Study of Recombinant Human B Lymphocyte(RC18) Administered Subcutaneously to Subjects With Systemic Lupus Erythematosus(SLE)
Primary Purpose
Systemic Lupus Erythematosus
Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Placebo plus standard therapy
RC18 160 mg plus standard therapy
Sponsored by
About this trial
This is an interventional treatment trial for Systemic Lupus Erythematosus
Eligibility Criteria
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.
Sites / Locations
- Remegen,ltd.
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
RC18 160mg
Placebo
Arm Description
Patients received the test group RC18 160mg weekly administered subcutaneously for 52 times.
Patients received the test group Placebo weekly administered subcutaneously for 52 times.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Percent of subjects with ≥ 4 point reduction from baseline in SELENA-SLEDAI score
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.
Percent of Subjects Whose Average Prednisone Dose Has Been Reduced by ≥ 25% From Baseline or ≤ 7.5 mg/Day,During Weeks 44 Through 52.
Mean Change From Baseline in Serological Examination Index
The flare time after randomization
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04082416
Brief Title
Study of Recombinant Human B Lymphocyte(RC18) Administered Subcutaneously to Subjects With Systemic Lupus Erythematosus(SLE)
Official Title
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).
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
October 16, 2019 (Actual)
Primary Completion Date
April 24, 2022 (Actual)
Study Completion Date
June 30, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
RemeGen Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Lupus Erythematosus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
335 (Actual)
8. Arms, Groups, and Interventions
Arm Title
RC18 160mg
Arm Type
Experimental
Arm Description
Patients received the test group RC18 160mg weekly administered subcutaneously for 52 times.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients received the test group Placebo weekly administered subcutaneously for 52 times.
Intervention Type
Biological
Intervention Name(s)
Placebo plus standard therapy
Other Intervention Name(s)
Standard therapy
Intervention Description
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 )
Intervention Type
Biological
Intervention Name(s)
RC18 160 mg plus standard therapy
Other Intervention Name(s)
Standard therapy
Intervention Description
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 )
Primary Outcome Measure Information:
Title
SLE Responder Index (SRI) Response Rate
Description
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
Time Frame
Week 52
Secondary Outcome Measure Information:
Title
Percent of subjects with ≥ 4 point reduction from baseline in SELENA-SLEDAI score
Time Frame
Week 52
Title
Mean Change From Baseline in Physician's global assessment(PGA)
Description
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.
Time Frame
Week 52
Title
Percent of Subjects Whose Average Prednisone Dose Has Been Reduced by ≥ 25% From Baseline or ≤ 7.5 mg/Day,During Weeks 44 Through 52.
Time Frame
Week 44 through 52
Title
Mean Change From Baseline in Serological Examination Index
Time Frame
week 52
Title
The flare time after randomization
Time Frame
52 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fengchun Zhang, M.D.
Organizational Affiliation
Peking Union Medical College Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Remegen,ltd.
City
Yantai
State/Province
Shandong
Country
China
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Study of Recombinant Human B Lymphocyte(RC18) Administered Subcutaneously to Subjects With Systemic Lupus Erythematosus(SLE)
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