A Study to Evaluate the Efficacy and Safety of SHR0302 in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This study is to evaluate the efficacy and safety of different doses of JAK1 inhibitor SHR0302 in subjects with moderate to severe active rheumatoid arthritis who had inadequate response to conventional synthetic DMARDs.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled Phase 3 Clinical Study to Evaluate the Efficacy and Safety of SHR0302 in Moderate to Severe Active Rheumatoid Arthritis Subjects With Inadequate Response to csDMARDs.

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: SHR0302
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide signed informed consent. RA diagnosis consistent with the 2010 ACR/EULAR criteria; Moderate to severe RA defined by 6 or more tender joints, 6 or more swollen joints (68- or 66-joint count), and an ESR of 28 mm/h or greater or a CRP level greater than 5mg/L. Subjects were required to have an inadequate response to treatment with csDMARDs before baseline. If subjects are taking permitted csDMARDs or low-dose corticosteroid orally at baseline , the stable doses should have lasted for more than 4 weeks already. BMI ≥18 kg/m2 Exclusion Criteria: Pregnant women or refuse to receive contraception during the study. Lab abnormality within 4 weeks of randomization as follows: WBC count <3.0×10^9/L；neutrophil count<1.5×10^9/L;hemoglobin level<90.0 g/L ; platelet count <100×10^9/L; AST or ALT levels greater than the upper limit of normal; HBsAg or HCV or HIV antibody positivity. History of another autoimmune rheumatic disease ; history of cancer or infection including tuberculosis and hepatitis; history of important cardiovascular events or thrombotic diseases. Previous treatment with JAK inhibitor or cytotoxic drugs; bDMARDs within 6 months of randomization; other strong immunosuppressants within 3 months of randomization.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* The placebo group will take drugs orally for 24 weeks, and then switch to SHR0302 dose1 for 28 weeks, in the meanwhile, SHR0302 dose1 group and SHR0302 dose2 group will continue taking drugs for the whole 52 weeks.<br>|
| Experimental: SHR0302 dose1<br> | Drug: SHR0302<br>* The placebo group will take drugs orally for 24 weeks, and then switch to SHR0302 dose1 for 28 weeks, in the meanwhile, SHR0302 dose1 group and SHR0302 dose2 group will continue taking drugs for the whole 52 weeks.<br>|
| Experimental: SHR0302 dose2<br> | Drug: SHR0302<br>* The placebo group will take drugs orally for 24 weeks, and then switch to SHR0302 dose1 for 28 weeks, in the meanwhile, SHR0302 dose1 group and SHR0302 dose2 group will continue taking drugs for the whole 52 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR20 response rate at week 24 | Response rate of 20% improvement in American College of Rheumatology (ACR20) criteria at week 24 | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR20 response rate at week 52 | Response rate of 20% improvement in American College of Rheumatology (ACR20) criteria at week 52 | Week 52 | 
| ACR50 response rate at week 24 and week 52 | Response rate of 50% improvement in American College of Rheumatology (ACR50) criteria at week 24 and week 52 | Week 24 and week 52 | 
| ACR70 response rate at week 24 and week 52 | Response rate of 70% improvement in American College of Rheumatology (ACR70) criteria at week 24 and week 52 | Week 24 and week 52 | 
| Change from baseline in HAQ-DI score at week 24 and week 52 | Change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) score at week 24 and week 52 | Week 24 and week 52 | 
| Change from baseline in SF-36 score at week 24 and week 52 | Change from baseline in the medical outcomes study 36-Item Short-Form Health Survey (SF-36) score at week 24 and week 52 | Week 24 and week 52 | 
| DAS28-CRP <2.6 proportion at week 24 and week 52 | Disease Activity Score for 28-joint counts based on the c-reaction protein (DAS28-CRP) of less than 2.6 | Week 24 and week 52 | 
| DAS28-CRP≤3.2 proportion at week 24 and week 52 | Disease Activity Score for 28-joint counts based on the c-reaction protein (DAS28-CRP) of equal to and less than 3.2 | Week 24 and week 52 |