Clinical Trials List
Protocol NumberEFC18244
NCT Number(ClinicalTrials.gov Identfier)NCT07190222
Active
2025-11-01 - 2030-12-31
Phase II
Not yet recruiting1
Recruiting7
A phase 2b/3, randomized, double-blind, placebo-controlled, multicenter trial was conducted to investigate the efficacy and safety of lunsekimig in adult subjects with poorly controlled chronic obstructive pulmonary disease (COPD) of the eosinophilic leukocytosis phenotype.
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Trial Applicant
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Sponsor
Sanofi Inc.
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Trial scale
Multi-Regional Multi-Center
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Update
2026/07/03
Investigators and Locations
Co-Principal Investigator
- jong rung Tsai 無
- Inn-Wen Chong 無
- Wei-An Chang 無
- 鄭孟軒 無
- Ming-Ju Tsai 無
- 陳家閔 無
- 鄭至宏 無
- Hung-Ling Huang 無
- 莊政皓 無
- 李岱晃 無
- 張旭良 無
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
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
Co-Principal Investigator
- 蕭慈慧 無
- KUANG-YAO YANG 無
- Wei-Zhi Chen 無
- 潘聖衛 無
- 蕭逸函 無
- 余文光 無
- 孫傳硯 無
- 張芝榕 無
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Horng-Chyuan Lin
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
The efficacy of lunsekimig was assessed by measuring the annualized incidence of moderate to severe COPD exacerbations.
Objectives
This is a parallel, phase 2/3, 3-group trial designed to investigate the efficacy, safety, and tolerability of lunsekimig subcutaneous (SC) treatment versus placebo in adult subjects (aged 40 to 80 years) with poorly controlled eosinophilic COPD.
Test Drug
Lunsekimig/ SAR443765
Active Ingredient
Lunsekimig/ SAR443765
Dosage Form
Prefilled Injectable
Dosage
300 mg/2mL
Endpoints
The efficacy of lunsekimig was assessed by measuring the annualized incidence of moderate to severe COPD exacerbations.
Inclution Criteria
Age
I 01. Participants must be between 40 and 80 years of age (inclusive) when signing the participant consent form. In countries where the legal age of adulthood is over 18, the participant's legally authorized representative (LAR) must also sign a specific informed consent form (ICF).
Participant Type and Disease Characteristics
I 02. A physician-diagnosed history of COPD for at least one year prior to screening, classified as moderate to very severe, with an FEV1/FVC ratio less than 0.70 (<0.70) at the time of screening (first follow-up visit) after bronchodilator use, and an FEV1 greater than or equal to 20% (≥20%) and less than or equal to 70% (≤70%) of the expected normal value after bronchodilator use.
I 03. Current or past smoker with a smoking history of 10 (≥10) pack-years.
I 04. A CAAT score greater than or equal to 10 (≥10) at screening (first follow-up visit).
I 05. A history of high risk of exacerbation, with ≥2 (≥2) moderate exacerbations or ≥1 (≥1) severe exacerbation within one year prior to screening (first follow-up visit).
*A moderate exacerbation is recorded by the trial administrator and is defined as AECOPD requiring at least 3 days of systemic corticosteroids (or an equivalent exposure dose†) and/or antibiotics (see Section 10.11.1). At least one of the two necessary moderate exacerbations must require systemic corticosteroids.
†Includes formulations that provide at least 3 days of systemic corticosteroid exposure.
**Severe exacerbations are recorded by the trial administrator and are defined as AECOPD requiring hospitalization or visit to the emergency room (or emergency care facility) for more than 24 hours (>24).
To count two moderate and severe events as independent events, there must be at least a 14-day interval between any systemic steroid/antibiotic treatment courses for these two events, or, if hospitalization is required (for severe AECOPD events only), a 14-day interval between discharge and readmission.
I 06. Subjects must have received triple-drug control therapy (LABA+LAMA+ICS) for at least 12 weeks prior to randomization and a stable dose of medication for ≥4 weeks prior to screening (first follow-up visit). Furthermore, there must have been at least one exacerbation during the current treatment course (LABA+LAMA dual control therapy is permitted if ICS is contraindicated).
I 07. Evidence of type 2 (T2) inflammation: Subjects with an eosinophil count of ≥150 cells/μL at screening (first follow-up visit). Weight
I 08. Body mass index (BMI) between 18.0 (inclusive) and 40.0 (inclusive) kg/m², and weight at screening (first follow-up visit) must not be less than 40.0 kg.
Sexual Behavior, Contraception/Barrier Methods, and Pregnancy Testing Requirements/Breastfeeding
I 09. All contraceptive methods used by both men and women should comply with local regulations regarding contraceptive methods used by participants in the clinical trial. a) Male Participants:
Male participants are eligible to participate if they agree to adhere to the following guidelines during the trial treatment and for at least 8 weeks after the last dose of the trial treatment:
• Prohibition of sperm donation or cryopreservation
In addition, one of the following:
- Avoidance of sexual intercourse with the opposite sex (if this is consistent with their preferred and usual lifestyle; i.e., long-term and continuous abstinence), and consent to continued abstinence
Or
- Must consent to the use of contraception/barrier methods, detailed below
- When engaging in sexual intercourse with a currently non-pregnant, fertile woman (WOCBP), use male condoms as described in Appendix 4 (Section 10.4: Guidelines for Contraception and Barrier Methods) and another highly effective method of contraception.
b) Female Participants:
• Female participants are eligible to participate if they are not pregnant or breastfeeding and meet one of the following criteria:
- Being a non-fertile woman (WONCBP), as defined in Appendix 4 (Section 10.4: Guidelines for Contraception and Barrier Methods). Alternatively
- For WOCBP and consent to use a highly effective (less than 1% annual failure rate [<1%]) and low-user-dependency method of contraception during the trial treatment period (before starting treatment) and for at least 8 weeks after the last dose of the trial treatment, as described in Appendix 4 (Section 10.4: Guidelines for Contraception and Barrier Methods), and consent not to donate or cryopreserve oocytes (eggs, ovules) for fertility purposes during this period.
• The high-sensitivity pregnancy test result for WOCBP must be negative. Serum pregnancy testing will be performed at screening (first visit), and urine pregnancy testing will be performed before the first dose of the investigational drug (second visit), at the early discontinuation visit, and at the EOS (16th visit) (see Section 8.4.5).
- Urine pregnancy testing will be performed before each IMP dose until the EOS visit.
Informed Consent
I 10. Able to provide signed participant consent forms as described in Appendix 1 of this trial plan, including compliance with the Participant Consent Form (ICF) and the requirements and limitations listed in this trial plan.
I 01. Participants must be between 40 and 80 years of age (inclusive) when signing the participant consent form. In countries where the legal age of adulthood is over 18, the participant's legally authorized representative (LAR) must also sign a specific informed consent form (ICF).
Participant Type and Disease Characteristics
I 02. A physician-diagnosed history of COPD for at least one year prior to screening, classified as moderate to very severe, with an FEV1/FVC ratio less than 0.70 (<0.70) at the time of screening (first follow-up visit) after bronchodilator use, and an FEV1 greater than or equal to 20% (≥20%) and less than or equal to 70% (≤70%) of the expected normal value after bronchodilator use.
I 03. Current or past smoker with a smoking history of 10 (≥10) pack-years.
I 04. A CAAT score greater than or equal to 10 (≥10) at screening (first follow-up visit).
I 05. A history of high risk of exacerbation, with ≥2 (≥2) moderate exacerbations or ≥1 (≥1) severe exacerbation within one year prior to screening (first follow-up visit).
*A moderate exacerbation is recorded by the trial administrator and is defined as AECOPD requiring at least 3 days of systemic corticosteroids (or an equivalent exposure dose†) and/or antibiotics (see Section 10.11.1). At least one of the two necessary moderate exacerbations must require systemic corticosteroids.
†Includes formulations that provide at least 3 days of systemic corticosteroid exposure.
**Severe exacerbations are recorded by the trial administrator and are defined as AECOPD requiring hospitalization or visit to the emergency room (or emergency care facility) for more than 24 hours (>24).
To count two moderate and severe events as independent events, there must be at least a 14-day interval between any systemic steroid/antibiotic treatment courses for these two events, or, if hospitalization is required (for severe AECOPD events only), a 14-day interval between discharge and readmission.
I 06. Subjects must have received triple-drug control therapy (LABA+LAMA+ICS) for at least 12 weeks prior to randomization and a stable dose of medication for ≥4 weeks prior to screening (first follow-up visit). Furthermore, there must have been at least one exacerbation during the current treatment course (LABA+LAMA dual control therapy is permitted if ICS is contraindicated).
I 07. Evidence of type 2 (T2) inflammation: Subjects with an eosinophil count of ≥150 cells/μL at screening (first follow-up visit). Weight
I 08. Body mass index (BMI) between 18.0 (inclusive) and 40.0 (inclusive) kg/m², and weight at screening (first follow-up visit) must not be less than 40.0 kg.
Sexual Behavior, Contraception/Barrier Methods, and Pregnancy Testing Requirements/Breastfeeding
I 09. All contraceptive methods used by both men and women should comply with local regulations regarding contraceptive methods used by participants in the clinical trial. a) Male Participants:
Male participants are eligible to participate if they agree to adhere to the following guidelines during the trial treatment and for at least 8 weeks after the last dose of the trial treatment:
• Prohibition of sperm donation or cryopreservation
In addition, one of the following:
- Avoidance of sexual intercourse with the opposite sex (if this is consistent with their preferred and usual lifestyle; i.e., long-term and continuous abstinence), and consent to continued abstinence
Or
- Must consent to the use of contraception/barrier methods, detailed below
- When engaging in sexual intercourse with a currently non-pregnant, fertile woman (WOCBP), use male condoms as described in Appendix 4 (Section 10.4: Guidelines for Contraception and Barrier Methods) and another highly effective method of contraception.
b) Female Participants:
• Female participants are eligible to participate if they are not pregnant or breastfeeding and meet one of the following criteria:
- Being a non-fertile woman (WONCBP), as defined in Appendix 4 (Section 10.4: Guidelines for Contraception and Barrier Methods). Alternatively
- For WOCBP and consent to use a highly effective (less than 1% annual failure rate [<1%]) and low-user-dependency method of contraception during the trial treatment period (before starting treatment) and for at least 8 weeks after the last dose of the trial treatment, as described in Appendix 4 (Section 10.4: Guidelines for Contraception and Barrier Methods), and consent not to donate or cryopreserve oocytes (eggs, ovules) for fertility purposes during this period.
• The high-sensitivity pregnancy test result for WOCBP must be negative. Serum pregnancy testing will be performed at screening (first visit), and urine pregnancy testing will be performed before the first dose of the investigational drug (second visit), at the early discontinuation visit, and at the EOS (16th visit) (see Section 8.4.5).
- Urine pregnancy testing will be performed before each IMP dose until the EOS visit.
Informed Consent
I 10. Able to provide signed participant consent forms as described in Appendix 1 of this trial plan, including compliance with the Participant Consent Form (ICF) and the requirements and limitations listed in this trial plan.
Exclusion Criteria
Medical Condition
E 01. Currently diagnosed with asthma or has a documented history of asthma, including childhood asthma and documented asthma-COPD overlap syndrome (ACOS), in accordance with the 2024 Global Initiative for Asthma (GINA) guidelines (1) or other recognized guidelines.
E 02. Has a significant, physician-diagnosed lung disease other than COPD (e.g., pulmonary fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, bronchiectasis, eosinophilic granulomatosis with polyangiitis), or is diagnosed with other lung or systemic diseases associated with elevated peripheral blood eosinophil counts.
E 03. Receives prolonged oxygen therapy at a flow rate greater than 4.0 (>4.0) L/min, or requires an oxygen flow rate greater than 2.0 (>2.0) L/min to maintain resting oxygen saturation greater than 88% (>88%). E 04. Hypercapnia requiring bi-level positive airway pressure (BiPAP). Obstructive sleep apnea syndrome (OSAS) without hypercapnia precludes the use of continuous positive airway pressure (CPAP).
E 05. Subject adherence to controller medication (i.e., LABA+LAMA+ICS, see Section 6.9.2.1) is less than 80% (<80%) during the screening period.
E 06. AECOPD occurring within 4 weeks prior to or during the screening period. If a subject develops AECOPD during the screening period, the screening period may be extended by up to 12 weeks to ensure randomization (second visit) is not performed until 4 weeks after completion of AECOPD treatment (systemic corticosteroids or antibiotics).
E 07. Clinically symptomatic respiratory infection occurring within 4 weeks prior to or during screening. If a subject develops a respiratory infection during screening, the screening period may be extended by up to 12 weeks to ensure randomization (second visit) is not performed until 4 weeks after completion of treatment or symptom stabilization (whichever occurs later).
E 08. Confirmed COVID-19 infection at screening (first visit), screening, or randomization (second visit); these subjects may be rescreened 4 weeks after symptom relief, or 4 weeks after a positive test result if asymptomatic at and after testing.
E 09. Has undergone or plans to undergo pneumonectomy or lung volume reduction surgery.
E 10. Subjects are in the acute phase of a pulmonary rehabilitation program, meaning they have started rehabilitation less than 4 (<4) weeks prior to screening (Note: Subjects in the maintenance phase of a rehabilitation program may be included).
E 11. Diagnosed with alpha-1 antitrypsin deficiency.
E 12. Subjects have a history of clinically significant kidney, liver, cardiovascular, metabolic, neurological, hematological, ocular, respiratory, gastrointestinal, or cerebrovascular disease, drug and/or alcohol abuse, or a history of malignancy or active malignancy, including lymphoproliferative disorders (excluding successfully treated cervical carcinoma in situ, non-metastatic squamous cell or basal cell carcinoma of the skin), or other major medical conditions or illnesses that, in the assessment of the trial administrator, may interfere with the trial or require treatment that may interfere with the trial. Specific examples include (but are not limited to) poorly controlled insulin-dependent diabetes mellitus and uncontrolled hypertension.
E 13. Subjects have undergone major surgery within 8 weeks prior to screening (first follow-up visit).
E 14. Subjects have a history of severe systemic anaphylactic reaction or anaphylactic shock to any biologic agent (including any excipients).
E 15. Pulmonary heart disease or evidence of right heart failure.
E 16. Clinically significant ECG abnormalities at randomization (second follow-up visit) that, in the trial administrator's opinion, may affect trial execution, including prolonged QTc intervals (greater than 450 msec for men and greater than 470 msec for women, using the Fridericia correction formula).
E 17. Open tuberculosis or nontuberculous mycobacterial infection, untreated latent tuberculosis, or a history of incompletely treated tuberculosis. Unless a specialist clearly states that the subject has received appropriate treatment, and the subject may begin biologic therapy based on the medical judgment of the trial administrator and/or infectious disease specialist (see Section 10.2).
E 18. An acute myocardial infarction occurred within 6 months (< 6 months) prior to screening (first follow-up visit).
E 19. A transient ischemic attack or stroke has occurred within 6 months prior to screening (first follow-up visit).
E 20. Hospitalization for any cardiovascular (CV) or cerebrovascular event has occurred within 6 months prior to screening (first follow-up visit).
E 21. New York Heart Association (NYHA) grade III or IV heart failure.
E 22. Patients with arrhythmias, including paroxysmal (e.g., intermittent) atrial fibrillation, will be excluded. Subjects with persistent atrial fibrillation, defined as persistent atrial fibrillation for at least 6 months, and controlled for at least 6 months using a tachycardia control strategy (i.e., selective beta-blockers, calcium channel blockers, pacemaker placement, digoxin, or ablation therapy) and a stable, appropriate concentration of anticoagulant, may be considered for inclusion.
E 23. Patients with unstable ischemic heart disease or other related cardiovascular diseases (e.g., pulmonary embolism, deep vein thrombosis) within the 6 months prior to enrollment (≤6 months), whose condition, as determined by the trial administrator, may place the subject at risk or negatively impact the trial results.
E 24. Women who are breastfeeding, currently breastfeeding, or pregnant.
E 25. Patients diagnosed with active parasitic infection (helminth infection), suspected of having, or at high risk of having a parasitic infection, except those whose active infection has been ruled out by clinical and (if necessary) laboratory evaluation prior to randomization.
E 26. Patients with a known or suspected history of immunosuppression, including a history of invasive opportunistic infections (e.g., histoplasmosis, listeriosis, coccidioidomycosis, Pneumocystis jirovecii infection, or aspergillosis), even if the infection has resolved; or, as determined by the trial administrator, unusually frequent, recurrent, or prolonged infections.
E 27. Evidence of acute or chronic infection requiring treatment with antibiotics, antivirals, antifungals, antiparasitics, or antiprotozoal agents within 4 weeks prior to screening (first follow-up visit); or significant viral infection within 4 weeks prior to screening (first follow-up visit), regardless of the type of antiviral treatment (e.g., symptomatic treatment only for influenza).
E 28. Subjects with active autoimmune disease, or subjects using immunosuppressive therapy to treat autoimmune disease (e.g., inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis).
Previous use/combined treatment (see Section 10.2)
E 29. Received a live attenuated vaccine within 12 weeks prior to screening (first follow-up visit), or a live attenuated vaccine is planned for the entire trial period, and an inactive vaccine (including RNA vaccines) within 2 weeks prior to screening (first follow-up visit) and during screening (see Table 6 for a list of permitted, restricted, and prohibited drugs, and Section 10.11.4 for a list of prohibited live attenuated vaccines).
E 30. Subjects receiving long-term macrolide (e.g., azithromycin) therapy, unless they have received stable therapy for more than 6 (>6) months prior to screening (first follow-up visit) and experienced at least one exacerbation during this course of treatment. Macrolides are permitted for COPD exacerbations throughout the trial period.
E 31. Subjects receiving phosphodiesterase type 3 (PDE-3) inhibitors (e.g., ensifentrine) or phosphodiesterase type 4 (PDE-4) inhibitors (e.g., roflumislast) therapy, unless they have received stable therapy for more than 6 (>6) months prior to screening (first follow-up visit).
E 32. Subjects receiving xanthine/methylxanthine medications (e.g., theophylline) within 4 weeks prior to screening (first follow-up visit).
E 33. Received anti-IgE therapy (e.g., omalizumab [Xolair®]) within 130 days prior to screening (first follow-up visit), or received any other biologic therapy (including anti-IL-4/interleukin-4 receptor [IL-4R], IL-5/interleukin-5 receptor [IL-5R], IL-13, or TSLP) or systemic immunosuppressant (e.g., methotrexate) for inflammatory or autoimmune diseases (e.g., rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, or multiple sclerosis) and other conditions (see Table 6).
E 34. The subject is currently receiving COPD control medication that is not locally approved for the treatment of COPD, or is receiving medications or therapies that are prohibited as concomitant therapy (see Table 6).
Previous/Concurrent Clinical Trial Experience
E 35. Currently enrolled or previously involved in another investigational trial, and receiving investigational treatment (e.g., drugs, vaccines, or invasive devices) within the timeframe specified in Table 6.
Diagnostic Assessment
E 36. History of human immunodeficiency virus (HIV) infection, or a positive HIV serological test for HIV type 1 (HIV-1)/HIV type 2 (HIV-2), or a positive HIV deoxyribonucleic acid (DNA) test at screening (first follow-up visit).
E 37. Subjects show any of the following results at screening:
- Positive for Hepatitis B surface antigen (HBsAg) (or inconclusive),
or
- Positive for immunoglobulin M antibody against Hepatitis B core antigen (IgM HBcAb),
- Positive for total Hepatitis B core antibody (HBcAb) as confirmed by a positive result for Hepatitis B virus (HBV) DNA,
or
- Positive for HCV antibody (Ab) as confirmed by a positive result for Hepatitis C virus (HCV) RNA.
For guidance on interpreting hepatitis serological eligibility, please refer to Table 16 in Section 10.7.5.
E 38. Clinically significant laboratory tests at screening (first follow-up visit):
- Alanine transaminase (ALT) or aspartate aminotransferase (AST) above (>) 2 times the upper limit of normal (ULN).
- Serum total bilirubin greater than 1.5 times the ULN (if the subject has Gilbert's syndrome and total bilirubin is greater than 1.5 times the ULN, direct bilirubin less than 1.5 times the ULN is sufficient for inclusion in the trial).
- Heme levels less than 10 times the ULN in men and less than 9 times the ULN in women. - Neutrophil count less than 1500 (<1500)/μL (less than 1000 (<1000)/μL for African Americans).
- Platelet count less than 100,000 (<100,000)/μL.
- Creatinine greater than or equal to 150 (≥150) μmol/L.
Other Exclusion Criteria
E 39. Subjects who withdraw their consent before enrollment/randomization (second follow-up visit), despite prior screening, will be suspended from enrollment/randomization at the trial level.
E 40. Individuals detained in an institution due to regulatory or legal orders; prisoners or subjects lawfully detained.
E 41. Subjects deemed unsuitable for the trial by the trial administrator, regardless of the reason, including medical or clinical conditions, or who may be at risk of non-compliance with trial procedures.
E 42. Inability to comply with trial procedures (e.g., due to language problems, psychological barriers), or inability to read, understand, and complete questionnaires or use electronic diaries without assistance.
E 43. The subject is an employee of the clinical trial center, another person directly involved in conducting the trial, or an immediate family member of such person (see Section 1.61, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, ICH - Good Clinical Practice (GCP) Regulation E6).
E 44. Allergy to any investigational drug or its components, or a history of drug or other allergies, which the trial administrator deems unsuitable for participation.
E 45. Subjects may be unable to participate in this trial due to any country-specific regulations - see Appendix 7 (Section 3.1: Country-Specific/Regional Requirements).
E 01. Currently diagnosed with asthma or has a documented history of asthma, including childhood asthma and documented asthma-COPD overlap syndrome (ACOS), in accordance with the 2024 Global Initiative for Asthma (GINA) guidelines (1) or other recognized guidelines.
E 02. Has a significant, physician-diagnosed lung disease other than COPD (e.g., pulmonary fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension, bronchiectasis, eosinophilic granulomatosis with polyangiitis), or is diagnosed with other lung or systemic diseases associated with elevated peripheral blood eosinophil counts.
E 03. Receives prolonged oxygen therapy at a flow rate greater than 4.0 (>4.0) L/min, or requires an oxygen flow rate greater than 2.0 (>2.0) L/min to maintain resting oxygen saturation greater than 88% (>88%). E 04. Hypercapnia requiring bi-level positive airway pressure (BiPAP). Obstructive sleep apnea syndrome (OSAS) without hypercapnia precludes the use of continuous positive airway pressure (CPAP).
E 05. Subject adherence to controller medication (i.e., LABA+LAMA+ICS, see Section 6.9.2.1) is less than 80% (<80%) during the screening period.
E 06. AECOPD occurring within 4 weeks prior to or during the screening period. If a subject develops AECOPD during the screening period, the screening period may be extended by up to 12 weeks to ensure randomization (second visit) is not performed until 4 weeks after completion of AECOPD treatment (systemic corticosteroids or antibiotics).
E 07. Clinically symptomatic respiratory infection occurring within 4 weeks prior to or during screening. If a subject develops a respiratory infection during screening, the screening period may be extended by up to 12 weeks to ensure randomization (second visit) is not performed until 4 weeks after completion of treatment or symptom stabilization (whichever occurs later).
E 08. Confirmed COVID-19 infection at screening (first visit), screening, or randomization (second visit); these subjects may be rescreened 4 weeks after symptom relief, or 4 weeks after a positive test result if asymptomatic at and after testing.
E 09. Has undergone or plans to undergo pneumonectomy or lung volume reduction surgery.
E 10. Subjects are in the acute phase of a pulmonary rehabilitation program, meaning they have started rehabilitation less than 4 (<4) weeks prior to screening (Note: Subjects in the maintenance phase of a rehabilitation program may be included).
E 11. Diagnosed with alpha-1 antitrypsin deficiency.
E 12. Subjects have a history of clinically significant kidney, liver, cardiovascular, metabolic, neurological, hematological, ocular, respiratory, gastrointestinal, or cerebrovascular disease, drug and/or alcohol abuse, or a history of malignancy or active malignancy, including lymphoproliferative disorders (excluding successfully treated cervical carcinoma in situ, non-metastatic squamous cell or basal cell carcinoma of the skin), or other major medical conditions or illnesses that, in the assessment of the trial administrator, may interfere with the trial or require treatment that may interfere with the trial. Specific examples include (but are not limited to) poorly controlled insulin-dependent diabetes mellitus and uncontrolled hypertension.
E 13. Subjects have undergone major surgery within 8 weeks prior to screening (first follow-up visit).
E 14. Subjects have a history of severe systemic anaphylactic reaction or anaphylactic shock to any biologic agent (including any excipients).
E 15. Pulmonary heart disease or evidence of right heart failure.
E 16. Clinically significant ECG abnormalities at randomization (second follow-up visit) that, in the trial administrator's opinion, may affect trial execution, including prolonged QTc intervals (greater than 450 msec for men and greater than 470 msec for women, using the Fridericia correction formula).
E 17. Open tuberculosis or nontuberculous mycobacterial infection, untreated latent tuberculosis, or a history of incompletely treated tuberculosis. Unless a specialist clearly states that the subject has received appropriate treatment, and the subject may begin biologic therapy based on the medical judgment of the trial administrator and/or infectious disease specialist (see Section 10.2).
E 18. An acute myocardial infarction occurred within 6 months (< 6 months) prior to screening (first follow-up visit).
E 19. A transient ischemic attack or stroke has occurred within 6 months prior to screening (first follow-up visit).
E 20. Hospitalization for any cardiovascular (CV) or cerebrovascular event has occurred within 6 months prior to screening (first follow-up visit).
E 21. New York Heart Association (NYHA) grade III or IV heart failure.
E 22. Patients with arrhythmias, including paroxysmal (e.g., intermittent) atrial fibrillation, will be excluded. Subjects with persistent atrial fibrillation, defined as persistent atrial fibrillation for at least 6 months, and controlled for at least 6 months using a tachycardia control strategy (i.e., selective beta-blockers, calcium channel blockers, pacemaker placement, digoxin, or ablation therapy) and a stable, appropriate concentration of anticoagulant, may be considered for inclusion.
E 23. Patients with unstable ischemic heart disease or other related cardiovascular diseases (e.g., pulmonary embolism, deep vein thrombosis) within the 6 months prior to enrollment (≤6 months), whose condition, as determined by the trial administrator, may place the subject at risk or negatively impact the trial results.
E 24. Women who are breastfeeding, currently breastfeeding, or pregnant.
E 25. Patients diagnosed with active parasitic infection (helminth infection), suspected of having, or at high risk of having a parasitic infection, except those whose active infection has been ruled out by clinical and (if necessary) laboratory evaluation prior to randomization.
E 26. Patients with a known or suspected history of immunosuppression, including a history of invasive opportunistic infections (e.g., histoplasmosis, listeriosis, coccidioidomycosis, Pneumocystis jirovecii infection, or aspergillosis), even if the infection has resolved; or, as determined by the trial administrator, unusually frequent, recurrent, or prolonged infections.
E 27. Evidence of acute or chronic infection requiring treatment with antibiotics, antivirals, antifungals, antiparasitics, or antiprotozoal agents within 4 weeks prior to screening (first follow-up visit); or significant viral infection within 4 weeks prior to screening (first follow-up visit), regardless of the type of antiviral treatment (e.g., symptomatic treatment only for influenza).
E 28. Subjects with active autoimmune disease, or subjects using immunosuppressive therapy to treat autoimmune disease (e.g., inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, multiple sclerosis).
Previous use/combined treatment (see Section 10.2)
E 29. Received a live attenuated vaccine within 12 weeks prior to screening (first follow-up visit), or a live attenuated vaccine is planned for the entire trial period, and an inactive vaccine (including RNA vaccines) within 2 weeks prior to screening (first follow-up visit) and during screening (see Table 6 for a list of permitted, restricted, and prohibited drugs, and Section 10.11.4 for a list of prohibited live attenuated vaccines).
E 30. Subjects receiving long-term macrolide (e.g., azithromycin) therapy, unless they have received stable therapy for more than 6 (>6) months prior to screening (first follow-up visit) and experienced at least one exacerbation during this course of treatment. Macrolides are permitted for COPD exacerbations throughout the trial period.
E 31. Subjects receiving phosphodiesterase type 3 (PDE-3) inhibitors (e.g., ensifentrine) or phosphodiesterase type 4 (PDE-4) inhibitors (e.g., roflumislast) therapy, unless they have received stable therapy for more than 6 (>6) months prior to screening (first follow-up visit).
E 32. Subjects receiving xanthine/methylxanthine medications (e.g., theophylline) within 4 weeks prior to screening (first follow-up visit).
E 33. Received anti-IgE therapy (e.g., omalizumab [Xolair®]) within 130 days prior to screening (first follow-up visit), or received any other biologic therapy (including anti-IL-4/interleukin-4 receptor [IL-4R], IL-5/interleukin-5 receptor [IL-5R], IL-13, or TSLP) or systemic immunosuppressant (e.g., methotrexate) for inflammatory or autoimmune diseases (e.g., rheumatoid arthritis, inflammatory bowel disease, primary biliary cirrhosis, systemic lupus erythematosus, or multiple sclerosis) and other conditions (see Table 6).
E 34. The subject is currently receiving COPD control medication that is not locally approved for the treatment of COPD, or is receiving medications or therapies that are prohibited as concomitant therapy (see Table 6).
Previous/Concurrent Clinical Trial Experience
E 35. Currently enrolled or previously involved in another investigational trial, and receiving investigational treatment (e.g., drugs, vaccines, or invasive devices) within the timeframe specified in Table 6.
Diagnostic Assessment
E 36. History of human immunodeficiency virus (HIV) infection, or a positive HIV serological test for HIV type 1 (HIV-1)/HIV type 2 (HIV-2), or a positive HIV deoxyribonucleic acid (DNA) test at screening (first follow-up visit).
E 37. Subjects show any of the following results at screening:
- Positive for Hepatitis B surface antigen (HBsAg) (or inconclusive),
or
- Positive for immunoglobulin M antibody against Hepatitis B core antigen (IgM HBcAb),
- Positive for total Hepatitis B core antibody (HBcAb) as confirmed by a positive result for Hepatitis B virus (HBV) DNA,
or
- Positive for HCV antibody (Ab) as confirmed by a positive result for Hepatitis C virus (HCV) RNA.
For guidance on interpreting hepatitis serological eligibility, please refer to Table 16 in Section 10.7.5.
E 38. Clinically significant laboratory tests at screening (first follow-up visit):
- Alanine transaminase (ALT) or aspartate aminotransferase (AST) above (>) 2 times the upper limit of normal (ULN).
- Serum total bilirubin greater than 1.5 times the ULN (if the subject has Gilbert's syndrome and total bilirubin is greater than 1.5 times the ULN, direct bilirubin less than 1.5 times the ULN is sufficient for inclusion in the trial).
- Heme levels less than 10 times the ULN in men and less than 9 times the ULN in women. - Neutrophil count less than 1500 (<1500)/μL (less than 1000 (<1000)/μL for African Americans).
- Platelet count less than 100,000 (<100,000)/μL.
- Creatinine greater than or equal to 150 (≥150) μmol/L.
Other Exclusion Criteria
E 39. Subjects who withdraw their consent before enrollment/randomization (second follow-up visit), despite prior screening, will be suspended from enrollment/randomization at the trial level.
E 40. Individuals detained in an institution due to regulatory or legal orders; prisoners or subjects lawfully detained.
E 41. Subjects deemed unsuitable for the trial by the trial administrator, regardless of the reason, including medical or clinical conditions, or who may be at risk of non-compliance with trial procedures.
E 42. Inability to comply with trial procedures (e.g., due to language problems, psychological barriers), or inability to read, understand, and complete questionnaires or use electronic diaries without assistance.
E 43. The subject is an employee of the clinical trial center, another person directly involved in conducting the trial, or an immediate family member of such person (see Section 1.61, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, ICH - Good Clinical Practice (GCP) Regulation E6).
E 44. Allergy to any investigational drug or its components, or a history of drug or other allergies, which the trial administrator deems unsuitable for participation.
E 45. Subjects may be unable to participate in this trial due to any country-specific regulations - see Appendix 7 (Section 3.1: Country-Specific/Regional Requirements).
The Estimated Number of Participants
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Taiwan
20 participants
-
Global
942 participants
