A Phase II Study to Evaluate the Efficacy and Safety of SHR-1314 in Lupus Nephritis

Study Overview
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Brief Summary
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To demonstrate the efficacy of SHR-1314 at Week 12 in subjects with proliferation lupus nephritis in terms of improvement of 24h UPCR, compared to placebo. The study will also assess the safety and tolerability of SHR-1314 in the patient population over the study period.

Official Title
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A Multicentre, Randomized, Double-blind, Parallel, Placebo-controlled Phase II Study to Evaluate the Efficacy and Safety of fSHR-1314 in Adult Patients With Lupus Nephritis

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: SHR-1314
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chinese adult pts (18-65yr), Male or Female BMI≥18 kg/m2 and ≤ 35kg/m2 Confirmed diagnosis of LN, renal biopsy report data is within 3-months prior to the date of ICF is first signed 3.1 Biopsy-proven proliferative lupus nephritis Class III or Class IV, either with or without the presence of Class V, using the 2003 ISN/RPS criteria. 3.2 24h UPCR ≥ 1 at screening. 3.3 24h UPR ≥ 1.0 g/d，≤ 3.5 g/d. 3.4 eGFR > 45ml/min/1.73m2. SLEDAI-2K≥8. Exclusion Criteria: Significant medical Problems like myocarditis, pericarditis, severe manifestations of neuropsychiatric SLE (NPSLE) Subjects who have previously treated by both CYC and MMF (or other forms of mycophenolate) With a hHistory of using 60 mg/d prednisolone (or equivalent dose) for more than 3 months prior to Baseline History of inflammatory bowel disease or have other ongoing active autoimmune diseases Required management of acute or chronic infections within the past 8 weeks. At screening, history or symptoms of malignancy of any organ system, treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. History of congestive heart failure (New York Heart Association [NYHA] functional classification ≥III), cerebro-cardiovascular events, or serious bleeding events at screening and / or randomization that in the judgement of the Investigator prevents the subject from participating in the study. History of depression and/or suicidal ideation or any suicidal behavior based on an assessment using the Columbina Suicide Severity Rating Scale (C-SSRS) at screening and baseline . The subjects will be exluded if any answer to question is yes in the questionnaire orare clinically judged by the investigator to be at risk for suicide Receipt of any IL-17/IL-17R targeted therapy within the past year. Those who have participated in any clinical study for any drug or medical device within 3 months before screening. Tested positive for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C. All subjects will be tested for tuberculosis status using IGRA and X-ray test. Subjects with active or latent tuberculosis will be excluded History of severe allergic reaction to contrast agents or biological medicines.Current drug or alcohol abuse or dependence. History of severe allergic reaction to contrast agents or biological medicines.Current drug or alcohol abuse or dependence. Pregnant or nursing..

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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-1314 subcutaneous administration, a multicentre, randomized, double-blind, parallel, placebo-controlled study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment group A<br> | Drug: SHR-1314<br>* SHR-1314 s.c. + Steroids<br>|
| Placebo Comparator: Treatment group B<br> | Drug: Placebo<br>* Placebo s.c. + Steroids<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percentage change of 24 hours UPCR from baseline to Week 12. |  | at 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change of 24 hours UPCR from baseline to Week 24 |  | from baseline to Week 24 | 
| Percentage change of 24 hours UPCR from Week 12 to Week24 |  | from Week 12 to Week24 | 
| Percentage of participants achieving 24h UPCR <0.5 g/g at Week 12 and Week 24 |  | at Week 12 and Week 24 | 
| Percentage of participants achieving renal Complete Response at Week 12 and Week 24 |  | at Week 12 and Week 24 | 
| Percentage of pts achieving renal Partial Response at Week 12 and Week 24 |  | at Week 12 and Week 24 | 
| Change in PGA from baseline to Week 12 and Week 24 |  | from baseline to Week 12 and Week 24 | 
| Change in SLEDAI-2K from baseline to Week 12 and Week 24 |  | from baseline to Week 12 and Week 24 |