Evaluate the Efficacy and Safety of Orelabrutinib in Adult Patients With Systemic Lupus Erythematosus

A Phase IIb, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Orelabrutinib in Adult Patients With Systemic Lupus Erythematosus

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.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus, SLE
• Intervention / Treatment: Drug: Orelabrutinib (Low Dose); Drug: Orelabrutinib (High Dose); Drug: Orelabrutinib Placebo

• Study Type: Interventional
• Enrollment (Estimated): 186
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhanguo Li, PhD; Phone Number: 010-88324172; Email: Zgli@yahoo.cn

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233099
      • Recruiting
      • The First Affiliated Hospital of Bengbu Medical College
      • Contact: Changhao Xie
    • Hefei, Anhui, China, 230022
      • Not yet recruiting
      • The First Affiliated Hospital of Anhui Medical University
      • Contact: Zongwen Shuai
  • Beijing
    • Beijing, Beijing, China, 100029
      • Not yet recruiting
      • China-Japan Friendship Hospital
      • Contact: GuoChun Wang
    • Beijing, Beijing, China, 100050
      • Recruiting
      • Beijing Friendship Hospital, Capital Medical University
      • Contact: Yanying Liu
    • Beijing, Beijing, China, 100000
      • Recruiting
      • Peking University People's Hospital
      • Contact: Zhanguo Li
  • Fujian
    • Xiamen, Fujian, China, 361009
      • Not yet recruiting
      • The First Affiliated Hospital of Xiamen University
      • Contact: Guixiu Shi
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • The First Affiliated Hospital,Sun Yat-sen University
      • Contact: Niansheng Yang
    • Shenzhen, Guangdong, China, 518107
      • Recruiting
      • The Seventh Affiliated Hospital, Sun Yat-sen University
      • Contact: Ruojie Gu
  • Guangxi Zhuang Autonomous Region
    • Guilin, Guangxi Zhuang Autonomous Region, China, 541001
      • Recruiting
      • Affiliated Hospital of Guilin Medical University
      • Contact: Hanyou Mo
  • Hebei
    • Baoding, Hebei, China, 071030
      • Not yet recruiting
      • Affiliated Hospital of Hebei University
      • Contact: Minghua Xu
    • Shijiazhuang, Hebei, China, 050051
      • Not yet recruiting
      • Hebei People's Hospital
      • Contact: Fang Li
  • Heilongjiang
    • Daqing, Heilongjiang, China, Contact: Junsong Li
      • Not yet recruiting
      • Daqing Oilfield General hospital
      • Contact: Junsong Li
    • Qiqihar, Heilongjiang, China, 161005
      • Not yet recruiting
      • The First Hospital of Qiqihar
      • Contact: Wei Zhong
  • Henan
    • Luoyang, Henan, China, 471003
      • Not yet recruiting
      • The First Affiliated Hospital of Henan University of Science and Technology
      • Contact: Xiaofei Shi
    • Zhengzhou, Henan, China, 450052
      • Not yet recruiting
      • First Affiliated Hospital of Zhengzhou University
      • Contact: Shengyun Liu
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Anbin Huang
  • Hunan
    • Changsha, Hunan, China, 410000
      • Not yet recruiting
      • The Second Xiangya Hospital Of Central South University
      • Contact: Jing Tian
    • Yiyang, Hunan, China, 413000
      • Not yet recruiting
      • Yiyang Central Hospital
      • Contact: Jian Shi
    • Zhuzhou, Hunan, China, 412000
      • Not yet recruiting
      • ZhuZhou Central Hospital
      • Contact: Zhenhua Wen
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221000
      • Not yet recruiting
      • Xuzhou Central Hospital
      • Contact: Lin Liu
  • Jiangxi
    • Jiujiang, Jiangxi, China, 332000
      • Not yet recruiting
      • Jiujiang No.1 People's Hospital
      • Contact: Ju Liu
    • Nanchang, Jiangxi, China, 330006
      • Not yet recruiting
      • The First Affiliated Hospital Of Nanchang University
      • Contact: RUI WU
  • Jilin
    • Changchun, Jilin, China, 130021
      • Recruiting
      • Jilin Provincial People's Hospital
      • Contact: Lin Chen
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Not yet recruiting
      • Shengjing Hospital of China Medical University
      • Contact: Xiaofei Wang
  • Nei Monggol Autonomous Region
    • Hohhot, Nei Monggol Autonomous Region, China, 010000
      • Not yet recruiting
      • Affiliated Hospital of Inner Mongolia Medical University
      • Contact: Hongbin Li
  • Shandong
    • Binzhou, Shandong, China, 256699
      • Recruiting
      • Affiliated Hospital of Binzhou Medical College
      • Contact: Xuebin Wang
    • Jining, Shandong, China, 272002
      • Recruiting
      • Jining First People's Hospital
      • Contact: Jianhong Zhao
    • Linyi, Shandong, China, 276034
      • Recruiting
      • Linyi People's Hospital
      • Contact: Zunzhong Li
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Changhai Hospital of Shanghai
      • Contact: Jie Gao
    • Shanghai, Shanghai, China, 200000
      • Not yet recruiting
      • Renji Hospital, Shanghai Jiao Tong University School of Medicine
      • Contact: Sheng Chen
  • Shanxi
    • Taiyuan, Shanxi, China, 030001
      • Not yet recruiting
      • The Second Hospital of Shanxi Medical University
      • Contact: Xiaoxia Wang
    • Taiyuan, Shanxi, China, 030001
      • Not yet recruiting
      • The First Hospital of Shanxi Medical University
      • Contact: Zili Fu
    • Xi'an, Shanxi, China, 710061
      • Not yet recruiting
      • The First Affiliated Hospital of Xi 'an Jiaotong University
      • Contact: Lan He
  • Tianjin
    • Tianjin, Tianjin, China, 300000
      • Not yet recruiting
      • Tianjin Medical University General Hospital
      • Contact: Wei Wei
  • Xinjiang
    • Ürümqi, Xinjiang, China, 830000
      • Not yet recruiting
      • Xinjiang Uygur Autonomous Region People's Hospital
      • Contact: Lijun Wu
  • Zhejiang
    • Huzhou, Zhejiang, China, 313002
      • Not yet recruiting
      • The Third People's Hospital of Huzhou
      • Contact: Xiaobing Yang
    • Ningbo, Zhejiang, China, 315010
      • Recruiting
      • The First Hospital of Ningbo
      • Contact: Wen Qin
    • Wenling, Zhejiang, China, 317500
      • Recruiting
      • The First People's Hospital of Wenling
      • Contact: Yongjun Cheng
    • Wenzhou, Zhejiang, China, 325099
      • Recruiting
      • Wenzhou People's Hospital
      • Contact: Suxian Lin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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).
2. Males or females aged≥18 and ≤75 years.
3. 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.
4. SLEDAI-2K≥8 at screening.
5. 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.
6. Have a positive test for anti-dsDNA antibody (> normal range) and/or anti-nuclear antibody (ANA) and/or anti-Smith antibody at screening.
7. 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.

Exclusion Criteria:

Medical conditions:

1. Pregnant or lactating women, and men or women who have birth plans in the past 12 months.
2. 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.
3. Have severe lupus nephritis, or have required hemodialysis or high-dose glucocorticoid within 90 days prior to the first dose.
4. Have autoimmune diseases other than SLE (excluding secondary Sjogren's syndrome).
5. 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.
6. Have a history of or current diagnosis of Central Nervous System (CNS) diseases.
7. Have clinically documented cardiovascular diseases that are obviously unstable or not effectively treated.
8. Have significant active lung diseases (e.g., interstitial lung disease, obstructive pulmonary disease).
9. Have severe hepatobiliary diseases.
10. Have a history of malignant neoplasm.
11. Have a history of a major organ transplant or hematopoietic stem cell/marrow transplant.

12. Have known allergies to any component of the investigational agent as described in the Protocol.

    Concomitant medication and surgery:

13. Have received rituximab, epratuzumab, or any other B cell-depleting therapy within 12 months prior to randomization.
14. Have received cyclophosphamide and chlorambucil within 6 months prior to randomization.

15. 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:

16. Have a positive test for human immunodeficiency virus (HIV) antibody.
17. 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).

18. 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:

19. Have other conditions that are not appropriate for participation in the trial as considered by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Orelabrutinib Placebo; Subjects will be administered with Orelabrutinib Placebo orally once daily in combination with SOC therapy
Experimental: Orelabrutinib Lower Dose	Drug: Orelabrutinib (Low Dose); Subjects will be administered with lower dose of Orelabrutinib orally once daily in combination with SOC therapy
Experimental: Orelabrutinib Higher Dose	Drug: Orelabrutinib (High Dose); Subjects will be administered with higher dose of Orelabrutinib orally once daily in combination with SOC therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SLE Responder Index (SRI) - 4 response rate	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.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SLE Responder Index (SRI) - 6 response rate	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.	Week 48
British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response rate	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.	Week 48
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
Treatment Emergent Adverse Events, Treatment Related Adverse Events, Treatment Emergent Serious Adverse Events, Treatment Related Serious Adverse Events.		Up to Week 52
Changes from baseline in the levels of complement C3, complement C4, and anti-dsDNA antibody	Adopt the unified unit standard of central laboratory testing	Week 48
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

Collaborators and Investigators

• Sponsor: Beijing InnoCare Pharma Tech Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2023
• Primary Completion (Estimated): May 30, 2024
• Study Completion (Estimated): May 30, 2025

Study Registration Dates

• First Submitted: January 10, 2023
• First Submitted That Met QC Criteria: January 17, 2023
• First Posted (Actual): January 18, 2023

Study Record Updates

• Last Update Posted (Actual): June 5, 2023
• Last Update Submitted That Met QC Criteria: June 2, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: ICP-CL-00124

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No