A Study to Evaluate the Pharmacodynamic, Efficacy and Safety of SHR-1703 in Asthma Patients With Eosinophil Phenotype

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the Pharmacodynamic, Efficacy and Safety of SHR-1703 in Asthma Patients with Eosinophil Phenotype.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase II Clinical Study to Evaluate the Pharmacodynamic, Efficacy and Safety of Multiple Subcutaneous Injections of SHR-1703 in Asthma Patients With Eosinophil Phenotype

Conditions
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Asthma With Eosinophilic Phenotype

Intervention / Treatment
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* Drug: SHR-1703
* Drug: SHR-1703 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 to 75years (inclusive). Weight ≥40 kg. History of asthma≥ 1 year. Documented treatment with Medium or high daily dose inhaled corticosteroid with additional controller medication within the 3 months prior to randomization. Previously confirmed history of one or more asthma exacerbations within 1 year prior to randomization. Blood eosinophils of ≥150 cells/µL at screening and baseline. Pre-Bronchodilator FEV1% pred≥40% and<80% at screening and baseline. Asthma Control Questionnaire-6 score≥1.5. Use highly effective contraceptive measures. Willing to sign the informed consent form to participate in this study. Exclusion Criteria: Subjects with Clinically significant pulmonary diseases； Subjects with other diseases that could lead to elevated eosinophils； Subjects with Immunodeficiency； Poorly controlled hypertension; Subjects with severe cerebrovascular disease; Subjects with infection history requiring clinical intervention； Subjects with parasitic infection； Diagnosed Malignant tumor within 5 years prior to randomization; Used non-selective β-blockers within 1 week prior to randomization; Used either 5-lipoxygenase inhibitor or Phosphodiesterase-4 inhibitor within 1 week prior to randomization; Blood donation or massive blood loss, or transfusion of blood products or immunoglobulins within 4 weeks prior to randomization; Live attenuated vaccine inoculated within 4 weeks before randomization; Allergen Immunotherapy within 8 weeks prior to randomization； Used systemic immunosuppressants or immunomodulators, or biologics or Th2 cytokine inhibitors within 12 weeks prior to randomization or within 5 half-lives of the drug; Bronchial thermoplasty within 1 year prior to randomization； Subjects have planned Surgery or other medical procedures that may affect evaluation during the study period; Subjects with significant laboratory abnormality at screening； Subjects have prolonged QTc interval or other electrocardiogram abnormality with significant safety risk at screening; Current smokers or ex-smokers who have given up smoking for <6 months ，or positive smoke test, and/or have a smoking pack history of > 10 pack years; History of drug or substance abuse or alcohol abuse within 1 year prior to screening; Subjects participated another clinical studies and received active drug within 30 days or 5 half-lives prior to screening; Subjects is pregnant, lactating,or planning to become pregnant; Subjects have a known history of hypersensitivity or intolerance to anti-IL-5 mabs or other biological agents; Other conditions unsuitable for participation in the study per investigator judgement.

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
Interventional Model Description: Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase II Clinical Study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects receiving SHR-1703 dose 1<br> | Drug: SHR-1703<br>* SHR-1703 will be administered by SC injection.<br>Drug: SHR-1703 Placebo<br>* Matching Placebo will be administered by the SC route.<br>|
| Experimental: Subjects receiving SHR-1703 dose 2<br> | Drug: SHR-1703<br>* SHR-1703 will be administered by SC injection.<br>|
| Experimental: Subjects receiving SHR-1703 dose 3<br> | Drug: SHR-1703<br>* SHR-1703 will be administered by SC injection.<br>Drug: SHR-1703 Placebo<br>* Matching Placebo will be administered by the SC route.<br>|
| Placebo Comparator: Placebo<br> | Drug: SHR-1703 Placebo<br>* Matching Placebo will be administered by the SC route.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in Blood Eosinophils |  | Up to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in Pre- and post-Bronchodilator FEV1 |  | Up to Week 52 | 
| Changes from baseline in Pre- and post-Bronchodilator FEV 1% pred |  | Up to Week 52 | 
| Changes from baseline in Pre- and post-Bronchodilator FVC |  | Up to Week 52 | 
| Changes from baseline in Pre- and post-Bronchodilator PEF |  | Up to Week 52 | 
| Changes from baseline in n fractional exhaled nitric oxide (FeNO) |  | Up to Week 52 | 
| Changes from baseline in Asthma Control Questionnaire-6(ACQ-6) |  | Up to Week 52 | 
| Changes from baseline in Standardized Asthma Quality of Life Questionnaire (AQLQ) |  | Up to Week 52 | 
| Frequency of use of asthma relievers |  | Up to Week 24 | 
| Frequency of exacerbations of asthma |  | Up to Week 24 | 
| Frequency of severe exacerbations of asthma |  | Up to Week 24 | 
| Time to first exacerbation of asthma |  | Up to Week 24 | 
| Time to first severe exacerbation of asthma |  | Up to Week 24 |