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Safety and Efficacy of SM934 Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus

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ClinicalTrials.gov Identifier: NCT03951259
Recruitment Status : Recruiting
First Posted : May 15, 2019
Last Update Posted : September 4, 2019
Sponsor:
Collaborator:
Jiangsu ZuoYou Medicine Co., Ltd.
Information provided by (Responsible Party):
RenJi Hospital

Tracking Information
First Submitted Date  ICMJE May 14, 2019
First Posted Date  ICMJE May 15, 2019
Last Update Posted Date September 4, 2019
Actual Study Start Date  ICMJE July 24, 2019
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 15, 2019)
  • Percentage of Subjects with Lupus Low Disease Activity Score (LLDAS) in each group [ Time Frame: Week 12 ]
    LLDAS is defined as meeting the following criteria:
    1. SLEDAI-2K ≤4, with no activity in major organ systems (renal, CNS, cardiopulmonary, vasculitis), and no reported fever, hemolytic anemia, or gastrointestinal activity)
    2. No new disease activity compared with the previous assessment (no new British isles lupus assessment group (BILAG) A domain score or no more than 1 new BILAG B domain score)
    3. PGA ≤1 on a 0-3 scale visual visual analogue scale (VAS)
    4. A current prednisone (or equivalent) dose of ≤7.5 mg daily
    5. Well-tolerated standard maintenance doses of permitted immunosuppressive drugs
  • Percentage of Subjects with Systemic Lupus Erythematosus Responder Index - 4 (SRI-4) response in each group [ Time Frame: Week 12 ]
    SRI-4 response is defined as:
    1. ≥ 4-point reduction from baseline in SLEDAI-2K score
    2. No new BILAG A and no more than 1 new BILAG B domain score
    3. No worsening from baseline in the PGA (<10% worsening from baseline).
  • Percentage of Subjects with Treatment-Emergent Adverse Events (TEAEs) in each group [ Time Frame: Baseline through Week 13 ]
    Percentage of Subjects with TEAEs in each group
Original Primary Outcome Measures  ICMJE
 (submitted: May 14, 2019)
  • Pecentage of Subjects with LLDAS in each group [ Time Frame: Week 12 ]
    LLDAS is defined as meeting the following criteria:
    1. SLEDAI-2K ≤4, with no activity in major organ systems (renal, CNS, cardiopulmonary, vasculitis), and no reported fever, hemolytic anemia, or gastrointestinal activity)
    2. No new disease activity compared with the previous assessment (no new British isles lupus assessment group (BILAG) A domain score or no more than 1 new BILAG B domain score)
    3. PGA ≤1 on a 0-3 scale VAS
    4. A current prednisone (or equivalent) dose of ≤7.5 mg daily
    5. Well-tolerated standard maintenance doses of permitted immunosuppressive drugs
  • Pecentage of Subjects with SRI-4 response in each group [ Time Frame: Week 12 ]
    SRI-4 response is defined as:
    1. ≥ 4-point reduction from baseline in SLEDAI-2K score
    2. No new BILAG A and no more than 1 new BILAG B domain score
    3. No worsening from baseline in the PGA (<10% worsening from baseline).
  • Percentage of Subjects with Treatment-Emergent Adverse Events (TEAEs) in each group [ Time Frame: Baseline through Week 13 ]
    Percentage of Subjects with TEAEs in each group
Change History Complete list of historical versions of study NCT03951259 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2019)
  • Percentage change of SLEDAI-2000 and Physician Global Assessment (PGA) from baseline in each group [ Time Frame: Week 12 ]
    Percentage change of SLEDAI-2000 and PGA from baseline in each group
  • Percentage of Subjects with 30% improvement in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) score in each group [ Time Frame: Week 12 ]
    Percentage of subjects who have at least 30% improvement in CLASI score compared to baseline.
  • Change of SLICC/ACR from baseline [ Time Frame: Week 12 ]
    Change of SLICC/ACR score from baseline
  • Percentage of subjects and number of days with steroids dose equal or less to prednisone 7.5mg per day [ Time Frame: Week 12 ]
    Percentage of subjects and number of days with steroids dose equal or less to prednisone 7.5mg per day
  • Percentage of subjects with Proteinuria < 0.5g/24h in each group [ Time Frame: Week 12 ]
    Percentage of subjects with 24hour urine protein level less than 0.5g in each group
  • Percentage change of complement 3 (C3) and complement 4 (C4) from baseline in each group [ Time Frame: Week 12 ]
    Percentage change of complement 3 (C3) and complement 4 (C4) from baseline in each group
  • Percentage change of anti-dsDNA level from baseline in each group [ Time Frame: Week 12 ]
    Percentage change of anti-dsDNA level from baseline in each group
  • Time to SLE flare and Percentage of subjects with SLE flare [ Time Frame: Baseline through week 12 ]
    SLE flare is defined as: Compared to baseline, one new BILAG A or more than 1 new BILAG B domain score. Time to SLE flare is defined as the date of SLE flare minus the date of treatment initiation plus one.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2019)
  • Percentage change of SLEDAI-2k and PGA from baseline in each group [ Time Frame: Week 12 ]
    Percentage change of SLEDAI-2k and PGA from baseline in each group
  • Percentage of Subjects with 30% improvement in CLASI score in each group [ Time Frame: Week 12 ]
    Percentage of subjects who have at least 30% improvement in CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index) score compared to baseline.
  • Change of SLICC/ACR from baseline [ Time Frame: Week 12 ]
    Change of SLICC/ACR score from baseline
  • Percentage of subjects and number of days with steroids dose equal or less to prednisone 7.5mg per day [ Time Frame: Week 12 ]
    Percentage of subjects and number of days with steroids dose equal or less to prednisone 7.5mg per day
  • Percentage of subjects with Proteinuria < 0.5g/24h in each group [ Time Frame: Week 12 ]
    Percentage of subjects with 24hour urine protein level less than 0.5g in each group
  • Percentage change of complement 3 (C3) and complement 4 (C4) from baseline in each group [ Time Frame: Week 12 ]
    Percentage change of complement 3 (C3) and complement 4 (C4) from baseline in each group
  • Percentage change of anti-dsDNA level from baseline in each group [ Time Frame: Week 12 ]
    Percentage change of anti-dsDNA level from baseline in each group
  • Time to SLE flare and Percentage of subjects with SLE flare [ Time Frame: Baseline through week 12 ]
    SLE flare is defined as: Compared to baseline, one new BILAG A or more than 1 new BILAG B domain score. Time to SLE flare is defined as the date of SLE flare minus the date of treatment initiation plus one.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of SM934 Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus
Official Title  ICMJE A Randomised, Double-blind, Placebo-controlled, Phase 2 Study Evaluating the Safety and Efficacy of SM934 in Adult Subjects With Active Systemic Lupus Erythematosus
Brief Summary This is a single-center, randomized, double-blind, placebo-controlled, phase 2 study. The purpose of the study is to initially evaluate the safety and efficacy of SM934 combined with steroids compared to placebo in adult subjects with active systemic lupus erythematosus (SLE) over a 12-week period.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Systemic Lupus Erythematosus
Intervention  ICMJE
  • Drug: SM934
    In this study, the investigating intervention is oral administration of SM934. SM934 is a water-soluble derivative of arteminisin, which exerts immunosuppressive functions in vitro and in vivo.
  • Drug: Placebos
    The placebo pills are made identical to the investigating SM934 in appearance.
Study Arms  ICMJE
  • Experimental: SM934 10mg
    SM934 10mg(1 tablet)+Placebo(4 tablets)p.o. qd in combination with steroids
    Intervention: Drug: SM934
  • Experimental: SM934 30mg
    SM934 10mg(3 tablet)+ Placebo(2 tablets)p.o. qd in combination with steroids
    Intervention: Drug: SM934
  • Experimental: SM934 50mg
    SM934 10mg(5 tablet)p.o. qd in combination with steroids
    Intervention: Drug: SM934
  • Placebo Comparator: Placebo
    Placebo(5 tablets)p.o. qd in combination with steroids
    Intervention: Drug: Placebos
Publications * Hou LF, He SJ, Wang JX, Yang Y, Zhu FH, Zhou Y, He PL, Zhang Y, Yang YF, Li Y, Tang W, Zuo JP. SM934, a water-soluble derivative of arteminisin, exerts immunosuppressive functions in vitro and in vivo. Int Immunopharmacol. 2009 Dec;9(13-14):1509-17. doi: 10.1016/j.intimp.2009.09.003. Epub 2009 Sep 19.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 14, 2019)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2020
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age: 18 to 70;
  • Have a clinical diagnosis of SLE according to SLICC-2012 classification criteria;
  • Have active SLE with SLEDAI-2k ≥ 6;
  • Have positive anti-nuclear antibody (ANA) test results;
  • Are on a stable steroids treatment (equals to prednison more than 7.5mg daily but no more than 0.5mg/kg/d) for SLE for at least 30 days prior to first dose of study agent;
  • Females of childbearing age are willing to use appropriate contraception;
  • Are voluntary to to provide and sign voluntary informed consent is given;

Exclusion Criteria:

  • Have any unstable or progressive manifestation of SLE, including but not limited to Central nervous system (CNS) involvement, transverse myelitis, systemic vasculitis, vasculitis with GI involvement, severe or rapidly progressive lupus nephritis, lupus nephritis with proteinuria > 3g/24h, pulmonary hemorrhage, myocarditis;
  • Have abnormal liver function test or renal function test: Alanine aminotransferase(ALT)or aspartate aminotransferase (AST) >2 upper limit of normal (ULN); Gamma-glutamyl transferase (GGT) >1.5 ULN; Creatinine or Blood urea nitrogen (BUN) >1.5 ULN;
  • Have a history of acute myocardiac infarction, unstable angina, severe arrhythmias within 6 months prior to first dose of study agent;
  • Have any major illness/condition or evidence of an unstable clinical condition not due to SLE (eg, cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, psychiatric), which, in the Investigator's judgment, will substantially increase the risk to the participant if he or she participates in the study;
  • Have any acute or chronic infectious disease, which requires medical intervention;
  • Have a history of cancer within the last 5 years, except for adequately treated skin cancer, or carcinoma in situ of the uterine cervix;
  • Have a planned surgical procedure;
  • Have received a biologic investigational agent in the past one year;
  • Have received the following treatment within 30 days prior to first dose of study agent: live vaccine; change of glucocorticoids dose; IV, intra-muscular (IM), intra-articular (IA) administration of glucocorticoids; other immunosuppressants/immunomodulators; anti-malarial drugs; traditional medicines which has proved to be effective in SLE;
  • Have had a major organ transplant;
  • Have a history of HIV, or test positive at screening for HIV;
  • Test positive for Hepatitis B virus (HBV)-DNA or Hepatitis C virus (HCV)-RNA;
  • Have or have had a substance abuse (drug, alcohol) problem in the past one year;
  • Are currently using or planned to use estrogen-containing contraceptive methods;
  • Have enrolled in an investigational study within 3 months prior to first dose of study agent;
  • Investigator considers candidates not appropriating for the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Nan Shen, MD & PhD +86-21-63260477 nanshensibs@gmail.com
Contact: Huihua Ding, MD +86-21-53882280 dinghuihua@outlook.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03951259
Other Study ID Numbers  ICMJE SM934
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party RenJi Hospital
Study Sponsor  ICMJE RenJi Hospital
Collaborators  ICMJE Jiangsu ZuoYou Medicine Co., Ltd.
Investigators  ICMJE Not Provided
PRS Account RenJi Hospital
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP