A Study of CM310 in Subjects With Moderate to Severe Asthma

Study Overview
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Brief Summary
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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 CM310 in subjects with moderate to severe asthma. The study consists of three periods, including an up to 4-week screening period, a 24-week randomized treatment period, and a 8-week safety follow-up period.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Study to Evaluate the Efficacy and Safety of CM310 Recombinant Humanized Monoclonal Antibody Injection in Subjects With Moderate to Severe Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: CM310
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects are able to understand the nature of the study and voluntarily sign the ICF. Diagnosed with asthma according to the 2021 version of the GINA guidelines for at least 1 year. Pre-bronchodilator FEV1 measurement ≤ 80% of predicted normal value. Subjects must have experienced a severe asthma exacerbation within 12 months prior to screening, and have not experienced a severe asthma exacerbation within 1 month prior to screening. Exclusion Criteria: Women of childbearing potential have a positive pregnancy test result during the screening period; women who are pregnant or lactating. Received biologics with the same therapeutic purpose within 6 months prior to screening, such as similar IL-4Rα antagonist, IL-5/5R, anti-IgE monoclonal antibody (mAb). Diagnosed with chronic obstructive pulmonary disease (COPD) or other lung disorders that may compromise lung function (including but not limited to idiopathic pulmonary fibrosis, allergic granulomatous angiitis, bronchopulmonary aspergillosis allergic, pulmonary tuberculosis, etc.).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CM310 300mg Q2W<br>CM310 is injected subcutaneously (SC) with a loading dose of 600 mg at the first dose, and then 300 mg each time, once every 2 weeks (Q2W) for a total of 12 doses. | Drug: CM310<br>* CM310 Recombinant Humanized Monoclonal Antibody Injection<br>|
| Experimental: CM310 150mg Q2W<br>CM310 is injected subcutaneously (SC) with a loading dose of 300 mg at the first dose, and then 150 mg each time, once every 2 weeks (Q2W) for a total of 12 doses. | Drug: CM310<br>* CM310 Recombinant Humanized Monoclonal Antibody Injection<br>|
| Placebo Comparator: Placebo<br>Subcutaneous injection (SC), once every 2 weeks (Q2W) for a total of 12 doses. | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in pre-bronchodilator FEV1 (forced expiratory volume in 1 second) at 12 weeks. | Absolute change from baseline in pre-bronchodilator FEV1 in each dose group at 12 weeks of CM310 treatment compared with placebo. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in pre-bronchodilator FEV1 at each evaluation time point. | Absolute change from baseline in pre-bronchodilator FEV1 at each evaluation time point. | 24 weeks | 
| Percent change from baseline in pre-bronchodilator FEV1 at each evaluation time point. | Percent change from baseline in pre-bronchodilator FEV1 at each evaluation time point. | 24 weeks | 
| Annualized rate of subjects experiencing severe asthma exacerbations. | Annualized rate of subjects experiencing severe asthma exacerbations during the 24-week randomized treatment period. | 24 weeks | 
| Time to the first onset of the severe asthma exacerbation event. | Time from baseline to the first onset of the severe asthma exacerbation event. | 24 weeks | 
| Annualized rate of subjects experiencing the event of loss of asthma control (LOAC). | Annualized rate of subjects experiencing the event of loss of asthma control (LOAC) during the 24-week randomized treatment period. | 24 weeks | 
| Time to the onset of the first event of LOAC. | Time from baseline to the onset of the first event of LOAC. | 24 weeks | 
| FEV1 percentage of predicted value (FEV1% Pred) | FEV1 percentage of predicted value (FEV1% Pred) | 32 weeks | 
| Peak diurnal and nocturnal expiratory flow (PEF) | Peak diurnal and nocturnal expiratory flow (PEF) | 32 weeks | 
| Forced vital capacity (FVC) | Forced vital capacity (FVC) | 32 weeks | 
| Maximal mid-expiratory flow (MMEF) | Maximal mid-expiratory flow (MMEF) | 32 weeks | 
| Change from baseline of FEV1 after the use of bronchodilator. | Change from baseline of FEV1 after the use of bronchodilator. | 32 weeks | 
| Change from baseline in the Asthma Control Questionnaire-5 (ACQ-5) score at each evaluation time point. | The ACQ-5 is a questionnaire used to evaluate the degree of asthma control. Each question is scored from 0 to 6 (on a 7-point scale) according to its severity. The higher the score, the less satisfactory symptom control is. | 32 weeks | 
| Change from baseline in asthma symptom score at each evaluation time point. | Patients will record total symptom scores in morning（a 0-4 scale, with 0=no symptoms, 4=inability to fall asleep at night due to symptoms) and afternoon (a 0-5 scale, with 0=no symptoms, 5=severe symptoms, unable to work or perform daily activities). | 32 weeks | 
| Incidence of Adverse events (AEs) | Incidence of AEs, including any abnormal physical examinations, abnormal vital signs, abnormal ECG, and abnormal lab testing. | 32 weeks | 
| Trough concentration at steady-state of CM310 | To evaluate the trough concentration at steady-state of CM310 for each dose group. Population pharmacokinetic analysis is performed using a nonlinear mixed-effects model. | 32 weeks | 
| Human thymus and activation-regulated chemokine (TARC) | Change from baseline in TARC at each evaluation time point for each dose group. | 32 weeks | 
| Fractional exhaled nitric oxide (FeNO). | Change from baseline in FeNO at each evaluation time point for each dose group. | 32 weeks | 
| Total IgE (immunoglobulin E) | Change from baseline in total IgE at each evaluation time point for each dose group. | 32 weeks | 
| Anti-drug antibodies (ADAs) and neutralizing antibodies (Nabs). | Incidence of anti-drug antibodies (ADAs) and neutralizing antibodies (Nabs) (if applicable). | 32 weeks |