A Trial of SHR-1905 in Subjects With Severe Uncontrolled Asthma

Study Overview
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Brief Summary
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This study is a phase 2 study of SHR-1905 in subjects with severe uncontrolled asthma. The purpose of the study is to evaluate efficacy and safety of SHR-1905 in subjects with severe uncontrolled asthma.

Official Title
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A Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase 2 Study to Evaluate the Efficacy and Safety of SHR-1905 in Subjects With Severe Uncontrolled Asthma.

Conditions
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Asthma

Intervention / Treatment
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* Drug: SHR-1905
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged between 18 and 75 years (inclusive) Weight ≥ 40 kg Meet the diagnostic criteria for asthma and have a medical history of at least 1 year Treatment with a total daily dose of either medium or high dose inhaled glucocorticoids (ICS) for at least 6 months before screening, with a stable use for 3 months before randomization At least one additional maintenance asthma controller with stable use for at least 3 months before randomization No birth plan and must agree to take effective contraceptive methods Sign informed consent form voluntarily for the trial Exclusion Criteria: Any clinically important pulmonary disease Any disease other than asthma that may affect lung function Any disease other than asthma related to elevation of eosinophils Any immunodeficiency disease Any clinically important serious cardiovascular diseases unstable or uncontrolled Uncontrolled Hypertension Uncontrolled Diabetes Mellitus Any clinically important infections within 4 weeks before randomization Any major surgery within 3 months before randomized, or any surgical plan during the study, or any treatment that the investigator think affect the evaluation of the subjects Any parasitic infections within 6 months before randomization Malignancy diagnosed within 5 years before randomization Abnormal laboratory tests during screening and baseline Positive infectious disease test Prolonged QTc interval or other clinical significant abnormal findings in ECG at screening that may causesafety risk to the subject Current smoker or smoking cessation for less than 6 months at screening, and/or positive nicotine test during screening，or smoking history ≥10 pack- years Positive alcohol breath test and positive urine drug test at screening Allergy history to any biological or other agent that investigator think the subject should not participate in the study Subjects who are pregnant or breastfeeding, or plan to become pregnant during the study Participated in other clinical trials and used investigational drugs containing active ingredients within 4 weeks or 5 half-lives before screening Any other circumstance judged by the investigatorinappropriate for participating in the clinical trial

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: SHR-1905 compared with placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort A<br>dose 1 | Drug: SHR-1905<br>* subcutaneous<br>|
| Experimental: Cohort B<br>dose 2 | Drug: SHR-1905<br>* subcutaneous<br>|
| Experimental: Cohort C<br>dose 3 | Drug: SHR-1905<br>* subcutaneous<br>|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* subcutaneous ,placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy：Annual asthma exacerbation rate (AAER) |  | From randomisation to 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in forced expiratory volume in one second (FEV1) |  | From randomisation to 72 weeks | 
| Changes from baseline in forced vital capacity (FVC) |  | From randomisation to 72 weeks | 
| Changes from baseline in peak expiratory flow (PEF) pre/post-bronchodilator (pre/ post-BD) |  | From randomisation to 72 weeks | 
| Changes of fractional exhaled nitric oxide (FeNO) compared with baseline at each evaluation time |  | Baseline to72 weeks | 
| Changes of blood eosinophils (EOS) compared with baseline at each evaluation time |  | Baseline to72 weeks | 
| Changes of serum immunoglobulin E (IgE) compared with baseline at each evaluation time |  | Baseline to72 weeks | 
| Changes from baseline in Asthma Control questionnaire (ACQ-6) scores |  | Baseline to 72 weeks | 
| Changes from baseline in Asthmatic Quality of Life Questionnaire (AQLQ) scores |  | Baseline to 72 weeks | 
| AAER associated with hospitalization at 48 weeks |  | From randomisation to 48 weeks | 
| Changes from baseline in weekly mean daily Asthma Symptom Diary scores |  | Baseline to 72 weeks | 
| The proportion of subjects with acute exacerbations of asthma |  | Baseline to 72 weeks | 
| Changes from baseline in weekly reliever use |  | Baseline to 72 weeks | 
| Changes from baseline in weekly mean morning and evening peak expiratory flow (PEF) |  | Baseline to 72 weeks | 
| Changes from baseline in weekly mean number of night time awakenings |  | Baseline to 72 weeks | 
| Time to the first acute asthma exacerbation |  | Baseline to 72 weeks | 
| Changes of the Sino-Nasal Outcome Test-22-item (SNOT-22) score in patients with nasal polyps at each evaluation time |  | Baseline to 72 weeks | 
| The proportion of subjects with composite endpoint for asthma (CompEx) |  | Baseline to72 weeks | 
| Safety: Adverse events |  | Baseline to 72 weeks | 
| Safety: Serious adverse events |  | Baseline to 72 weeks | 
| Pharmacokinetics (PK): Serum concentration of SHR-1905 |  | 72 weeks | 
| Immunogenicity: The incidence of anti-drug antibody (ADA) |  | 72 weeks | 
| Immunogenicity: The timing of anti-drug antibody (ADA) |  | 72 weeks | 
| Immunogenicity: The duration of anti-drug antibody (ADA) |  | 72 weeks | 
| Immunogenicity: The titer of anti-drug antibody (ADA) |  | 72 weeks |