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

NCT03951259 | Completed Phase 2

• 1 other identifier: SM934
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (3)

• Percentage of Subjects with Lupus Low Disease Activity Score (LLDAS) in each group

  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

  Week 12

• Percentage of Subjects with Systemic Lupus Erythematosus Responder Index - 4 (SRI-4) response in each group

  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).

  Week 12

• Percentage of Subjects with Treatment-Emergent Adverse Events (TEAEs) in each group

  Percentage of Subjects with TEAEs in each group

  Baseline through Week 13

Secondary Outcomes (8)

• Percentage change of SLEDAI-2000 and Physician Global Assessment (PGA) from baseline in each group

  Week 12

• Percentage of Subjects with 30% improvement in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) score 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

• Percentage of subjects with Proteinuria < 0.5g/24h in each group

  Week 12

Study Arms (4)

SM934 10mg

EXPERIMENTAL

SM934 10mg（1 tablet）+Placebo（4 tablets）p.o. qd in combination with steroids

Drug: SM934

SM934 30mg

EXPERIMENTAL

SM934 10mg（3 tablet）+ Placebo（2 tablets）p.o. qd in combination with steroids

Drug: SM934

SM934 50mg

EXPERIMENTAL

SM934 10mg（5 tablet）p.o. qd in combination with steroids

Drug: SM934

Placebo

PLACEBO COMPARATOR

Placebo（5 tablets）p.o. qd in combination with steroids

Drug: Placebos

Interventions

SM934 DRUG

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.

SM934 10mg; SM934 30mg; SM934 50mg

Placebos DRUG

The placebo pills are made identical to the investigating SM934 in appearance.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• RenJi Hospital: lead
• Jiangsu ZuoYou Medicine Co., Ltd.: collaborator

Study Sites (1)

Department of Rheumatology, RenJi Hospital, School of Medicine, Shanghai JiaoTong University

Shanghai, Shanghai Municipality, 200001, China

Location

Related Publications (1)

• 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.

  PMID: 19772931 BACKGROUND

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

beta-aminoarteether maleate

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Nan Shen, MD & PhD

  Shanghai Jiao Tong University School of Medicine affiliated Renji Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2019
• First Posted: May 15, 2019
• Study Start: July 24, 2019
• Primary Completion: October 13, 2023
• Study Completion: October 19, 2023
• Last Updated: October 27, 2023

Record last verified: 2023-10

Locations

CN (1)