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

Phase 2

Completed

• Conditions: Systemic Lupus Erythematosus
• Interventions: Drug: SM934; Drug: Placebos

• Registration Number: NCT03951259
• Lead Sponsor: RenJi Hospital

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 available

Study Timeline

• Study First Submitted: 2019-05-14
• Study First Submitted QC: 2019-05-14
• Study First Posted: 2019-05-15
• Study Start: 2019-07-24
• Status Verified: 2023-10
• Primary Completion: 2023-10-13
• Study Completion: 2023-10-19
• Last Update Submitted: 2023-10-25
• Last Update Posted: 2023-10-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SM934 50mg	SM934	SM934 10mg（5 tablet）p.o. qd in combination with steroids
Placebo	Placebos	Placebo（5 tablets）p.o. qd in combination with steroids
SM934 10mg	SM934	SM934 10mg（1 tablet）+Placebo（4 tablets）p.o. qd in combination with steroids
SM934 30mg	SM934	SM934 10mg（3 tablet）+ Placebo（2 tablets）p.o. qd in combination with steroids

Primary Outcome Measures

Name	Time	Method
Percentage of Subjects with Treatment-Emergent Adverse Events (TEAEs) in each group	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	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	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 Outcome Measures

Name	Time	Method
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 who have at least 30% improvement in CLASI score compared to baseline.
Percentage of subjects with Proteinuria < 0.5g/24h in each group	Week 12	Percentage of subjects with 24hour urine protein level less than 0.5g in each group
Percentage change of anti-dsDNA level from baseline in each group	Week 12	Percentage change of anti-dsDNA level from baseline in each group
Change of SLICC/ACR from baseline	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	Week 12	Percentage of subjects and number of days with steroids dose equal or less to prednisone 7.5mg per day
Percentage change of SLEDAI-2000 and Physician Global Assessment (PGA) from baseline in each group	Week 12	Percentage change of SLEDAI-2000 and PGA from baseline in each group
Time to SLE flare and Percentage of subjects with SLE flare	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.
Percentage change of complement 3 (C3) and complement 4 (C4) from baseline in each group	Week 12	Percentage change of complement 3 (C3) and complement 4 (C4) from baseline in each group

Trial Locations

Locations (1)

Department of Rheumatology, RenJi Hospital, School of Medicine, Shanghai JiaoTong University; 🇨🇳 Shanghai, Shanghai, China