Study of Recombinant Human B Lymphocyte(RC18) Administered Subcutaneously to Subjects With Systemic Lupus Erythematosus(SLE)

Study Overview
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Brief Summary
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The purpose of this study is to initially access the safety and effectivity of RC18 combined with standard treatment and Placebo combined with standard therapy in subjects with Moderate to severe SLE.

Official Title
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A Phase III, Placebo-Controlled ,Multi-Center, Randomized, Double-Blind, Dose-exploring Trial of RC18,a Recombinant Human B Lymphocyte Stimulating Factor Receptor-Antibody Fusion Protein in Subjects With Systemic Lupus Erythematosus (SLE).

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Biological: Placebo plus standard therapy
* Biological: RC18 160 mg plus standard therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Active SLE disease#and at least according with 4 of the 11 items of the American College of Rheumatology (ACR) criteria 1997. Age & Gender: Male or female between 18 and 65 years of age inclusive#and the sex ratio is not limited Signed informed consent form#willing or able to participate in all required study evaluations and procedures. SELENA-SLEDAI(Safety of Estrogens in Lupus Erythematosus National Assessment SLE Disease Activity Index) score ≥ 8 during the screening period.and if there is Hypo-complement or the Anti-dsDNA score, SELENA-SLEDAI disease activity score should be at least 6 at screening . Autoantibody-positive on a stable SLE treatment regimen for at least 30 days prior to Day 1, which consisted of any of the following (alone or in combination): cortical hormone,anti-malarials,non-steroidal anti inflammatory drugs (NSAIDs),or any immunosuppressive and immunomodulator therapy(i.e.,azathioprine,mycophenolate Exclusion Criteria: kidney disease ：Severe lupus nephritis 8 weeks prior to randomization (designed as:Urine protein>6g/24h or serum creatinine ( SCr>2.5mg/dL or 221umol/L ) or needing for hemodialysis or receipting high dose cortical hormone ≥14 days( metacortandracin>100mg/d or equivalent) Central nervous system disease caused by SLE or non SLE 8 weeks prior to randomization (including epilepsy、 mental disease、organic encephalopathy syndrome、cerebrovascular accident, encephalitis, central nervous system vasculitis; there are serious heart, liver, kidney and other important organs and blood, endocrine system diseases and medical history; Evaluation criteria for severity : Alanine aminotransferase#ALT#or aspartate aminotransferase (AST) ≥2 upper limit of normal (ULN); Creatinine Clearance (Ccr)<30ml/min; White Blood Cell Count(WBCs)<2.5x 10(9)/L; hemoglobin<85g/L; Platelets<50x 10(9)/L. Have a historically active hepatitis or active hepatitis or medical history,hepatitis B :Patients with positive HBsAg are excluded.;Hepatitis C: Patients with hepatitis C antibody positive are excluded; Immune deficiency, uncontrolled severe infection and patients with active or recurrent peptic ulcer; Pregnant , lactating women and men or women who have birth plans in the past 12 months ; Have a history of allergic reaction to human biological medicines. Receipt of live vaccine within 1 month; Have participated in any clinical trial in the first 28 days of the initial screening or 5 times half-life period of the study compound (taking the time for the elderly). Have received treatment with B cell targeted therapy such as Rituximab or Epratuzumab etc. Receipt of anti-tumor necrosis factor#interleukin receptor antagonist# Receipt of IV immunoglobulin(IVIG),prednisone>100mg/d more than 14 days or plasma exchange; There are active infections (such as herpes zoster, human immunodeficiency virus (HIV) virus infection, active tuberculosis, etc.) during the screening period; Patients have depression or the significant suicide ideation; Interleukin(IL)-2, thalidomide, Tripterygium wilfordii and traditional Chinese medicine preparation containing Tripterygium Wilfordii were used within 28 days before randomization Investigator considers candidates not appropriating for the study.

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RC18 160mg<br>Patients received the test group RC18 160mg weekly administered subcutaneously for 52 times. | Biological: RC18 160 mg plus standard therapy<br>* Standard therapy comprises any of the following (alone or in combination): corticosteroids, antimalarials, non-steroidal anti-inflammatory drugs (NSAIDs), and immunosuppressive and immunomodulator herapy(i.e.,azathioprine,mycophenolate ,cyclophosphamide,methotrexate,Tacrolimus ,ciclosporin )<br>* Other names: Standard therapy;|
| Placebo Comparator: Placebo<br>Patients received the test group Placebo weekly administered subcutaneously for 52 times. | Biological: Placebo plus standard therapy<br>* Standard therapy comprises any of the following (alone or in combination): corticosteroids, antimalarials, non-steroidal anti-inflammatory drugs (NSAIDs), and immunosuppressive and immunomodulator therapy(i.e.,azathioprine,mycophenolate ,cyclophosphamide,methotrexate,Tacrolimus ,ciclosporin )<br>* Other names: Standard therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SLE Responder Index (SRI) Response Rate | At Week 52 the percent of subjects with ≥ 4 point reduction from baseline in SELENA-SLEDAI score and increasing no more than 0.3 points in PGA and no new BILAG A organ domain score or 1 new BILAG B organ domain scores compared with baseline at the time of assessment | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of subjects with ≥ 4 point reduction from baseline in SELENA-SLEDAI score |  | Week 52 | 
| Mean Change From Baseline in Physician's global assessment(PGA) | Physician's global assessment, PGA.The measurement tool is Visual Analogue Scale/Score（VAS）.The doctor assesses participant's disease activity on a VAS of 0-100 mm on the questionnaire form.The higher values represent a worse outcome.There are not combined subscales. | Week 52 | 
| Percent of Subjects Whose Average Prednisone Dose Has Been Reduced by ≥ 25% From Baseline or ≤ 7.5 mg/Day，During Weeks 44 Through 52. |  | Week 44 through 52 | 
| Mean Change From Baseline in Serological Examination Index |  | week 52 | 
| The flare time after randomization |  | 52 weeks |