Clinical Trials List
Protocol NumberINS1007-301
NCT Number(ClinicalTrials.gov Identfier)NCT04594369
Completed
2020-11-02 - 2024-04-30
Phase III
Recruiting7
ICD-10J47.9
Bronchiectasis, uncomplicated
ICD-9494.0
Bronchiectasis without acute exacerbation
A phase 3, randomized, double-blind, placebo-controlled trial to evaluate the safety, efficacy, and tolerability of Brensocatib administered once a day to subjects with non-cystic fibrosis bronchiectasis for 52 weeks – ASPEN test
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Sponsor
PPD
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- 蘇茂昌 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 陳鍾岳 Division of Thoracic Medicine
- 許棨逵 Division of Thoracic Medicine
- 邱建通 Division of Thoracic Medicine
- 陳俊榮 Division of Thoracic Medicine
- 李和昇 Division of Thoracic Medicine
- 賴永發 Division of Thoracic Medicine
- 吳俊廷 Division of Thoracic Medicine
- 周柏安 Division of Thoracic Medicine
- Ming-Shyan Huang Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 余文光 Division of Thoracic Medicine
- Jia-Yih Feng Division of Thoracic Medicine
- Kang-Cheng Su Division of Thoracic Medicine
- Wei-Zhi Chen Division of Thoracic Medicine
- 蕭逸函 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Inn-Wen Chong Division of Thoracic Medicine
- Hung-Ling Huang Division of Thoracic Medicine
- 鄭孟軒 Division of Thoracic Medicine
- Hung-Ling Huang Division of Thoracic Medicine
- Ying-Ming Tsai Tsai Division of Thoracic Medicine
- 李玫萱 Division of Thoracic Medicine
- Ming-Ju Tsai Division of Thoracic Medicine
- 陳家閔 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Non-cystic fibrotic bronchiectasis
Objectives
To evaluate the efficacy, safety and tolerability of brensocatib as a treatment for non-cystic fibrosis bronchiectasis (NCFBE).
Test Drug
Brensocatib (INS1007)
Active Ingredient
Brensocatib (INS1007)
Dosage Form
tablet
Dosage
10 mg；25 mg
Endpoints
To assess the effect of brensocatib (10 mg vs. 25 mg) compared to placebo in the rate of pulmonary exacerbation (PE) during a 52-week treatment period
Inclution Criteria
Trial inclusion conditions
Subjects must meet all of the following conditions before they can participate in this trial:
1. Provide the signed informed consent form for the trial.
2. Men or women aged ≥ 18 years and ≤ 85 years (inclusive) at the time of screening (participants in this trial in Taiwan must be at least 20 years old).
3. Body Mass Index (BMI) ≥ 18.5 during screening.
4. Have a clinical history consistent with NCFBE (cough, chronic sputum and/or recurrent respiratory infections), and a Computed Tomography (CT) scan of the chest confirmed to have bronchiectasis affecting one or more lobes (Can be confirmed based on previous chest CT).
a. For each subject, the most recent chest CT scan (but no more than 5 years before the screening date) will be transferred to the central interpretation agency to confirm the diagnosis of NCFBE.
b. If the assessor is unable to interpret the CT scan due to quality issues, a new CT scan will be performed.
c. If the chest CT scan in the past 5 years is not available, a new chest CT scan must be obtained to confirm the NCFBE diagnosis by the central interpretation agency.
5. At the time of screening visits, the National Health and Nutrition Examination Survey (National Health and Nutrition Examination Survey) reference formula is used to calculate that the forced expiratory volume in one second (FEV1) after bronchodilator administration is up to The predicted normal value is ≥ 30%, and the absolute value is ≥ 750 mL.
6. Those who currently have sputum, have a history of chronic sputum expectoration for at least 3 months in the past 12 months, and can provide sputum samples during screening (first visit). If a subject is unable to cough up sputum on their own during screening, the subject will be considered a screening failure. Subjects should not undergo sputum induction procedures in order to meet the inclusion conditions during screening.
7. During the screening visit, the color of mucopurulent or purulent sputum was evaluated according to the color chart developed by MP Murray.
8. In the 12 months before the screening visit, there were at least 2 lung deteriorations. The definition requires a doctor to prescribe antibiotics for the signs and symptoms of respiratory tract infection.
9. From the first day to at least 90 days after the last dose, the woman must have menopause (defined as no menstruation for 12 months and no other medical reasons), surgical sterilization, or use a highly effective double-barrier contraceptive method (That is, the method that can achieve an unexpected pregnancy rate of <1% per year when used in combination). These methods include total abstinence (abstaining heterosexual intersex during the trial period); ovulation-related compound (containing estrogen and progesterone) or progesterone unilateral hormonal contraceptive supplemented by a double barrier method (preferably a male condom) ; Intrauterine contraceptive device; intrauterine hormonal release system; or partner receiving vasectomy. For fertile women ≤ 45 years old, a confirmatory test of the concentration of additional follicle-stimulating hormone (FSH) with a limit of> 40 mIU/mL should be performed before they can be considered as infertile.
Note: Abstinence can only be regarded as a highly effective method of contraception when it conforms to the subject's preference and is a normal lifestyle. Periodic abstinence (calendar method, symptom basal body temperature method, contraception method after ovulation), intercourse interruption method (extracorporeal ejaculation method), spermicide only, and breastfeeding without menstruation are all unacceptable methods of contraception.
10. Male subjects who have fertile female partners must use effective contraceptive methods from day 1 until at least 90 days after the last dose. Acceptable methods include total abstinence (abstaining sexual activity during the trial), ovulation-inhibiting compounds (containing estrogen and progesterone) or progesterone unilateral hormonal contraceptives, intrauterine contraceptive devices, and intrauterine hormone release systems.
Subjects must meet all of the following conditions before they can participate in this trial:
1. Provide the signed informed consent form for the trial.
2. Men or women aged ≥ 18 years and ≤ 85 years (inclusive) at the time of screening (participants in this trial in Taiwan must be at least 20 years old).
3. Body Mass Index (BMI) ≥ 18.5 during screening.
4. Have a clinical history consistent with NCFBE (cough, chronic sputum and/or recurrent respiratory infections), and a Computed Tomography (CT) scan of the chest confirmed to have bronchiectasis affecting one or more lobes (Can be confirmed based on previous chest CT).
a. For each subject, the most recent chest CT scan (but no more than 5 years before the screening date) will be transferred to the central interpretation agency to confirm the diagnosis of NCFBE.
b. If the assessor is unable to interpret the CT scan due to quality issues, a new CT scan will be performed.
c. If the chest CT scan in the past 5 years is not available, a new chest CT scan must be obtained to confirm the NCFBE diagnosis by the central interpretation agency.
5. At the time of screening visits, the National Health and Nutrition Examination Survey (National Health and Nutrition Examination Survey) reference formula is used to calculate that the forced expiratory volume in one second (FEV1) after bronchodilator administration is up to The predicted normal value is ≥ 30%, and the absolute value is ≥ 750 mL.
6. Those who currently have sputum, have a history of chronic sputum expectoration for at least 3 months in the past 12 months, and can provide sputum samples during screening (first visit). If a subject is unable to cough up sputum on their own during screening, the subject will be considered a screening failure. Subjects should not undergo sputum induction procedures in order to meet the inclusion conditions during screening.
7. During the screening visit, the color of mucopurulent or purulent sputum was evaluated according to the color chart developed by MP Murray.
8. In the 12 months before the screening visit, there were at least 2 lung deteriorations. The definition requires a doctor to prescribe antibiotics for the signs and symptoms of respiratory tract infection.
9. From the first day to at least 90 days after the last dose, the woman must have menopause (defined as no menstruation for 12 months and no other medical reasons), surgical sterilization, or use a highly effective double-barrier contraceptive method (That is, the method that can achieve an unexpected pregnancy rate of <1% per year when used in combination). These methods include total abstinence (abstaining heterosexual intersex during the trial period); ovulation-related compound (containing estrogen and progesterone) or progesterone unilateral hormonal contraceptive supplemented by a double barrier method (preferably a male condom) ; Intrauterine contraceptive device; intrauterine hormonal release system; or partner receiving vasectomy. For fertile women ≤ 45 years old, a confirmatory test of the concentration of additional follicle-stimulating hormone (FSH) with a limit of> 40 mIU/mL should be performed before they can be considered as infertile.
Note: Abstinence can only be regarded as a highly effective method of contraception when it conforms to the subject's preference and is a normal lifestyle. Periodic abstinence (calendar method, symptom basal body temperature method, contraception method after ovulation), intercourse interruption method (extracorporeal ejaculation method), spermicide only, and breastfeeding without menstruation are all unacceptable methods of contraception.
10. Male subjects who have fertile female partners must use effective contraceptive methods from day 1 until at least 90 days after the last dose. Acceptable methods include total abstinence (abstaining sexual activity during the trial), ovulation-inhibiting compounds (containing estrogen and progesterone) or progesterone unilateral hormonal contraceptives, intrauterine contraceptive devices, and intrauterine hormone release systems.
Exclusion Criteria
Test exclusion conditions
The trial physician will determine whether you are eligible to participate in this trial. Some reasons you may not be eligible include:
Subjects who meet any of the following conditions will not be eligible for trial participation:
1. According to the judgment of the test leader, the main diagnosis is Chronic Obstructive Pulmonary Disease (COPD) or asthma. If bronchiectasis is the main diagnosis, patients with COPD and/or asthma can be included
2. The subject receives supplemental oxygen for> 12 hours a day.
3. Bronchiectasis caused by cystic fibrosis.
4. Current smokers as defined by the Centers for Disease Control and Prevention (CDC).
5. According to the BE-CT scoring system, there is no evidence of bronchiectasis.
6. According to the test host’s judgment, known or suspected immunodeficiency diseases, including invasive opportunistic infections (for example: tuberculosis (tuberculosis, TB), histoplasmosis, listeriosis, coccidiosis, Pneumocysticercosis, aspergillosis), although the infection has resolved, or there are other recurrent infections with abnormal frequency, or long-term infections that may be in a state of immunocompromised.
7. Known history of human immunodeficiency virus (HIV) infection.
8. Hepatitis B virus infection was confirmed at the time of screening, or the Hepatitis B Surface Antigen (HBsAg) test was positive at the time of screening.
After vaccination, the subjects gained immunity against hepatitis B virus infection (HBsAg negative, Hepatitis B Surface Antibody (HBsAb) positive, and Hepatitis B Core Antibody (HBcAb) negative Of the subjects can meet the qualifications of the trial).
Only when the hepatitis B virus deoxyribonucleic acid (DNA) concentration cannot be measured, subjects who are HBcAb positive can qualify for the test.
9. Hepatitis C Virus (HCV) was diagnosed at the time of screening. Only when the HCV Ribonucleic Acid (RNA) test is negative, subjects who are positive for hepatitis C antibodies are eligible for the test.
10. Currently receiving treatment for Nontuberculous Mycobacteria (NTM) lung infection, allergic pulmonary aspergillosis or TB.
11. Currently suffering from active and symptomatic infection of severe special infectious pneumonia (Coronavirus Disease 2019, COVID-19).
12. During the screening period, technically acceptable spirometers that meet the American Thoracic Society (ATS)/European Respiratory Society (ERS) acceptable standards cannot be performed, including at least 3 At least two of the accepted flow-volume curves meet the ATS/ERS FEV1 repeatability standard.
13. Unable to follow the test procedure (for example: due to language problems or psychological barriers).
14. Are receiving drugs or treatments that are prohibited as concomitant drugs
15. Before the screening visit, start receiving oral or inhaled antibiotics as chronic treatment for NCFBE <3 months.
a. If the subject receives antibiotics as a chronic treatment, the treatment should be used for at least 3 months before being included, while meeting all other inclusion conditions and not meeting any exclusion conditions.
16. Chronic treatment of oral steroids (regardless of indication)
17. Subjects adjusted their baseline drugs within 1 month before screening; they can be rescreened one month after starting new treatment.
18. Abnormal renal function test (estimated value of glomerular filtration rate based on the joint research formula of chronic kidney disease epidemiology <30 mL/min).
19. Active liver disease or liver dysfunction that meets the following conditions:
a. Increased liver function test results (Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST)> 2 x upper limit of normal (ULN)).
b. Bilirubin ＞1.5 x ULN (if bilirubin has been separated and direct bilirubin is <35%, bilirubin alone is allowed to occur ＞1.5 x ULN).
c. Known liver or biliary abnormalities, but excluding Gilbert's syndrome or asymptomatic gallstones.
20. There has been a history of malignant tumors in the past 5 years, but does not include fully cured cervical carcinoma in situ, and fully cured non-metastatic squamous or basal cell skin cancer.
21. Participated in clinical trials of brensocatib.
22. Absolute neutrophil count at screening visit <1,000/mm3.
23. Have received any active attenuated vaccine within 4 weeks before the first administration of brensocatib. If a live vaccine has been vaccinated, the subject should wait 4 weeks before being screened. During the trial period, subjects shall not receive any active attenuated vaccine.
24. Significant hemoptysis (≥ 300 mL or blood transfusion required) within 6 weeks before screening visit or during screening.
25. Have been diagnosed with periodontal disease and meet any of the following conditions:
a. The condition is being treated continuously by a dentist, or
b. It is expected to undergo periodontal disease related procedures during the trial period.
26. Deterioration occurred within 4 weeks before screening or during screening. In this case, the subject will be considered a screening failure. Subjects can only be re-screened after recovery and 4 weeks after the last dose of antibiotic treatment.
27. During the screening period, unable to follow the instructions to complete the electronic log ≥ 75%, or there is a compliance problem.
28. Participated in any other interventional clinical trials within 3 months before the screening visit.
29. Clinically diagnosed with Papillon-Lefevre syndrome.
30. At the same time suffering from a severe disease, as judged by the test host, it will adversely affect the participants' participation in the test. Examples include, but are not limited to, short life expectancy, poorly controlled diabetes, cardiovascular disease (e.g., New York Heart Association (NYHA) grade III or IV heart failure), severe kidney disease (e.g., severe renal disease syndrome) ), hepatobiliary disease (for example: Child-Pugh grade B or C), neurological disease (for example: demyelinating disease), active major autoimmune disease (for example: lupus, inflammatory bowel disease, rheumatoid arthritis Etc.), other severe endocrine, gastrointestinal, metabolic, pulmonary or lymphatic diseases. The specific reasons for excluding subjects based on this condition will be recorded in the trial documents (medical records, case report forms (Case Report Form, CRF), etc.).
31. There are any clinically significant abnormal laboratory values at the time of screening, or suffering from diseases or illnesses (for example: severe COVID-19 disease survivors, including acute respiratory distress syndrome (Acute Respiratory Distress Syndrome, ARDS), cardiovascular, pulmonary disease) , Gastrointestinal tract, liver, kidney, nerve, musculoskeletal, endocrine, metabolic, mental, physical disorders, or lung transplantation), and the trial host determines that participation in the trial may put the subject at risk or interfere with the subject The patient’s treatment, evaluation, or influence the results of the trial, or cause compliance issues with the trial, or plan or anticipate major surgical procedures during the trial.
32. There was a history of alcohol or drug abuse within 6 months before the screening visit.
33. There are any other medical or psychological conditions at the time of screening, including abnormal laboratory test results, which are determined by the test host as showing a new and/or under-recognized disease, and may be due to the participation of test subjects The unreasonable risks caused by this clinical trial may make the participation of subjects unreliable or may interfere with the evaluation of the trial. The specific reasons for excluding subjects based on this condition will be recorded in the trial file.
34. Is the trial host, or any co-host, research assistant, pharmacist, trial coordinator, other staff or their relatives directly involved in the execution of the trial.
The trial physician will determine whether you are eligible to participate in this trial. Some reasons you may not be eligible include:
Subjects who meet any of the following conditions will not be eligible for trial participation:
1. According to the judgment of the test leader, the main diagnosis is Chronic Obstructive Pulmonary Disease (COPD) or asthma. If bronchiectasis is the main diagnosis, patients with COPD and/or asthma can be included
2. The subject receives supplemental oxygen for> 12 hours a day.
3. Bronchiectasis caused by cystic fibrosis.
4. Current smokers as defined by the Centers for Disease Control and Prevention (CDC).
5. According to the BE-CT scoring system, there is no evidence of bronchiectasis.
6. According to the test host’s judgment, known or suspected immunodeficiency diseases, including invasive opportunistic infections (for example: tuberculosis (tuberculosis, TB), histoplasmosis, listeriosis, coccidiosis, Pneumocysticercosis, aspergillosis), although the infection has resolved, or there are other recurrent infections with abnormal frequency, or long-term infections that may be in a state of immunocompromised.
7. Known history of human immunodeficiency virus (HIV) infection.
8. Hepatitis B virus infection was confirmed at the time of screening, or the Hepatitis B Surface Antigen (HBsAg) test was positive at the time of screening.
After vaccination, the subjects gained immunity against hepatitis B virus infection (HBsAg negative, Hepatitis B Surface Antibody (HBsAb) positive, and Hepatitis B Core Antibody (HBcAb) negative Of the subjects can meet the qualifications of the trial).
Only when the hepatitis B virus deoxyribonucleic acid (DNA) concentration cannot be measured, subjects who are HBcAb positive can qualify for the test.
9. Hepatitis C Virus (HCV) was diagnosed at the time of screening. Only when the HCV Ribonucleic Acid (RNA) test is negative, subjects who are positive for hepatitis C antibodies are eligible for the test.
10. Currently receiving treatment for Nontuberculous Mycobacteria (NTM) lung infection, allergic pulmonary aspergillosis or TB.
11. Currently suffering from active and symptomatic infection of severe special infectious pneumonia (Coronavirus Disease 2019, COVID-19).
12. During the screening period, technically acceptable spirometers that meet the American Thoracic Society (ATS)/European Respiratory Society (ERS) acceptable standards cannot be performed, including at least 3 At least two of the accepted flow-volume curves meet the ATS/ERS FEV1 repeatability standard.
13. Unable to follow the test procedure (for example: due to language problems or psychological barriers).
14. Are receiving drugs or treatments that are prohibited as concomitant drugs
15. Before the screening visit, start receiving oral or inhaled antibiotics as chronic treatment for NCFBE <3 months.
a. If the subject receives antibiotics as a chronic treatment, the treatment should be used for at least 3 months before being included, while meeting all other inclusion conditions and not meeting any exclusion conditions.
16. Chronic treatment of oral steroids (regardless of indication)
17. Subjects adjusted their baseline drugs within 1 month before screening; they can be rescreened one month after starting new treatment.
18. Abnormal renal function test (estimated value of glomerular filtration rate based on the joint research formula of chronic kidney disease epidemiology <30 mL/min).
19. Active liver disease or liver dysfunction that meets the following conditions:
a. Increased liver function test results (Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST)> 2 x upper limit of normal (ULN)).
b. Bilirubin ＞1.5 x ULN (if bilirubin has been separated and direct bilirubin is <35%, bilirubin alone is allowed to occur ＞1.5 x ULN).
c. Known liver or biliary abnormalities, but excluding Gilbert's syndrome or asymptomatic gallstones.
20. There has been a history of malignant tumors in the past 5 years, but does not include fully cured cervical carcinoma in situ, and fully cured non-metastatic squamous or basal cell skin cancer.
21. Participated in clinical trials of brensocatib.
22. Absolute neutrophil count at screening visit <1,000/mm3.
23. Have received any active attenuated vaccine within 4 weeks before the first administration of brensocatib. If a live vaccine has been vaccinated, the subject should wait 4 weeks before being screened. During the trial period, subjects shall not receive any active attenuated vaccine.
24. Significant hemoptysis (≥ 300 mL or blood transfusion required) within 6 weeks before screening visit or during screening.
25. Have been diagnosed with periodontal disease and meet any of the following conditions:
a. The condition is being treated continuously by a dentist, or
b. It is expected to undergo periodontal disease related procedures during the trial period.
26. Deterioration occurred within 4 weeks before screening or during screening. In this case, the subject will be considered a screening failure. Subjects can only be re-screened after recovery and 4 weeks after the last dose of antibiotic treatment.
27. During the screening period, unable to follow the instructions to complete the electronic log ≥ 75%, or there is a compliance problem.
28. Participated in any other interventional clinical trials within 3 months before the screening visit.
29. Clinically diagnosed with Papillon-Lefevre syndrome.
30. At the same time suffering from a severe disease, as judged by the test host, it will adversely affect the participants' participation in the test. Examples include, but are not limited to, short life expectancy, poorly controlled diabetes, cardiovascular disease (e.g., New York Heart Association (NYHA) grade III or IV heart failure), severe kidney disease (e.g., severe renal disease syndrome) ), hepatobiliary disease (for example: Child-Pugh grade B or C), neurological disease (for example: demyelinating disease), active major autoimmune disease (for example: lupus, inflammatory bowel disease, rheumatoid arthritis Etc.), other severe endocrine, gastrointestinal, metabolic, pulmonary or lymphatic diseases. The specific reasons for excluding subjects based on this condition will be recorded in the trial documents (medical records, case report forms (Case Report Form, CRF), etc.).
31. There are any clinically significant abnormal laboratory values at the time of screening, or suffering from diseases or illnesses (for example: severe COVID-19 disease survivors, including acute respiratory distress syndrome (Acute Respiratory Distress Syndrome, ARDS), cardiovascular, pulmonary disease) , Gastrointestinal tract, liver, kidney, nerve, musculoskeletal, endocrine, metabolic, mental, physical disorders, or lung transplantation), and the trial host determines that participation in the trial may put the subject at risk or interfere with the subject The patient’s treatment, evaluation, or influence the results of the trial, or cause compliance issues with the trial, or plan or anticipate major surgical procedures during the trial.
32. There was a history of alcohol or drug abuse within 6 months before the screening visit.
33. There are any other medical or psychological conditions at the time of screening, including abnormal laboratory test results, which are determined by the test host as showing a new and/or under-recognized disease, and may be due to the participation of test subjects The unreasonable risks caused by this clinical trial may make the participation of subjects unreliable or may interfere with the evaluation of the trial. The specific reasons for excluding subjects based on this condition will be recorded in the trial file.
34. Is the trial host, or any co-host, research assistant, pharmacist, trial coordinator, other staff or their relatives directly involved in the execution of the trial.
The Estimated Number of Participants
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Taiwan
26 participants
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Global
1620 participants
