Study of RC18 Administered Subcutaneously to Subjects With Systemic Lupus Erythematosus(SLE)

• ClinicalTrials.gov Identifier: NCT02885610
• Recruitment Status: Completed
• First Posted: August 31, 2016
• Last Update Posted: March 4, 2020
• Sponsor: RemeGen Co., Ltd.
• Information provided by (Responsible Party): RemeGen Co., Ltd.

Tracking Information

• First Submitted Date: August 26, 2016
• First Posted Date: August 31, 2016
• Last Update Posted Date: March 4, 2020
• Study Start Date: December 2015
• Actual Primary Completion Date: June 11, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 30, 2016)

SLE Responder Index (SRI) Response Rate [ Time Frame: Week 48 ]

At Week 48, 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.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: August 30, 2016): Percent of subjects with ≥ 4 point reduction from baseline in SELENA SLEDAI score [ Time Frame: Week 48 ]
• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: August 30, 2016)

• Mean Change From Baseline in PGA [ Time Frame: Week 48 ]
• Percent of Subjects Whose Average Prednisone Dose Has Been Reduced by ≥ 25% From Baseline or ≤ 7.5 mg/Day During Weeks 44 Through 48 [ Time Frame: Week 44 through 48 ]
• Mean Change From Baseline in Serological Examination Index(IgG、IgA、IgM) CD19+、Anti-dsDNA 、Complent C3、C4 [ Time Frame: week 48 ]

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Study of RC18 Administered Subcutaneously to Subjects With Systemic Lupus Erythematosus(SLE)
• Official Title: A Phase IIb , Placebo-Controlled ,Multi-Center, Randomized, Double-Blind, Dose-explorating Trial of RC18,a Recombinant Human B Lymphocyte Stimulating Factor Receptor-Antibody Fusion Protein in Subjects With Systemic Lupus Erythematosus (SLE).
• 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, Besides ,to provide dose basis for follow-up clinical trials.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Systemic Lupus Erythematosus

Intervention

• Biological: Placebo plus standard therapy
  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,leflunomide, Tacrolimus ,ciclosporin )
  Other Name: Standard therapy
• Biological: RC18 80 mg plus standard therapy
  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,leflunomide, Tacrolimus ,ciclosporin )
  Other Name: Standard therapy
• Biological: RC18 160 mg plus standard therapy
  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,leflunomide, Tacrolimus ,ciclosporin )
  Other Name: Standard therapy
• Biological: RC18 240 mg plus standard therapy
  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,leflunomide, Tacrolimus ,ciclosporin )
  Other Name: Standard therapy

Study Arms

• Placebo Comparator: Placebo Comparator
  Placebo SC plus standard therapy; placebo once weekly ,and total of 48 doses
  Intervention: Biological: Placebo plus standard therapy
• Experimental: RC18 80 mg plus standard therapy
  RC18 80 mg/kg SC plus standard therapy RC18 80 mg SC once weekly X 48 doses
  Intervention: Biological: RC18 80 mg plus standard therapy
• Experimental: RC18 160 mg plus standard therapy
  RC18 160 mg/kg SC plus standard therapy RC18 160 mg SC once weekly X 48 doses
  Intervention: Biological: RC18 160 mg plus standard therapy
• Experimental: RC18 240 mg plus standard therapy
  RC18 240 mg/kg SC plus standard therapy RC18 240 mg SC once weekly X 48 doses
  Intervention: Biological: RC18 240 mg plus standard therapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 18, 2019): 249
• Original Estimated Enrollment (submitted: August 30, 2016): 160
• Actual Study Completion Date: July 9, 2019
• Actual Primary Completion Date: June 11, 2019 (Final data collection date for primary outcome measure)

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 hypocomlement 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 ,cyclophosphamide,methotrexate,leflunomide, Tacrolimus ,ciclosporin ).

Exclusion Criteria:

• Severe lupus nephritis within two months(designed as:Urine protein>6g/24h or serum creatinine ( SCr）>2.5mg/dL or 221umol/L ) or needing for hemodialysis or recepting high dose cortical hormone ≥14 days( metacortandracin>100mg/d or equivalent)
• Central nervous system disease caused by SLE or non SLE within two months (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 :

1. Alanine aminotransferase（ALT）or aspartate aminotransferase (AST) ≥2 upper limit of normal (ULN);
2. Creatinine Clearance (Ccr)<30ml/min;
3. White Blood Cell Count(WBCs)<2.5x 10(9)/L;
4. hemoglobin<85g/L;

5. 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;
   • Investigator considers candidates not appropriating for the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT02885610
• Other Study ID Numbers: C005 SLECLLI
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: RemeGen Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: RemeGen Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Fengchun Zhang; Peking Union Medical College Hospital

• PRS Account: RemeGen Co., Ltd.
• Verification Date: March 2020