Clinical trial NCT05688696: Evaluate the Efficacy and Safety of Orelabrutinib in Adult Patients With Systemic Lupus Erythematosus
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus, SLE
Lead sponsor: Beijing InnoCare Pharma Tech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-01-18
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: SLE Responder Index (SRI) - 4 response rate
timeFrame: Week 48
Secondary outcomes:
measure: SLE Responder Index (SRI) - 6 response rate
timeFrame: Week 48
measure: British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response rate
timeFrame: Week 48
measure: Time to 1st flare
timeFrame: Week 48
measure: The proportion of subjects whose average prednisone dose has been reduced by≥25% from baseline to ≤7.5 mg/day
timeFrame: Week 48
measure: Changes from baseline in the levels of complement C3, complement C4, and anti-dsDNA antibody
timeFrame: Week 48
measure: Treatment Emergent Adverse Events, Treatment Related Adverse Events, Treatment Emergent Serious Adverse Events, Treatment Related Serious Adverse Events.
timeFrame: Up to Week 52
measure: 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. )
timeFrame: Week 48
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The first affiliated hospital of bengbu medical college
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Beijing
country: China
facility: China-Japan Friendship Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
state: Beijing
city: Xiamen
country: China
facility: The First Affiliated Hospital of XiaMen University
state: Fujian
city: Guangzhou
country: China
facility: The First Affiliated Hospital,Sun Yat-sen University
state: Guangdong
city: Shantou
country: China
facility: The first affiliated hospital of shantou university medical college
state: Guangdong
city: Shenzhen
country: China
facility: The Seventh Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Guilin
country: China
facility: Affiliated Hospital of Guilin Medical University
state: Guangxi Zhuang Autonomous Region
city: Baoding
country: China
facility: Affiliated Hospital of HeBei University
state: Hebei
city: Shijiazhuang
country: China
facility: Hebei People's Hospital
state: Hebei
city: Daqing
country: China
facility: Daqing Oilfield General Hospital
state: Heilongjiang
city: Qiqihar
country: China
facility: The first hospital of Qiqihar
state: Heilongjiang
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Zhengzhou
country: China
facility: First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: The Second XIANGYA Hospital Of Central South University
state: Hunan
city: Yiyang
country: China
facility: Yiyang Central Hospital
state: Hunan
city: Zhuzhou
country: China
facility: Zhuzhou Central Hospital
state: Hunan
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
state: Jiangsu
city: Jiujiang
country: China
facility: Jiujiang NO.1 People's Hospital
state: Jiangxi
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: Jilin Provincial People's Hospital
state: Jilin
city: Shenyang
country: China
facility: Shengjing Hospital of china medical university
state: Liaoning
city: Hohhot
country: China
facility: Affiliated Hospital of Inner Mongolia Medical University
state: Nei Monggol Autonomous Region
city: Binzhou
country: China
facility: Affiliated Hospital of Binzhou Medical College
state: Shandong
city: Jining
country: China
facility: Jining First People's Hospital
state: Shandong
city: Linyi
country: China
facility: Linyi People's Hospital
state: Shandong
city: Shanghai
country: China
facility: Changhai Hospital of Shanghai
state: Shanghai
city: Shanghai
country: China
facility: Renji Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Taiyuan
country: China
facility: The First Hospital of Shanxi Medical University
state: Shanxi
city: Taiyuan
country: China
facility: The Second Hospital of Shanxi Medical University
state: Shanxi
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi 'an Jiaotong University
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Ürümqi
country: China
facility: Xinjiang Uygur Autonomous Region People's Hospital
state: Xinjiang
city: Huzhou
country: China
facility: The Third People's Hospital of Huzhou
state: Zhejiang
city: Ningbo
country: China
facility: The First Hospital of Ningbo
state: Zhejiang
city: Wenling
country: China
facility: The First People's Hospital of Wenling
state: Zhejiang
city: Wenzhou
country: China
facility: Wenzhou People's Hospital
state: Zhejiang
Study officials:
References: