Chronic Obstructive Pulmonary Disease
Conditions
Brief summary
This study is a multi-center, randomized, double-blind, placebo-controlled Phase II clinical study to evaluate the efficacy, safety, PK characteristics, PD effects and immunogenicity of CM326 in subjects with moderate to Severe Chronic Obstructive Pulmonary Disease. The study consists of a screening period of up to 4 weeks, a randomized treatment period of 24 to 52 weeks, and a 12-week safety follow-up period.
Interventions
DRUGCM326 dose 1
subcutaneous injection
DRUGCM326 dose 2
subcutaneous injection
OTHERPlacebo
subcutaneous injection
Sponsors
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Understand the study and voluntarily sign the informed consent form. 2. Age ≥40 and ≤85 years old, male or female, at the time of signing the informed consent. 3. weight ≥40 kg. 4. Diagnosed with COPD for at least 12 months. 5. Post-bronchodilator FEV1/FVC ratio \<0.70 and post-bronchodilator FEV1 % predicted ≥20% and \<80%. 6. Background therapy for 3 months prior to screening with a stable dose of medication for ≥1 month prior to screening. 7. Exacerbation history of ≥2 moderate or ≥1 severe AECOPD within the year prior to screening. 8. COPD assessment test (CAT) Total Score ≥10. 9. Blood eosinophils ≥0.15×10\^9 /L at screening. 10. Current smoking or a history of smoking ≥ 10 pack-years, or exposure to biomass smoke (including but not limited to biomass fuel, secondhand smoke, and the like) for ≥ 10 years. 11. Voluntarily use highly effective contraception from the time of signing the informed consent form until 3 months after the last dose.
Exclusion criteria
1. A current diagnosis of asthma or history of asthma according to the Global Initiative for Asthma (GINA) guidelines（asthma alone or asthma as the primary diagnosis, including but not limited to asthma with COPD） 2. Subjects with significant pulmonary disease other than COPD (e.g., sarcoidosis, interstitial lung disease, primary pulmonary hypertension, bronchiectasis, Churg-Strauss Syndrome, active tuberculosis or non-tuberculous mycobacterial infection, etc.), in the opinion of the investigator. Or other conditions that could lead to elevated eosinophils. 3. The presence of any severe and/or uncontrolled medical condition that in the judgment of the investigator would affect the evaluation of the drug, including but not limited to: severe neurological disease (eg, epilepsy, dementia, etc), history of severe mental disorder, major cardiovascular disease, diabetes mellitus poorly controlled by intensive treatment, QTcF interval prolongation（male \>450 msec, female \>470 msec）, or persistent arrhythmia. 4. History of malignancy. 5. Previous history of known or suspected immunosuppression; Or the presence of unusual frequent, recurrent, or prolonged infections, per investigator's judgment. 6. Prior autoimmune disease or inflammatory treatment with biologic agents/systemic immunosuppressive agents within 8 weeks or 5 half-lives (whichever is longer) prior to informed consent. 7. Heart failure NYHA Class IV, uncontrolled Cor pulmonale as judged by the investigator or with evidence of right cardiac failure. 8. Myocardial infarction, unstable angina, or stroke occurring within 6 months prior to signing the informed consent form (ICF). 9. Parasitic infection diagnosed within 24 weeks prior to signing the informed consent form (ICF), which has not received standard treatment or is refractory to standard treatment. 10. Acute moderate or severe exacerbation of COPD from 4 weeks before signing consent to the time of randomization. 11. Acute infection requiring systemic anti-infective therapy from 4 weeks before signing consent to the time of randomization. 12. Major surgery within 8 weeks prior to consent or planned surgery requiring general anesthesia or hospitalization for \> 1 day during the study period. 13. History of or planned pneumonectomy or lung volume reduction surgery for COPD 12 months prior to screening. 14. As judged by the investigator, long-term daily oxygen therapy for more than 15 hours per day due to medical necessity, or concurrent hypercapnia requiring the use of bilevel positive airway pressure (BiPAP) non-invasive ventilation. 15. Patients who are participating in the acute phase of a pulmonary rehabilitation program, ie, who start rehabilitation \<4 weeks prior to screening (Note: patients in the maintenance phase of a rehabilitation program could be included). 16. Patients who are treated with systemic corticosteroids (topical, ophthalmic, or intranasal corticosteroids are excluded) from 4 weeks before signing the informed consent to the date of randomization. Except for short-term (≤7 days) use of systemic glucocorticoids to prevent or treat non-autoimmune allergic diseases. 17. Use of macrolide antibiotics (eg, azithromycin) unless stable \>3 months prior to screening visit and maintain the treatment during the planned study period. 18. Treatment with a PDE-4 inhibitor (roflumilast) (unless on stable treatment for ≥ 3 months with a plan to maintain stable treatment throughout the study period).。 19. Anti-immunoglobulin E (IgE) therapy (omalizumab) within 130 days before consent or any other biologic therapy (including other anti-IL4R mAb, anti-IL5 mAb, anti-IL5R mAb, anti TSLP mAb, anti-IL33 mAb, anti-ST2 mAb) within 3 months or 5 half-lives before signing consent, whichever is longer. 20. Have been enrolled in a clinical trial of any drug or medical device within 3 months before signing informed consent, or are within the follow-up period of a clinical study or the five half-lives of the trial drug (whichever is longer) before signing informed consent. 21. Received immune globulin or blood products within 30 days before informed consent. 22. Receipt of traditional Chinese medicines (TCMs), ethnic medicines, or natural medicines approved by the National Medical Products Administration (NMPA) for the indication of COPD treatment within 4 weeks prior to randomization. 23. Receipt of live or attenuated vaccine within 3 months before consent signing or during the planned study period. 24. Non-negative HIV serological test result at screening, or Treponema pallidum infection requiring treatment. 25. Subjects infected with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) must meet the following laboratory criteria during the screening period: a. HBsAg positive b. HBsAg negative , HBcAb positive, HBV DNA exceed the lower limit of quantitation (LLOQ) or 1000 copies/mL c. HCV antibody positive, HCV RNA exceed the LLOQ. 26. At screening, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 × upper limit of normal (ULN), or serum creatinine (Cr) \> 1.5 × ULN or serum creatinine \> 1.5 × ULN. 27. Females with a positive pregnancy test, pregnant females, or lactating females. 28. Allergy or intolerance to components of CM326 injection or placebo or history of severe drug allergy or anaphylactic shock. 29. History of drug abuse within 5 years before signing informed consent. 30. \<70% compliance with usual COPD controller therapy in subjects during the screening phase. 31. The investigator considers that there are any conditions that may prevent the subject from completing the study .
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Acute Exacerbations | week 24-52 | Annualized rate of moderate or severe acute exacerbation of COPD (AECOPD) over the placebo-controlled treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1) at each evaluation time point | week 16-24 | FEV1 is the volume of air exhaled in the first second of a forced expiration as measured by spirometer. Change from baseline in FEV1 taken before bronchodilator use will be reported. |
| Change from baseline in post-bronchodilator forced expiratory volume in 1 second (FEV1) at each evaluation time point | week 24-52 | FEV1 is the volume of air exhaled in the first second of a forced expiration as measured by spirometer. Change from baseline in FEV1 taken after bronchodilator use will be reported. |
| Change from baseline in Pre-bronchodilator Forced vital capacity (FVC) at each evaluation time point | week 24-52 | Change from baseline in forced vital capacity taken before bronchodilator use will be reported. FVC is measured by spirometer. |
| Change from baseline in forced expiratory flow (FEF) at 25%-75% at each evaluation time point | week 24-52 | FEF is measured by spirometer. |
| Time to the first onset of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Acute Exacerbations | week 24-52 | Time to first moderate or severe AECOPD over the placebo-controlled treatment period. |
| Time to the first onset of Severe Chronic Obstructive Pulmonary Disease (COPD) Acute Exacerbations | week 24-52 | Time to first severe AECOPD over the placebo-controlled treatment period. |
| Annualized Rate of Severe Chronic Obstructive Pulmonary Disease (COPD) Acute Exacerbations | week 24-52 | Annualized rate of severe AECOPD over the placebo-controlled treatment period. |
| Change from baseline in Saint (St.) George's Respiratory Questionnaire (SGRQ) Total Score at each evaluation time point | week 24-52 | The SGRQ is a 50-item questionnaire designed to measure and quantify health status in adult participants with chronic airflow limitation. A global score ranges from 0 to 100. Scores by dimension are calculated for 3 domains: Symptoms, Activity and Impacts (Psycho-social) as well as a total score. A lower score indicates better quality of life. |
| Proportion of participants with an SGRQ Score improvement of ≥4 points from baseline at each evaluation time point. | week 24-52 | Proportion of participants achieving a clinically meaningful improvement from baseline in SGRQ total score (4-point score decrease) will be reported. |
| Change from baseline in COPD assessment test (CAT) Total Score at each evaluation time point | week 24-52 | CAT is an 8-item PRO that measures the impact of COPD on the health status of patients with COPD. The CAT has a scoring range of 0-40 with higher scores indicative of greater COPD impact on health status. |
| Proportion of participants with an CAT Score improvement of ≥2 points from baseline at each evaluation time point | week 24-52 | Proportion of participants achieving a clinically meaningful improvement from baseline in CAT total score (2-point score decrease) will be reported. |
| Change from baseline in Evaluating Respiratory Symptoms (E-RS) total score at each evaluation time point | week 24-52 | The E-RS: COPD is administered as a part of the 14-item EXACT questionnaire and is completed on a daily basis. The 11-item E-RS:COPD assesses severity of respiratory symptoms overall and severity of individual symptoms such as breathlessness, cough and sputum, and chest symptoms The total score of E-RS:COPD ranges from 0 to 40, with higher values indicating more severe respiratory symptoms. |
| Proportion of participants with an E-RS Score improvement of ≥2 points from baseline at each evaluation time point | week 24-52 | Proportion of participants achieving a clinically meaningful improvement from baseline in E-RS total score (2-point score decrease) will be reported. |
| Incidence of Adverse events (AEs)/treatment-emergent adverse events (TEAEs) in | week 64 | The severity of adverse events is recorded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 6.0. The incidence of participants with adverse events (AE) will be calculated. |
| Blood drug concentration Pharmacokinetic profile of CM326 | week 64 | — |
| Pharmacodynamics profile of CM326 Change from baseline fractional exhaled nitric oxide (FeNO) | week 64 | Evaluate the changes from baseline in FeNO at each visit point. |
| Change from baseline in peripheral blood eosinophil | week 64 | Evaluate the changes from baseline in blood eosinophil count at each visit point. |
| Change from baseline in total serum IgE | week 64 | Evaluate the changes from baseline in total serum IgE at each visit point. |
| Change from baseline in interleukin-5 | week 64 | Evaluate the changes from baseline in blood serum IgE at each visit point |
| Incidence of anti-drug antibodies (ADAs) | week 64 | — |
Countries
China
Contacts
CONTACTClinical Trials Information Group officer
Outcome results
None listed