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出境医 / 临床实验 / Safety and Efficacy of SM934 Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus
Safety and Efficacy of SM934 Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus
Study Description
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Systemic Lupus Erythematosus | Drug: SM934 Drug: Placebos | Phase 2 |
Study Design
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 48 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | July 24, 2019 |
| Estimated Primary Completion Date : | December 31, 2020 |
| Estimated Study Completion Date : | December 31, 2020 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
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Experimental: SM934 10mg
SM934 10mg（1 tablet）+Placebo（4 tablets）p.o. qd in combination with steroids
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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.
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Experimental: SM934 30mg
SM934 10mg（3 tablet）+ Placebo（2 tablets）p.o. qd in combination with steroids
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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.
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Experimental: SM934 50mg
SM934 10mg（5 tablet）p.o. qd in combination with steroids
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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.
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Placebo Comparator: Placebo
Placebo（5 tablets）p.o. qd in combination with steroids
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Drug: Placebos
The placebo pills are made identical to the investigating SM934 in appearance.
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Outcome Measures
Primary Outcome Measures :
- 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:
- SLEDAI-2K ≤4, with no activity in major organ systems (renal, CNS, cardiopulmonary, vasculitis), and no reported fever, hemolytic anemia, or gastrointestinal activity)
- 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)
- PGA ≤1 on a 0-3 scale visual visual analogue scale (VAS)
- A current prednisone (or equivalent) dose of ≤7.5 mg daily
- 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:
- ≥ 4-point reduction from baseline in SLEDAI-2K score
- No new BILAG A and no more than 1 new BILAG B domain score
- 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
Secondary Outcome Measures :
- 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.
Eligibility Criteria
| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations
Contacts
| Contact: Nan Shen, MD & PhD | +86-21-63260477 | nanshensibs@gmail.com | |
| Contact: Huihua Ding, MD | +86-21-53882280 | dinghuihua@outlook.com |
Locations
| China, Shanghai | |
| Department of Rheumatology, RenJi Hospital, School of Medicine, Shanghai JiaoTong University | Recruiting |
| Shanghai, Shanghai, China, 200001 | |
| Contact: Nan Shen, MD & PhD +86-21-63260477 nanshensibs@gmail.com | |
| Contact: Huihua Ding, MD +86-21-53882280 dinghuihua@outlook.com | |
| Principal Investigator: Nan Shen, MD & PhD | |
| Sub-Investigator: Qiang Guo, MD & PhD | |
| Sub-Investigator: Min Dai, MD | |
| Sub-Investigator: Huihua Ding, MD | |
Sponsors and Collaborators
RenJi Hospital
Jiangsu ZuoYou Medicine Co., Ltd.
| Tracking Information | |||||||||
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| 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 |
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| Original Primary Outcome Measures ICMJE |
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| Change History | |||||||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE |
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| 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 |
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| Condition ICMJE | Systemic Lupus Erythematosus | ||||||||
| Intervention ICMJE |
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| Study Arms ICMJE |
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| 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. | ||||||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||||
| Recruitment Status ICMJE | Recruiting | ||||||||
| Estimated Enrollment ICMJE |
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:
Exclusion Criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 18 Years to 70 Years (Adult, Older Adult) | ||||||||
| Accepts Healthy Volunteers ICMJE | No | ||||||||
| Contacts ICMJE |
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| 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 |
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| IPD Sharing Statement ICMJE |
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| 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 | ||||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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