A Randomized, Double-Blind, Placebo-Controlled Clinical Study to Evaluate the Efficacy and Safety of CM310 Recombinant Humanized Monoclonal Antibody Injection in Subjects With Moderate to Severe Chronic Obstructive Pulmonary Disease（COPD）
Overview
- Phase
- Phase 2
- Intervention
- CM310
- Conditions
- Chronic Obstructive Pulmonary Disease
- Sponsor
- CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
- Enrollment
- 884
- Primary Endpoint
- Annualized Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Acute Exacerbations
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
Brief 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.
Detailed Description
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. During the first part, patients who meet eligibility criteria will be randomized 1:1:1 to receive either CM310 300 mg, CM310 150mg or matched placebo subcutaneously every two weeks (Q2W) for a total of 26 times at the double-blind treatment period. An interim analysis will be performed and an optimal dose will be recommended. During the second part, patients will be randomized 1:1 to receive either CM310 optimal dose or matched placebo subcutaneously at the double-blind treatment period.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Have the ability to understand the nature of the study and voluntarily sign the informed consent form.
- •Age ≥40 and ≤85 years old, male or female, at the time of signing the informed consent.
- •The patient has been diagnosed with COPD for at least 1 year, and meet the following criteria at screening.
- •Moderate to severe COPD (post-bronchodilator FEV1/FVC ratio \<0.70 and post-bronchodilator FEV1 % predicted \>30% and ≤70%) at screening.
- •Modified Medical Research Council (mMRC) Dyspnea Scale grade ≥
- •Signs and symptoms (chronic productive cough) of chronic bronchitis for at least 3 months in the year up to screening and in the absence of other known causes of chronic cough.
- •Documented history of high exacerbation risk defined as exacerbation history of ≥2 moderate or ≥1 severe AECOPD within the year prior to screening. At least one exacerbation should have occurred while the patient was taking inhaled corticosteroid (ICS)/long acting beta agonist (LABA)/long acting muscarinic antagonist (LAMA) (or LABA/LAMA if ICS is contraindicated). Moderate acute exacerbation of COPD (AECOPD) aredefined as exacerbations that require either systemic corticosteroids (intramuscular, intravenous, or oral) and/or antibiotics. One of the two required moderate exacerbations has to require the use of systemic corticosteroids. Severe AECOPD are defined as exacerbations requiring hospitalization or observation \>24 hours in emergency department/urgent care facility.
- •Background triple therapy (ICS + LABA + LAMA) for 3 months prior to screening with a stable dose of medication for ≥1 month prior to screening; Double therapy (LABA + LAMA) allowed if ICS is contraindicated.
- •Evidence of Type 2 inflammation: Patients with blood eosinophils ≥0.3×10\^9 /L at Visit
- •Body mass index (BMI) ≥16 kg/m\^2
Exclusion Criteria
- •A current diagnosis of asthma or history of asthma according to the Global Initiative for Asthma (GINA) guidelines or other accepted guidelines（asthma alone or asthma as the primary diagnosis, including but not limited to asthma with COPD）.
- •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.
- •Subjects with other conditions that could lead to elevated eosinophils such as hypereosinophilic syndromes, eosinophilic granulomatosis with polyangiitis (EGPA), eosinophilic esophagitis or other disease(e.g., active parasitic infection (helminthes) which has not been treated with, or has failed to respond to standard of care therapy.)
- •Heart failure NYHA Class IV, uncontrolled Cor pulmonale as judged by the Investigator or with evidence of right cardiac failure.
- •Treatment with oxygen of more than 15 hours per day or hypercapnia requiring BiPAP, in the opinion of the investigator,
- •Acute moderate or severe exacerbation of COPD (AECOPD, as defined above in Inclusion Criteria) from 4 weeks before signing consent to the time of randomization.
- •Acute infection requiring systemic anti-infective therapy from 4 weeks before signing consent to the time of randomization.
- •History of or planned pneumonectomy or lung volume reduction surgery for COPD. 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).
- •Diagnosis of α-1 anti-trypsin deficiency.
- •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.
Arms & Interventions
CM310 300mg Q2W
CM310 is injected subcutaneously (SC) 300 mg each time, once every 2 weeks (Q2W) for a total of 26 doses.
Intervention: CM310
CM310 150mg Q2W
CM310 is injected subcutaneously (SC) 150 mg each time, once every 2 weeks (Q2W) for a total of 26 doses.
Intervention: CM310
Placebo
Subcutaneous injection (SC), once every 2 weeks (Q2W) for a total of 26 doses.
Intervention: Placebo
Outcomes
Primary Outcomes
Annualized Rate of Moderate or Severe Chronic Obstructive Pulmonary Disease (COPD) Acute Exacerbations
Time Frame: Baseline (Day 1) to 52 weeks
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.
Secondary Outcomes
- Time to First Moderate or Severe Acute Exacerbation of COPD (AECOPD)(Baseline (Day 1) to 52 weeks)
- Percentage of Participants With SGRQ Improvement >=4 Points from baseline at Week 52(Baseline (Day 1) to 52 weeks)
- Change from baseline in pre-bronchodilator FEV1 at week 52(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(Baseline (Day 1) to week 2,4,8,16,20,24,28,36,44,48)
- 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(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(Baseline (Day 1) to 52 weeks)
- Potentially clinically significant laboratory abnormalities in hematology, biochemistry and urinalysis(Baseline (Day 1) to 60 weeks)
- Annualized Rate of Severe Acute Exacerbations of COPD(Baseline (Day 1) to 52 weeks)
- Change from baseline in post-bronchodilator FEV1 at week 2,4,8,12,24,36,52(Baseline (Day 1) to week 2,4,8,12,24,36,52weeks)
- Change from baseline in Evaluating Respiratory Symptoms (E-RS) total score at each evaluation time point(Baseline (Day 1) to week 2,4,8,12,24,36,44,52weeks)
- Neutralizing antibodies(immunogenicity parameters)(Baseline (Day 1) to 60 weeks)
- Change from baseline in pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at week 12(Baseline (Day 1) to 12 weeks)
- Change from baseline in COPD assessment test (CAT) Total Score at each evaluation time point(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(Baseline (Day 1) to 52 weeks)
- Trough concentration at steady-state of CM310 (Pharmacokinetic parameters）(Baseline (Day 1) to 60 weeks)
- Anti-drug antibodies(immunogenicity parameters)(Baseline (Day 1) to 60 weeks)
- Percentage of Participants With E-RS Improvement >=2 Points from baseline at Week 52(Baseline (Day 1) to 52 weeks)
- Incidence of Adverse events (AEs)/treatment-emergent adverse events (TEAEs)(Baseline (Day 1) to 60 weeks)
- Total IgE(Pharmacodynamic biomarkers)(Baseline (Day 1) to 60 weeks)
- Fractional exhaled nitric oxide (Pharmacodynamic biomarkers)(Baseline (Day 1) to 60 weeks)