A Study of CM310 in Subjects With Moderate to Severe Chronic Obstructive Pulmonary Disease
NCT Number: NCT06547333
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2|PHASE3
Conditions: Chronic Obstructive Pulmonary Disease
Interventions: DRUG: CM310|DRUG: Placebo
Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 884
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-09-13
Completion Date: 2032-10-31

Summary:
This study is a multi-center, randomized, double-blind, placebo-controlled Phase Ⅱ/Ⅲ clinical study to evaluate the efficacy, safety, PK characteristics, PD effects and immunogenicity of CM310 in subjects with moderate to severe Chronic Obstructive Pulmonary Disease（COPD）.

The study has two parts. Each part consists of three periods, including an up to 4-week screening period, a 52-week randomized treatment period, and a 8-week safety follow-up period.

Primary Outcome Measures: Annualized Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Acute Exacerbations, Moderate acute exacerbation of COPD (AECOPD) are defined as exacerbations that require either systemic corticosteroids (intramuscular, intravenous, or oral) and/or antibiotics. Severe AECOPD are defined as exacerbations requiring hospitalization or observation \>24 hours in emergency department/urgent care facility. For both moderate and severe events to be counted as separate events, they are separated by at least 14 days. Annualized event rate are the total number of exacerbations that occure during the treatment period divided by the total number of participant-years treated., Baseline (Day 1) to 52 weeks
Secondary Outcome Measures: Time to First Moderate or Severe Acute Exacerbation of COPD (AECOPD), The time to first moderate or severe exacerbation is defined as date of the first event minus randomization date +1. The median time to first severe exacerbation is derived from Cox regression model., Baseline (Day 1) to 52 weeks|Annualized Rate of Severe Acute Exacerbations of COPD, Severe AECOPD are defined as exacerbations requiring hospitalization or observation \>24 hours in emergency department/urgent care facility. For severe events to be counted as separate events, they are separated by at least 14 days. Annualized event rate are the total number of exacerbations that occure during the treatment period divided by the total number of participant-years treated., Baseline (Day 1) to 52 weeks|Change from baseline in pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at week 12, The FEV1 is the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. Spirometry is performed after a wash out period of bronchodilators according to their action duration., Baseline (Day 1) to 12 weeks|Change from baseline in pre-bronchodilator FEV1 at week 52, The FEV1 is the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. Spirometry is performed after a wash out period of bronchodilators according to their action duration., Baseline (Day 1) to 52 weeks|Change from baseline in pre-bronchodilator FEV1 at week 2,4,8,16,20,24,28,36,44,48, The FEV1 is the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. Spirometry is performed after a wash out period of bronchodilators according to their action duration., Baseline (Day 1) to week 2,4,8,16,20,24,28,36,44,48|Change from baseline in post-bronchodilator FEV1 at week 2,4,8,12,24,36,52, The FEV1 is the volume of air exhaled from the lungs in the first second of a forced expiration as measured by spirometer. Post-BD FEV1 refers to the spirometry performed within 15-30 minutes after administration of bronchodilator., Baseline (Day 1) to week 2,4,8,12,24,36,52weeks|Change from baseline in Forced vital capacity（FVC）and forced expiratory flow (FEF) at 25%-75% at week 2,4,8,12,16,24,28,36,44,52, FVC is defined as the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. FEF is the amount of air (in liters) which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FEF 25-75% is defined as the mean FEF between 25% and 75% of the FVC. Spirometry is performed after a wash out period of bronchodilators according to their action duration., Baseline (Day 1) to week 2,4,8,12,16,24,28,36,44,52weeks|Change from baseline in Saint (St.) George's Respiratory Questionnaire (SGRQ) Total Score at week 52, The SGRQ is a 50-item self-administered questionnaire designed to measure and quantify health status in adult participants with chronic airflow limitation and rate on electronic diary. Scores by dimension are calculated for 3 domains: symptoms, activity and impacts (psycho-social) as well as a total score. Global and domain scores range from 0 to 100, with 100 representing the worst possible health status and 0 indicating the best possible health status. Higher score indicates worse health status/heath related quality of life., Baseline (Day 1) to 52 weeks|Percentage of Participants With SGRQ Improvement >=4 Points from baseline at Week 52, A responder is defined as a participant with improvement from baseline in SGRQ total score at Week 52 by \>=4 points. Participants with improvement \<4 points or with missing values are considered as non-responders. The percentage of participants who achieved a clinically meaningful response in SGRQ total score (reduction \[improvement\] by \>=4 points)/responders are reported., Baseline (Day 1) to 52 weeks|Change from baseline in COPD assessment test (CAT) Total Score at each evaluation time point, The COPD Assessment Test is a validated, short and simple patient completed questionnaire to measure the health status of patients with COPD. The CAT is an 8-item questionnaire suitable for completion by all patients diagnosed with COPD. When completing the questionnaire, subjects rate their experience on a 6-point scale, ranging from 0 (no impairment) to 5 (maximum impairment) with a scoring range of 0-40. Higher scores indicate greater disease impact., Baseline (Day 1) to week 2,4,8,12,24,36,44,52weeks|Percentage of Participants With CAT Improvement >=2 Points from baseline at Week 52, A responder is defined as a participant with improvement from baseline in CAT total score at Week 52 by \>=2 points. Participants with improvement \<2 points or with missing values are considered as non-responders. The percentage of participants who achieved a clinically meaningful response in CAT total score (reduction \[improvement\] by \>=2points)/responders are reported., Baseline (Day 1) to 52 weeks|Change from baseline in Evaluating Respiratory Symptoms (E-RS) total score at each evaluation time point, The E-RS in COPD scale is a derivative instrument used to measure the effect of treatment on the severity of respiratory symptoms in stable COPD. E-RS: COPD RS-Total Score is derived based on weekly averages of daily assessed 11 respiratory symptom items contained in the 14-item EXACT questionnaire. The RS-Total score represent overall respiratory symptom severity, ranged from 0 to 40. The higher the score, more severe are the symptoms., Baseline (Day 1) to week 2,4,8,12,24,36,44,52weeks|Percentage of Participants With E-RS Improvement >=2 Points from baseline at Week 52, A responder is defined as a participant with improvement from baseline in E-RS total score at Week 52 by \>=2 points. Participants with improvement \<2 points or with missing values are considered as non-responders. The percentage of participants who achieved a clinically meaningful response in E-RS total score (reduction \[improvement\] by \>=2points)/responders are reported., Baseline (Day 1) to 52 weeks|Incidence of Adverse events (AEs)/treatment-emergent adverse events (TEAEs), An Adverse Event (AE) is defined as any untoward medical occurrence in a participant temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs are defined as AEs that developed or worsened in grade or became serious during TE period which is defined as the period from the time of first dose of study treatment until the last visit in the study., Baseline (Day 1) to 60 weeks|Potentially clinically significant laboratory abnormalities in hematology, biochemistry and urinalysis, Any abnormal laboratory test results (hematology, biochemistry, or urinalysis) including those that worsen from baseline, and felt to be clinically significant in the medical and scientific judgment of the investigator are to be recorded., Baseline (Day 1) to 60 weeks|Trough concentration at steady-state of CM310 (Pharmacokinetic parameters）, To evaluate the trough concentration at steady-state of CM310 for each dose group. Population pharmacokinetic analysis is performed., Baseline (Day 1) to 60 weeks|Total IgE(Pharmacodynamic biomarkers), Change from baseline in total IgE at each evaluation time point for each dose group., Baseline (Day 1) to 60 weeks|Fractional exhaled nitric oxide (Pharmacodynamic biomarkers), FeNO is a demonstrated biomarker of type 2 airway inflammation in respiratory diseases. This assessment is conducted prior to spirometry. Change from baseline in FeNO at each evaluation time point for each dose group is measured., Baseline (Day 1) to 60 weeks|Anti-drug antibodies(immunogenicity parameters), Incidence of anti-drug antibodies (ADAs), Baseline (Day 1) to 60 weeks|Neutralizing antibodies(immunogenicity parameters), Incidence of neutralizing antibodies (Nabs) (if applicable), Baseline (Day 1) to 60 weeks