Evaluate the Efficacy and Safety of Orelabrutinib in Adult Patients With Systemic Lupus Erythematosus
- Conditions
- Systemic Lupus Erythematosus, SLE
- Interventions
- Registration Number
- NCT05688696
- Lead Sponsor
- Beijing InnoCare Pharma Tech Co., Ltd.
- Brief Summary
This is a phase IIb, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of orelabrutinib in adult subjects with SLE who are receiving standard of care (SOC) therapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 186
- have had a detailed understanding of the nature, significance, potential benefits, potential risks, and procedures of the study, and voluntarily signed a written Informed Consent Form (ICF).
- Males or females aged≥18 and ≤75 years.
- Have a clinical diagnosis of SLE 6 months prior to signing the ICF, meeting at least 4 of the 11 American College of Rheumatology (ACR) classification criteria for SLE.
- SLEDAI-2K≥8 at screening.
- Are on a stable SLE SOC therapy consisting of any of the following medications for a period of at least 30 days prior to the first dose: glucocorticoid, and/or anti-malarials, and/or immunosuppressive agents.
- Have a positive test for anti-dsDNA antibody (> normal range) and/or anti-nuclear antibody (ANA) and/or anti-Smith antibody at screening.
- Women of childbearing potential must take a complementary barrier method of contraception in combination with a highly effective method of contraception at screening, throughout the trial, and within 90 days after the last dose of the investigational agent. In this trial.
Medical conditions:
-
Pregnant or lactating women, and men or women who have birth plans in the past 12 months.
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Have neuropsychiatric systemic lupus erythematosus (NPSLE) within 6 months prior to the first dose, including seizures, psychosis, organic brain syndrome, cerebrovascular accident, cranial neuropathy, cerebritis, cerebral vasculitis or lupus headache.
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Have severe lupus nephritis, or have required hemodialysis or high-dose glucocorticoid within 90 days prior to the first dose.
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Have autoimmune diseases other than SLE (excluding secondary Sjogren's syndrome).
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Have a history of any non-SLE disease that has required treatment with oral or intravenous or intramuscular or subcutaneous injection glucocorticoids for more than a total of 2 weeks within the last 24 weeks prior to signing the ICF.
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Have a history of or current diagnosis of Central Nervous System (CNS) diseases.
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Have clinically documented cardiovascular diseases that are obviously unstable or not effectively treated.
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Have significant active lung diseases (e.g., interstitial lung disease, obstructive pulmonary disease).
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Have severe hepatobiliary diseases.
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Have a history of malignant neoplasm.
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Have a history of a major organ transplant or hematopoietic stem cell/marrow transplant.
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Have known allergies to any component of the investigational agent as described in the Protocol.
Concomitant medication and surgery:
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Have received rituximab, epratuzumab, or any other B cell-depleting therapy within 12 months prior to randomization.
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Have received cyclophosphamide and chlorambucil within 6 months prior to randomization.
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Have received belimumab, tumor necrosis factor (TNF) blockers, interleukin receptor blockers or other biological agents within 3 months prior to randomization (or 5 half-lives, whichever is longer).
Lab tests:
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Have a positive test for human immunodeficiency virus (HIV) antibody.
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Have a positive test for Hepatitis B Surface Antigen (HBsAg) or hepatitis C antibody, or have a positive test for hepatitis B virus (HBV) DNA by Polymerase Chain Reaction (PCR) if positive for Hepatitis B Core Antibody (HBcAb).
-
Have abnormal tissue or organ function, meeting any of the following at screening:
- Absolute neutrophil count (ANC) < 1.5 × 10^9/L; hemoglobin < 90 g/L; lymphocyte count < 0.8 × 10^9 /L.
- Calculated estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation < 45 mL/min/1.73 m2.
Others:
-
Have other conditions that are not appropriate for participation in the trial as considered by the investigator.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Orelabrutinib Lower Dose Orelabrutinib (Low Dose) - Orelabrutinib Higher Dose Orelabrutinib (High Dose) - Placebo Orelabrutinib Placebo -
- Primary Outcome Measures
Name Time Method SLE Responder Index (SRI) - 4 response rate Week 48 SRI-4 response is defined as: 1)≥4 point reduction from baseline in SLE disease activity index-2000 (SLEDAI-2K) score; 2) no worsening (increase of \<0.3 points from baseline) in Physician's Global Assessment (PGA); 3) no new A organ domain score or no more than 1 new B organ domain scores compared with baseline in British Isles Lupus Assessment Group (BILAG)-2004.
- Secondary Outcome Measures
Name Time Method British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response rate Week 48 BICLA response is defined as: 1) In BILAG-2004, reduction of all baseline A to B/C/D and baseline B to C/D, and no worsening in other organ systems (as defined by no new A organ domain score or no more than 1 new B organ domain scores); 2) No worsening from baseline in SLEDAI-2K, where worsening is defined as an increase from baseline of \>0 points in SLEDAI-2K; 3) No worsening (increase of \<0.3 points from baseline) in PGA.
SLE Responder Index (SRI) - 6 response rate Week 48 SRI-6 response is defined as: 1)≥6 point reduction from baseline in SLE disease activity index-2000 (SLEDAI-2K) score; 2) no worsening (increase of \<0.3 points from baseline) in Physician's Global Assessment (PGA); 3) no new A organ domain score or no more than 1 new B organ domain scores compared with baseline in British Isles Lupus Assessment Group (BILAG)-2004.
Time to 1st flare Week 48 The proportion of subjects whose average prednisone dose has been reduced by≥25% from baseline to ≤7.5 mg/day Week 48 Changes from baseline in the levels of complement C3, complement C4, and anti-dsDNA antibody Week 48 Adopt the unified unit standard of central laboratory testing
Treatment Emergent Adverse Events, Treatment Related Adverse Events, Treatment Emergent Serious Adverse Events, Treatment Related Serious Adverse Events. Up to Week 52 Mean change from baseline in the 36-Item Short Form Health Survey (SF-36) scores (The SF-36 consists of eight domains. Each domain score ranges from 0-100. The higher the score, the better the health. ) Week 48
Trial Locations
- Locations (41)
Jilin Provincial People's Hospital
🇨🇳Changchun, Jilin, China
Daqing Oilfield General Hospital
🇨🇳Daqing, Heilongjiang, China
Yiyang Central Hospital
🇨🇳Yiyang, Hunan, China
Jiujiang NO.1 People's Hospital
🇨🇳Jiujiang, Jiangxi, China
Xuzhou Central Hospital
🇨🇳Xuzhou, Jiangsu, China
Affiliated Hospital of Inner Mongolia Medical University
🇨🇳Hohhot, Nei Monggol Autonomous Region, China
The First Hospital of Shanxi Medical University
🇨🇳Taiyuan, Shanxi, China
Wenzhou People's Hospital
🇨🇳Wenzhou, Zhejiang, China
The first affiliated hospital of bengbu medical college
🇨🇳Bengbu, Anhui, China
Beijing Friendship Hospital, Capital Medical University
🇨🇳Beijing, Beijing, China
The first affiliated hospital of shantou university medical college
🇨🇳Shantou, Guangdong, China
The First Affiliated Hospital of Henan University of Science and Technology
🇨🇳Luoyang, Henan, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
Shengjing Hospital of china medical university
🇨🇳Shenyang, Liaoning, China
Linyi People's Hospital
🇨🇳Linyi, Shandong, China
The Second Hospital of Shanxi Medical University
🇨🇳Taiyuan, Shanxi, China
The First Affiliated Hospital of Xi 'an Jiaotong University
🇨🇳Xi'an, Shanxi, China
Tianjin Medical University General Hospital
🇨🇳Tianjin, Tianjin, China
Xinjiang Uygur Autonomous Region People's Hospital
🇨🇳Ürümqi, Xinjiang, China
The First Hospital of Ningbo
🇨🇳Ningbo, Zhejiang, China
The First People's Hospital of Wenling
🇨🇳Wenling, Zhejiang, China
The Third People's Hospital of Huzhou
🇨🇳Huzhou, Zhejiang, China
Peking University People's Hospital
🇨🇳Beijing, Beijing, China
China-Japan Friendship Hospital
🇨🇳Beijing, Beijing, China
The First Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
The Seventh Affiliated Hospital, Sun Yat-sen University
🇨🇳Shenzhen, Guangdong, China
The First Affiliated Hospital of XiaMen University
🇨🇳Xiamen, Fujian, China
The First Affiliated Hospital,Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
Affiliated Hospital of Guilin Medical University
🇨🇳Guilin, Guangxi Zhuang Autonomous Region, China
Affiliated Hospital of HeBei University
🇨🇳Baoding, Hebei, China
Hebei People's Hospital
🇨🇳Shijiazhuang, Hebei, China
The first hospital of Qiqihar
🇨🇳Qiqihar, Heilongjiang, China
First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
The Second XIANGYA Hospital Of Central South University
🇨🇳Changsha, Hunan, China
Zhuzhou Central Hospital
🇨🇳Zhuzhou, Hunan, China
The Second Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
Renji Hospital, Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, Shanghai, China
Affiliated Hospital of Binzhou Medical College
🇨🇳Binzhou, Shandong, China
Jining First People's Hospital
🇨🇳Jining, Shandong, China
Changhai Hospital of Shanghai
🇨🇳Shanghai, Shanghai, China