Change in Annualized exacerbation rates between Baseline and 12 months","definition_or_measurement_approach":"Change in annualized exacerbation rate comparing baseline and 12 months (clinical event rate)."}
• {"endpoint_text":"-Change in Days alive and not exacerbating between Baseline and 12 months","definition_or_measurement_approach":"Change in number of days alive and without exacerbation between baseline and 12 months."}
• {"endpoint_text":"-Change in Days alive and not hospitalized between Baseline and 12 months","definition_or_measurement_approach":"Change in number of days alive and not hospitalized between baseline and 12 months."}
• {"endpoint_text":"-Change in forced expiratory volume in 1 second between Baseline and 6 months","definition_or_measurement_approach":"Change in FEV1 (L or % predicted) between baseline and 6 months measured by spirometry."}
• {"endpoint_text":"-Change in forced expiratory volume in 1 second between Baseline and 12 months","definition_or_measurement_approach":"Change in FEV1 between baseline and 12 months measured by spirometry."}
• {"endpoint_text":"-Change in forced vital capacity between Baseline and 6 months","definition_or_measurement_approach":"Change in FVC between baseline and 6 months measured by spirometry."}
• {"endpoint_text":"-Change in forced vital capacity between Baseline and 12 months","definition_or_measurement_approach":"Change in FVC between baseline and 12 months."}
• {"endpoint_text":"-Change in forced expiratory volume in 1 second / forced vital capacity Ratio between Baseline and 6 months","definition_or_measurement_approach":"Change in FEV1/FVC ratio between baseline and 6 months."}
• {"endpoint_text":"-Change in forced expiratory volume in 1 second / forced vital capacity Ratio between Baseline and 12 months","definition_or_measurement_approach":"Change in FEV1/FVC ratio between baseline and 12 months."}
• {"endpoint_text":"-Change in total lung capacity between Baseline and 6 months","definition_or_measurement_approach":"Change in total lung capacity (TLC) between baseline and 6 months (measured by pulmonary function testing)."}
• {"endpoint_text":"-Change in total lung capacity between Baseline and 12 months","definition_or_measurement_approach":"Change in TLC between baseline and 12 months."}
• {"endpoint_text":"-Change in residual volume between Baseline and 6 months","definition_or_measurement_approach":"Change in residual volume (RV) between baseline and 6 months."}
• {"endpoint_text":"-Change in residual volume between Baseline and 12 months","definition_or_measurement_approach":"Change in residual volume between baseline and 12 months."}
• {"endpoint_text":"-Change in total lung capacity (TLC)/ residual volume(RV) ratio between Baseline and 6 months","definition_or_measurement_approach":"Change in TLC/RV ratio between baseline and 6 months."}
• {"endpoint_text":"-Change in total lung capacity (TLC)/ residual volume(RV) ratio between Baseline and 12 months","definition_or_measurement_approach":"Change in TLC/RV ratio between baseline and 12 months."}
• {"endpoint_text":"-Change in mean ACQ (Asthma Control Questionnaire)-6 score between Baseline and 6 months","definition_or_measurement_approach":"Change in mean ACQ-6 score between baseline and 6 months (patient-reported outcome)."}
• {"endpoint_text":"-Change in mean ACQ (Asthma Control Questionnaire)-6 score between Baseline and 12 months","definition_or_measurement_approach":"Change in mean ACQ-6 score between baseline and 12 months."}
• {"endpoint_text":"-Change in Breathlessness, Cough and Sputum Scale (BCSS) between Baseline and 6 months","definition_or_measurement_approach":"Change in BCSS score between baseline and 6 months (patient-reported)."}
• {"endpoint_text":"-Change in Breathlessness, Cough and Sputum Scale (BCSS) between Baseline and 12 months","definition_or_measurement_approach":"Change in BCSS score between baseline and 12 months."}
• {"endpoint_text":"-Change in Sino Nasal Outcome Test 22 between Baseline and 6 months","definition_or_measurement_approach":"Change in SNOT-22 score between baseline and 6 months (patient-reported sinonasal outcome)."}
• {"endpoint_text":"-Change in Sino Nasal Outcome Test 22 between Baseline and 12 months","definition_or_measurement_approach":"Change in SNOT-22 score between baseline and 12 months."}
• {"endpoint_text":"-Change in St George Respiratory Questionnaire (SGRQ) between Baseline and 6 months","definition_or_measurement_approach":"Change in SGRQ score between baseline and 6 months (health-related quality of life)."}
• {"endpoint_text":"-Change in St George Respiratory Questionnaire (SGRQ) between Baseline and 12 months","definition_or_measurement_approach":"Change in SGRQ score between baseline and 12 months."}
• {"endpoint_text":"-Change in ECRHS III Main Questionnaire between Baseline and 6 months","definition_or_measurement_approach":"Change in ECRHS III main questionnaire responses between baseline and 6 months."}
• {"endpoint_text":"-Change in ECRHS III Main Questionnaire between Baseline and 12 months","definition_or_measurement_approach":"Change in ECRHS III main questionnaire responses between baseline and 12 months."}
• {"endpoint_text":"-Changes in serum Club cell secretory protein (CCSP) between baseline and 6 months","definition_or_measurement_approach":"Change in serum CCSP concentrations between baseline and 6 months (laboratory measurement)."}
• {"endpoint_text":"-Changes in serum Club cell secretory protein (CCSP) between baseline and 12 months","definition_or_measurement_approach":"Change in serum CCSP concentrations between baseline and 12 months."}
• {"endpoint_text":"-Number of adverse event between arms between baseline and 6 months","definition_or_measurement_approach":"Count and comparison of adverse events between arms from baseline to 6 months (safety endpoint)."}

France

Earliest CTIS Part Ii Submission Date

24-06-2024

Latest Decision Or Authorization Date

20-02-2025

Processing Time Days

241

Number Of Sites

11

Number Of Participants

150

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Montpellier

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"AstraZeneca","duties_or_roles":"Source of monetary support","organisation_type":""}