A Randomised, Double-blind, Placebo-controlled, Phase 2 Study Evaluating the Safety and Efficacy of SM934 in Adult Subjects With Active Systemic Lupus Erythematosus
Overview
- Phase
- Phase 2
- Intervention
- SM934
- Conditions
- Systemic Lupus Erythematosus
- Sponsor
- RenJi Hospital
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Percentage of Subjects with Treatment-Emergent Adverse Events (TEAEs) in each group
- Status
- Completed
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
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;
Arms & Interventions
SM934 10mg
SM934 10mg（1 tablet）+Placebo（4 tablets）p.o. qd in combination with steroids
Intervention: SM934
SM934 30mg
SM934 10mg（3 tablet）+ Placebo（2 tablets）p.o. qd in combination with steroids
Intervention: SM934
SM934 50mg
SM934 10mg（5 tablet）p.o. qd in combination with steroids
Intervention: SM934
Placebo
Placebo（5 tablets）p.o. qd in combination with steroids
Intervention: Placebos
Outcomes
Primary Outcomes
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
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).
Secondary Outcomes
- Percentage of Subjects with 30% improvement in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) score in each group(Week 12)
- Percentage of subjects with Proteinuria < 0.5g/24h in each group(Week 12)
- Percentage change of anti-dsDNA level from baseline in each group(Week 12)
- Change of SLICC/ACR from baseline(Week 12)
- Percentage of subjects and number of days with steroids dose equal or less to prednisone 7.5mg per day(Week 12)
- Time to SLE flare and Percentage of subjects with SLE flare(Baseline through week 12)
- Percentage change of SLEDAI-2000 and Physician Global Assessment (PGA) from baseline in each group(Week 12)
- Percentage change of complement 3 (C3) and complement 4 (C4) from baseline in each group(Week 12)