Clinical Trials List
Protocol NumberD3250C00065
2018-09-01 - 2022-03-31
Phase III
Recruiting8
ICD-10J45.51
Severe persistent asthma with (acute) exacerbation
PONENTE: A multicenter, open-label, Phase 3b trial for adult patients with severe eosinophilic leukocyte asthma who are treated with high-dose corticosteroid inhalers, plus long-acting beta 2 agonists and oral corticosteroids for long-term treatment, to evaluate subcutaneously Efficacy and safety of 30 mg injection of Benralizumab for reducing oral corticosteroid dosage
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Trial Applicant
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Sponsor
AstraZeneca
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Taipei Medical University Hospital
Taiwan National PI
郭漢彬
Co-Principal Investigator
- Chun-Liang Chou Division of Thoracic Medicine
- Pai-Chien Chou Division of Thoracic Medicine
- Shih-Hsin Hsiao Division of Thoracic Medicine
- Chi-Li Chung Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
1 Recruiting
Audit
None
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 覃俊士 Division of Thoracic Medicine
- 王振宇 Division of Thoracic Medicine
- Wei- Chang Huang Division of Thoracic Medicine
- Ming -Cheng Chan Division of Thoracic Medicine
- 王俊隆 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Shuo-Chueh Chen Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 林孟志 Division of Thoracic Medicine
- Chia-Cheng Tseng Division of Thoracic Medicine
- 陳永哲 Division of Thoracic Medicine
- 吳沼漧 Division of Thoracic Medicine
- 趙東瀛 Division of Thoracic Medicine
- 蘇茂昌 Division of Thoracic Medicine
- CHIN-CHOU WANG Division of Thoracic Medicine
- 張晃智 Division of Thoracic Medicine
- 陳泓丞 Division of Thoracic Medicine
- 梁深怡 Division of Thoracic Medicine
- 劉世豐 Division of Thoracic Medicine
- 黃國棟 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Tzu-Tao Chen Division of Thoracic Medicine
- Chien-Hua Tseng Division of Thoracic Medicine
- Wen-Te Liu Division of Thoracic Medicine
- Po-Hao Feng Division of Thoracic Medicine
- Kuan-Yuan Chen Division of Thoracic Medicine
- YEN-HAN TSENG Division of Thoracic Medicine
- Ching-Shan Luo Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
3 Recruiting
Audit
CRO
Co-Principal Investigator
- Inn-Wen Chong 無
- 鄭孟軒 無
- 陳家閔 無
- Ming-Ju Tsai 無
- 郭家佑 無
- Jen-Yu Hung 無
- 李玫萱 無
- Ying-Ming Tsai Tsai 無
- Wei-An Chang 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 陳彥甫 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Severe eosinophilic leukocyte asthma
Objectives
For adult patients with severe eosinophilic leukocyte asthma, the effect of subcutaneous injection of 30 mg of Benralizumab on reducing oral corticosteroid (OCS) dose was evaluated.
Test Drug
Benralizumab
Active Ingredient
Humanized IL-5Rα mAb
Dosage Form
vial
Dosage
30
Endpoints
main target
Main outcome measure
- The daily OCS dose is reduced by 100%, and the asthma has not worsened for at least 4 weeks
- Daily OCS dose reduced by 100% or reduced to ≤5 mg (can not continue to reduce OCS dose due to occurrence of AI), and patients with asthma that have not worsened for at least 4 weeks
Important supporting outcome measures
- Daily OCS dose is reduced to ≤ 5 mg, for patients with asthma that has not worsened for at least 4 weeks
- Reduced average daily OCS dose by ≥90%, ≥75% and ≥50% for patients with asthma that has not worsened for at least 4 weeks
- From the beginning of the OCS dose reduction to the end of the OCS dose reduction period, the average daily OCS dose (mg) relative to the baseline change
Secondary goal
Important outcome measurement
- Daily OCS dose changes from the end of the OCS dose reduction period to the end of the maintenance period (EOT return visit)
• The time from the OCS dose reduction phase to the lowest OCS dose to the first increase in the OCS dose during the maintenance phase Important outcome measurement
- Baseline (2nd visit), 3rd visit, when the OCS dose reaches 5 mg, at the end of the OCS dose reduction period, from the end of the OCS dose reduction period to the end of the maintenance period (EOT return visit) every month ACQ-6 score
- At the third visit, when the OCS dose reaches 5 mg, the OCS dose reduction period ends, and the maintenance period ends (EOT return visit), the change in ACQ-6 score relative to the baseline
- From the second visit to the end of the maintenance period, the treatment responder analysis of ACQ-6 scores (Responder analysis)
Important outcome measurement
The change in the total score of the St. George's Respiratory Questionnaire (SGRQ) from the baseline at the end of the maintenance period (EOT return visit).
- At the end of the maintenance period, the treatment responder analysis of the SGRQ total score (Responder analysis)
Security goal
Important outcome measurement
- Patients with complete AI
Important outcome measurement
-Annual incidence of acute exacerbation of severe asthma
-The incidence of acute exacerbation of severe asthma that leads to hospitalization or emergency medical treatment each year
-Adverse Events/Serious Adverse Events
-Laboratory parameters and vital signs
-Glucocorticoid Toxicity Index
Exploratory goal
Outcome measurement
-The correlation between common and rare genetic variants and patient response to treatment
-Patient's overall impression of changes in symptoms
Important outcome measurement
-Changes in the number of eosinophils in the blood relative to the reference point
Important biomarker parameters
- Reference point serum sampling for protein biomarker analysis
- Plasma sampling for eosinophilic leukocyte neurotoxin analysis
Main outcome measure
- The daily OCS dose is reduced by 100%, and the asthma has not worsened for at least 4 weeks
- Daily OCS dose reduced by 100% or reduced to ≤5 mg (can not continue to reduce OCS dose due to occurrence of AI), and patients with asthma that have not worsened for at least 4 weeks
Important supporting outcome measures
- Daily OCS dose is reduced to ≤ 5 mg, for patients with asthma that has not worsened for at least 4 weeks
- Reduced average daily OCS dose by ≥90%, ≥75% and ≥50% for patients with asthma that has not worsened for at least 4 weeks
- From the beginning of the OCS dose reduction to the end of the OCS dose reduction period, the average daily OCS dose (mg) relative to the baseline change
Secondary goal
Important outcome measurement
- Daily OCS dose changes from the end of the OCS dose reduction period to the end of the maintenance period (EOT return visit)
• The time from the OCS dose reduction phase to the lowest OCS dose to the first increase in the OCS dose during the maintenance phase Important outcome measurement
- Baseline (2nd visit), 3rd visit, when the OCS dose reaches 5 mg, at the end of the OCS dose reduction period, from the end of the OCS dose reduction period to the end of the maintenance period (EOT return visit) every month ACQ-6 score
- At the third visit, when the OCS dose reaches 5 mg, the OCS dose reduction period ends, and the maintenance period ends (EOT return visit), the change in ACQ-6 score relative to the baseline
- From the second visit to the end of the maintenance period, the treatment responder analysis of ACQ-6 scores (Responder analysis)
Important outcome measurement
The change in the total score of the St. George's Respiratory Questionnaire (SGRQ) from the baseline at the end of the maintenance period (EOT return visit).
- At the end of the maintenance period, the treatment responder analysis of the SGRQ total score (Responder analysis)
Security goal
Important outcome measurement
- Patients with complete AI
Important outcome measurement
-Annual incidence of acute exacerbation of severe asthma
-The incidence of acute exacerbation of severe asthma that leads to hospitalization or emergency medical treatment each year
-Adverse Events/Serious Adverse Events
-Laboratory parameters and vital signs
-Glucocorticoid Toxicity Index
Exploratory goal
Outcome measurement
-The correlation between common and rare genetic variants and patient response to treatment
-Patient's overall impression of changes in symptoms
Important outcome measurement
-Changes in the number of eosinophils in the blood relative to the reference point
Important biomarker parameters
- Reference point serum sampling for protein biomarker analysis
- Plasma sampling for eosinophilic leukocyte neurotoxin analysis
Inclution Criteria
Inclusion conditions
1. Before proceeding with any test procedure, the subject's consent form must be signed.
2. Female or male aged ≥ 18 years old at the first visit (the legal adult in Taiwan is 20 years old).
3. Women with childbearing potential (WOCBP) must agree to use a highly effective contraceptive measure (confirmed by the trial host) during the period of inclusion in the test until 16 weeks after receiving the last dose of the test drug. Efficient contraceptive measures include: compound hormonal contraceptive methods related to ovulation inhibition (including estrogen and progesterone)-oral, intravaginal or transdermal, and hormonal contraceptive methods related to ovulation suppression that use only progesterone-oral, intravaginal or implant Access, intrauterine contraceptive device (IUD), intrauterine administration system (IUS), bilateral fallopian tube obstruction, abstinence, that is, avoiding sexual intercourse with the opposite sex (must be based on the patient’s clinical testing period and the patient’s preferred method of contraception and daily routine Lifestyle to assess the reliability of abstinence), the sex partner who removed the vas deferens, the partner is the only sexual partner of the fertile female (WOCBP) patient, and the partner whose vas deferens was medically evaluated as a successful operation.
Infertile women are defined as permanent sterilization (removal of the uterus, removal of both ovaries, removal of both fallopian tubes) or women who have passed through menopause. If there is no menstruation in the 12 months before the expected leading period, and there is no other medical cause, it is deemed to have stopped menstruation. The following are age-related regulations:
─Women under the age of 50 who have no menstruation for more than 12 months after stopping the exogenous hormone treatment, and the follicle stimulating hormone (FSH) concentration is within the range of menopause, it is considered as having menopause.
─A 50-year-old woman who has no menstruation for more than 12 months after stopping all exogenous hormone treatments is considered to have stopped menstruation.
4. Weight >= 40 kg.
5. Non-smokers, smokers who had smoked less than 20 packs/year at the first visit, or smokers who had smoked.
6. At the first visit, the central laboratory assessed the peripheral blood eosinophil count ≥150 cells/μL, or the medical record clearly records the eosinophil count≥300 cells/μL in the past 12 months.
7. Before the first visit, the doctor had diagnosed asthma with asthma. It is necessary to continue to receive high-dose corticosteroid inhalation (ICS) (high-dose ICS refers to the highest dose approved in China) plus long-acting β2 agonist (LABA) ) Treatment for at least 6 months. Either the compound preparation containing ICS and LABA or the use of ICS and LABA inhalants respectively:
─For ICS/LABA compound preparations, the highest locally approved maintenance dose will meet this ICS standard.
Note: Other maintenance asthma control drugs (such as leukotriene receptor antagonists (LTRA), tiotropium, cropone, theophylline) are acceptable.
8. Before the first visit, he was receiving long-term oral corticosteroid (OCS) treatment equivalent to a daily dose of at least 5 mg of prednisone, and it had lasted for at least 3 months (clearly recorded in the medical record).
Note: As long as the average daily dose is equivalent to at least 5 mg of prednisone, and is switched to daily prednisone/prednisolone at the first visit, OCS can be taken every other day (ie once every two days) or other frequency . Systemic corticosteroid therapy other than oral dosage forms cannot be considered in the average daily dose before the first visit.
9. You should receive a stable OCS dose for at least 4 weeks before the first visit. You must agree to switch your OCS treatment to prednisone/prednisolone as prescribed in the trial during the trial.
1. Before proceeding with any test procedure, the subject's consent form must be signed.
2. Female or male aged ≥ 18 years old at the first visit (the legal adult in Taiwan is 20 years old).
3. Women with childbearing potential (WOCBP) must agree to use a highly effective contraceptive measure (confirmed by the trial host) during the period of inclusion in the test until 16 weeks after receiving the last dose of the test drug. Efficient contraceptive measures include: compound hormonal contraceptive methods related to ovulation inhibition (including estrogen and progesterone)-oral, intravaginal or transdermal, and hormonal contraceptive methods related to ovulation suppression that use only progesterone-oral, intravaginal or implant Access, intrauterine contraceptive device (IUD), intrauterine administration system (IUS), bilateral fallopian tube obstruction, abstinence, that is, avoiding sexual intercourse with the opposite sex (must be based on the patient’s clinical testing period and the patient’s preferred method of contraception and daily routine Lifestyle to assess the reliability of abstinence), the sex partner who removed the vas deferens, the partner is the only sexual partner of the fertile female (WOCBP) patient, and the partner whose vas deferens was medically evaluated as a successful operation.
Infertile women are defined as permanent sterilization (removal of the uterus, removal of both ovaries, removal of both fallopian tubes) or women who have passed through menopause. If there is no menstruation in the 12 months before the expected leading period, and there is no other medical cause, it is deemed to have stopped menstruation. The following are age-related regulations:
─Women under the age of 50 who have no menstruation for more than 12 months after stopping the exogenous hormone treatment, and the follicle stimulating hormone (FSH) concentration is within the range of menopause, it is considered as having menopause.
─A 50-year-old woman who has no menstruation for more than 12 months after stopping all exogenous hormone treatments is considered to have stopped menstruation.
4. Weight >= 40 kg.
5. Non-smokers, smokers who had smoked less than 20 packs/year at the first visit, or smokers who had smoked.
6. At the first visit, the central laboratory assessed the peripheral blood eosinophil count ≥150 cells/μL, or the medical record clearly records the eosinophil count≥300 cells/μL in the past 12 months.
7. Before the first visit, the doctor had diagnosed asthma with asthma. It is necessary to continue to receive high-dose corticosteroid inhalation (ICS) (high-dose ICS refers to the highest dose approved in China) plus long-acting β2 agonist (LABA) ) Treatment for at least 6 months. Either the compound preparation containing ICS and LABA or the use of ICS and LABA inhalants respectively:
─For ICS/LABA compound preparations, the highest locally approved maintenance dose will meet this ICS standard.
Note: Other maintenance asthma control drugs (such as leukotriene receptor antagonists (LTRA), tiotropium, cropone, theophylline) are acceptable.
8. Before the first visit, he was receiving long-term oral corticosteroid (OCS) treatment equivalent to a daily dose of at least 5 mg of prednisone, and it had lasted for at least 3 months (clearly recorded in the medical record).
Note: As long as the average daily dose is equivalent to at least 5 mg of prednisone, and is switched to daily prednisone/prednisolone at the first visit, OCS can be taken every other day (ie once every two days) or other frequency . Systemic corticosteroid therapy other than oral dosage forms cannot be considered in the average daily dose before the first visit.
9. You should receive a stable OCS dose for at least 4 weeks before the first visit. You must agree to switch your OCS treatment to prednisone/prednisolone as prescribed in the trial during the trial.
Exclusion Criteria
1. Suffer from clinical major lung diseases other than asthma (such as active lung infection, chronic obstructive pulmonary disease, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome caused by obesity, lung cancer, α 1 antitrypsin & #37238; Deficiency, primary ciliary dyskinesia), or have been diagnosed with lung diseases or systemic diseases other than asthma, resulting in an increase in the number of peripheral eosinophils (such as allergic bronchial aspergillosis/mycosis, Eosinophilic granulomatous vasculitis, eosinophilic hypertrophy syndrome).
2. Known to be allergic to the test drug formulation or have had an allergic reaction.
3. Have had an allergic reaction to biological therapy.
4. The subject has been diagnosed with worm infection within 24 weeks before the day of signing the consent form, and has not been treated or has not responded to standard treatment.
5. Within 30 days before the second visit (receiving the first dose of Benralizumab), acute exacerbation of asthma occurred, requiring systemic corticosteroid therapy, increasing the maintenance dose of OCS, or having acute upper/lower respiratory tract infection. Receive antibiotic or antiviral treatment.
─The screening period can be extended up to 3 months to confirm your recovery from acute exacerbation of asthma or acute upper/lower respiratory tract infection.
6. Intend to use drugs that are forbidden in combination in this trial plan, or fail to complete the prescribed elimination period for specific prohibited drugs.
7. Has abused alcohol or drugs in the 12 months prior to the day of signing the consent form.
8. Have a history of immunodeficiency diseases, including human immunodeficiency virus (HIV) test results are positive.
9. Alanine transamine enzyme(ALT) or aspartic acid transamine enzyme (AST) concentration≥3 times the upper limit of normal (ULN) at the first visit.
10. Have received immunoglobulin or blood preparations within 30 days before the day of signing the subject's consent form.
11. At the same time participate in other clinical trials.
12. AstraZeneca employees who participated in the planning and/or execution of this trial.
13. The employees of the test institution, other personnel involved in the execution of this test, or the immediate family members of the foregoing personnel.
14. Women who are pregnant, breastfeeding or breastfeeding.
15. Have received Benralizumab treatment in this trial.
16. Simultaneously suffering from primary adrenal insufficiency (Addison's disease), or irreversible secondary adrenal insufficiency due to other independent reasons (such as pituitary gland tumor or its treatment).
17. At the same time suffering from inflammatory diseases, OCS must be used as maintenance treatment for a long time, such as (but not limited to) giant cell arteritis or rheumatic polymyalgia.
18. The exclusion conditions of genetic research include any exclusion conditions of the main experiment or any of the following conditions:
─Have had allogeneic bone marrow transplantation before.
─Have received whole blood transfusion without removing white blood cells within 120 days before the collection of genetic samples.
19. Any disease that has been judged by an experienced host to be unstable, including but not limited to cardiovascular, gastrointestinal, liver, kidney, nerve, musculoskeletal, infection, endocrine, metabolism, blood, mental or major physical damage, and may :
─Affect the safety of patients throughout the entire testing process.
─ Confuse the test results; or may affect the scientific validity of the test data results. Hinder the patient's ability to complete the entire test period.
20. According to the examination host, any clinically abnormal findings in physical examination, medical history, vital signs, hematology, clinical chemistry, or urinalysis during the recruitment period may put the patient at risk due to participation in the examination. Or it may affect the results of the test, or the patient's ability to complete the entire test period.
21. Cancer history. Patients with basal cell carcinoma, localized skin squamous cell carcinoma, or cervical carcinoma in situ can be included in the test if they are in a recovery state and have completed curative treatment at least 12 months before the date of informed consent. Patients with other malignant tumors can be included in the test if they are in a recovery state and have completed curative treatment at least 5 years before the date of obtaining informed consent.
22. During the screening period, any other (non-asthma-related) disease onset or adverse reaction/serious adverse reaction requires temporary use of systemic corticosteroids, increase in the maintenance dose of OCS, or 30 before the second visit (first use of benralizumab) Antibiotics or antiviral drugs are needed within days. However, the screening period is allowed to be extended by 3 months to ensure that the patient recovers from any non-asthma-related illness episodes or adverse reactions/serious adverse reactions.
23. Night shift staff.
2. Known to be allergic to the test drug formulation or have had an allergic reaction.
3. Have had an allergic reaction to biological therapy.
4. The subject has been diagnosed with worm infection within 24 weeks before the day of signing the consent form, and has not been treated or has not responded to standard treatment.
5. Within 30 days before the second visit (receiving the first dose of Benralizumab), acute exacerbation of asthma occurred, requiring systemic corticosteroid therapy, increasing the maintenance dose of OCS, or having acute upper/lower respiratory tract infection. Receive antibiotic or antiviral treatment.
─The screening period can be extended up to 3 months to confirm your recovery from acute exacerbation of asthma or acute upper/lower respiratory tract infection.
6. Intend to use drugs that are forbidden in combination in this trial plan, or fail to complete the prescribed elimination period for specific prohibited drugs.
7. Has abused alcohol or drugs in the 12 months prior to the day of signing the consent form.
8. Have a history of immunodeficiency diseases, including human immunodeficiency virus (HIV) test results are positive.
9. Alanine transamine enzyme(ALT) or aspartic acid transamine enzyme (AST) concentration≥3 times the upper limit of normal (ULN) at the first visit.
10. Have received immunoglobulin or blood preparations within 30 days before the day of signing the subject's consent form.
11. At the same time participate in other clinical trials.
12. AstraZeneca employees who participated in the planning and/or execution of this trial.
13. The employees of the test institution, other personnel involved in the execution of this test, or the immediate family members of the foregoing personnel.
14. Women who are pregnant, breastfeeding or breastfeeding.
15. Have received Benralizumab treatment in this trial.
16. Simultaneously suffering from primary adrenal insufficiency (Addison's disease), or irreversible secondary adrenal insufficiency due to other independent reasons (such as pituitary gland tumor or its treatment).
17. At the same time suffering from inflammatory diseases, OCS must be used as maintenance treatment for a long time, such as (but not limited to) giant cell arteritis or rheumatic polymyalgia.
18. The exclusion conditions of genetic research include any exclusion conditions of the main experiment or any of the following conditions:
─Have had allogeneic bone marrow transplantation before.
─Have received whole blood transfusion without removing white blood cells within 120 days before the collection of genetic samples.
19. Any disease that has been judged by an experienced host to be unstable, including but not limited to cardiovascular, gastrointestinal, liver, kidney, nerve, musculoskeletal, infection, endocrine, metabolism, blood, mental or major physical damage, and may :
─Affect the safety of patients throughout the entire testing process.
─ Confuse the test results; or may affect the scientific validity of the test data results. Hinder the patient's ability to complete the entire test period.
20. According to the examination host, any clinically abnormal findings in physical examination, medical history, vital signs, hematology, clinical chemistry, or urinalysis during the recruitment period may put the patient at risk due to participation in the examination. Or it may affect the results of the test, or the patient's ability to complete the entire test period.
21. Cancer history. Patients with basal cell carcinoma, localized skin squamous cell carcinoma, or cervical carcinoma in situ can be included in the test if they are in a recovery state and have completed curative treatment at least 12 months before the date of informed consent. Patients with other malignant tumors can be included in the test if they are in a recovery state and have completed curative treatment at least 5 years before the date of obtaining informed consent.
22. During the screening period, any other (non-asthma-related) disease onset or adverse reaction/serious adverse reaction requires temporary use of systemic corticosteroids, increase in the maintenance dose of OCS, or 30 before the second visit (first use of benralizumab) Antibiotics or antiviral drugs are needed within days. However, the screening period is allowed to be extended by 3 months to ensure that the patient recovers from any non-asthma-related illness episodes or adverse reactions/serious adverse reactions.
23. Night shift staff.
The Estimated Number of Participants
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Taiwan
46 participants
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Global
600 participants
