Clinical trial NCT03951259: Safety and Efficacy of SM934 Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus
Official title: A Randomised, Double-blind, Placebo-controlled, Phase 2 Study Evaluating the Safety and Efficacy of SM934 in Adult Subjects With Active Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
Collaborators: name: Jiangsu ZuoYou Medicine Co., Ltd.
First posted: 2019-05-15
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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;
* 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.

Primary outcomes:
measure: Percentage of Subjects with Lupus Low Disease Activity Score (LLDAS) in each group
timeFrame: Week 12
measure: Percentage of Subjects with Systemic Lupus Erythematosus Responder Index - 4 (SRI-4) response in each group
timeFrame: Week 12
measure: Percentage of Subjects with Treatment-Emergent Adverse Events (TEAEs) in each group
timeFrame: Baseline through Week 13
Secondary outcomes:
measure: Percentage change of SLEDAI-2000 and Physician Global Assessment (PGA) from baseline in each group
timeFrame: Week 12
measure: Percentage of Subjects with 30% improvement in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) score in each group
timeFrame: Week 12
measure: Change of SLICC/ACR from baseline
timeFrame: Week 12
measure: Percentage of subjects and number of days with steroids dose equal or less to prednisone 7.5mg per day
timeFrame: Week 12
measure: Percentage of subjects with Proteinuria < 0.5g/24h in each group
timeFrame: Week 12
measure: Percentage change of complement 3 (C3) and complement 4 (C4) from baseline in each group
timeFrame: Week 12
measure: Percentage change of anti-dsDNA level from baseline in each group
timeFrame: Week 12
measure: Time to SLE flare and Percentage of subjects with SLE flare
timeFrame: Baseline through week 12
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Rheumatology, RenJi Hospital, School of Medicine, Shanghai JiaoTong University
state: Shanghai
Study officials:
affiliation: Shanghai Jiao Tong University School of Medicine affiliated Renji Hospital
name: Nan Shen, MD & PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.