A Study to Evaluate the Efficacy and Safety of SHR-1703 in Subjects With Eosinophilic Granulomatosis With Polyangiitis （EGPA）

Study Overview
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Brief Summary
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This study is a phase 2/3 clinical trial to evaluate the efficacy and safety of SHR-1703 in patients with EGPA.

Official Title
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A Single-arm/Randomized, Double-blind, Placebo-controlled, Parallel-group Phase 2/3 Clinical Study to Evaluate the Efficacy and Safety of SHR-1703 for Patients With EGPA

Conditions
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Eosinophilic Granulomatosis With Polyangiitis

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: Male or female subjects age 18 years or older; Diagnosed with EGPA for at least 6 months; History of relapsing or refractory EGPA； Stable dose of oral prednisone of ≥7.5 mg/day (but not >50 mg/day) for at least 4 weeks prior to randomization; If receiving immunosuppressive therapy (excluding cyclophosphamide), the dosage must be stable within 4 weeks prior to randomization and during the study. Exclusion Criteria: Subjects with other eosinophilic-related diseases; Diagnosed with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Life-threatening EGPA within 3 months prior to randomization; Malignancy history within 5 years prior to randomization; Immunodeficiency; Uncontrolled hypertension； Uncontrolled cerebrovascular and cardiovascular disease; parasitic infection within 6 months prior to randomization; Active infectious disease requiring clinical treatment within 4 weeks prior to randomization; Subjects with a dose of oral prednisone of >50 mg/day within 4 weeks prior to randomization; Oral or intravenous cyclophosphamide therapy within 4 weeks prior to randomization; Intravenous or subcutaneous immunoglobulin within 12 weeks prior to randomization; Biological agents or TH2 cytokine inhibitors used within 12 weeks prior to randomization or within 5 half-lives of the drug; Rituximab or alemtuzumab used within 12 months prior to randomization； Surgical plans that might affect the evaluation; Significant laboratory abnormalities； Prolonged QTc interval or other electrocardiogram abnormalities with significant safety risk at screening; History of drug or substance abuse or alcohol abuse within 1 year prior to screening; Subjects participated another clinical study and received active drug within 30 days or 5 half-lives of the drug prior to screening; Subjects is pregnant, lactating, or planning to be 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

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: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: A single-arm/randomized, double-blind, placebo-controlled, parallel-group Phase 2/3 clinical study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group A<br>SHR-1703 | Drug: SHR-1703<br>* SHR-1703 will be administered by Subcutaneous injection in Phase 2 and Phase 3.<br>|
| Placebo Comparator: Treatment group B<br>SHR-1703 Placebo | Drug: SHR-1703 Placebo<br>* SHR-1703 Placebo will be administered by Subcutaneous injection in Phase 3.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in oral glucocorticoid dose (OCS) | Phase 2 | Up to week 12 | 
| The Proportion of subjects in EGPA remission | Phase 3 | week 36 and week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in oral glucocorticoid dose | Effectiveness Indicators (Phase 2) | Up to week 24 | 
| The proportion of subjects with OCS dosage ≤5 mg/d | Effectiveness Indicators (Phase 2) | week 12, week 24 | 
| The proportion of subjects with at least 50% reduction of OCS dosage from baseline | Effectiveness Indicators (Phase 2) | week 12, week 24 | 
| The Proportion of subjects with EGPA remission | Effectiveness Indicators (Phase 2) | week 12, week 24 | 
| The Proportion of subjects with EGPA relapse | Effectiveness Indicators (Phase 2) | week 12, week 24 | 
| The Proportion of subjects with Severe relapse of EGPA | Effectiveness Indicators (Phase 2) | week 12, week 24 | 
| The Proportion of subjects in EULAR remission | Effectiveness Indicators (Phase 2) | week 12 through week 24 | 
| The time to the first relapse of EGPA | Effectiveness Indicators (Phase 2) | Up to week 48 | 
| The time of the first Severe relapse of EGPA | Effectiveness Indicators (Phase 2) | Up to week 48 | 
| Changes from baseline in Pre- and post-Bronchodilator FEV1 | Effectiveness Indicators (Phase 2) | Up to week 48 | 
| Changes from baseline in Pre- and post-Bronchodilator FEV 1% pred | Effectiveness Indicators (Phase 2) | Up to week 48 | 
| Changes from baseline in Pre- and post-Bronchodilator FVC | Effectiveness Indicators (Phase 2) | Up to week 48 | 
| Change from baseline in OCS | Effectiveness indicators (Phase 3) | Week 24, Week 48 | 
| The proportion of subjects with OCS dosage ≤5 mg/d | Effectiveness indicators (Phase 3) | week 24, week 48 | 
| The proportion of subjects with at least 50% reduction of OCS dosage from baseline | Effectiveness indicators (Phase 3) | week 24, week 48 | 
| The total accrued duration of remission | Effectiveness indicators (Phase 3) | up to week 48 | 
| The Proportion of subjects with EGPA relapse | Effectiveness indicators (Phase 3) | week 24, week 48 | 
| The Proportion of subjects with Severe relapse of EGPA | Effectiveness indicators (Phase 3) | week 24, week 48 | 
| The time to the first relapse of EGPA | Effectiveness indicators (Phase 3) | Up to week 48 | 
| The time of the first Severe relapse occurred of EGPA | Effectiveness indicators (Phase 3) | Up to week 48 | 
| The Proportion of subjects in EGPA remission | Effectiveness indicators (Phase 3) | week 24 through week 48 | 
| Changes from baseline in Pre- and post-Bronchodilator FEV1 | Effectiveness indicators (Phase 3) | Up to week 48 | 
| Changes from baseline in Pre- and post-Bronchodilator FEV 1% pred | Effectiveness indicators (Phase 3) | Up to week 48 | 
| Changes from baseline in Pre- and post-Bronchodilator FVC | Effectiveness indicators (Phase 3) | Up to week 48 |