Zanubrutinib in Participants With Active Proliferative Lupus Nephritis

A Phase 2, Multicenter, Randomized, Double Blind, Placebo Controlled Study to Evaluate the Safety and Efficacy of Zanubrutinib in Patients With Active Proliferative Lupus Nephritis

The primary objective of this study is to evaluate the efficacy of zanubrutinib added to standard of care as measured by complete renal response for participants with active proliferative lupus nephritis

Study Overview

• Status: Completed
• Conditions: Lupus Nephritis
• Intervention / Treatment: Drug: Zanubrutinib; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 177
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230000
      • Anhui Provincial Hospital
  • Beijing
    • Beijing, Beijing, China, 102206
      • Peking University International Hospital
    • Beijing, Beijing, China, 100044
      • Peking University Peoples Hospital
  • Fujian
    • Xiamen, Fujian, China, 361003
      • The First Affiliated Hospital of Xiamen University
    • Xiamen, Fujian, China, 361004
      • Zhongshan Hospital Xiamen University
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial Peoples Hospital
    • Guangzhou, Guangdong, China, 510000
      • Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North)
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital, Sun Yat Sen University
    • Guangzhou, Guangdong, China, 510655
      • Guangdong Province Traditional Chinese Medical Hospitsal
    • Guangzhou, Guangdong, China, 510630
      • The Third Affiliated Hospital, Sun Yat Sen University
    • Jiangmen, Guangdong, China, 529030
      • Jiangmen Central Hospital
    • Shenzhen, Guangdong, China, 518036
      • Peking University Shenzhen Hospital
    • Shenzhen, Guangdong, China, 518037
      • The Second Peoples Hospital of Shenzhen
  • Guangxi
    • Liuzhou, Guangxi, China, 545005
      • Liuzhou Workers Hospital
    • Nanning, Guangxi, China, 530021
      • The Peoples Hospital of Guangxi Zhuang Autonomous Region
  • Guizhou
    • Guiyang, Guizhou, China, 550002
      • Guizhou Provincial Peoples Hospital
  • Hainan
    • Haikou, Hainan, China, 570206
      • Hainan General Hospital
  • Henan
    • Zhengzhou, Henan, China, 450052
      • The First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China, 430060
      • Renmin Hospital of Wuhan University
  • Hunan
    • Changsha, Hunan, China, 410011
      • The Second Xiangya Hospital of Central South University
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province Hospital
    • Nanjing, Jiangsu, China, 210002
      • General Hospital of Eastern Theater Command
    • Wuxi, Jiangsu, China, 214023
      • Wuxi Peoples Hospital
    • Xuzhou, Jiangsu, China, 221000
      • The Affiliated Hospital of Xuzhou Medical University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The Second Affiliated Hospital of Nanchang University
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University Branch Donghu
  • Jilin
    • Changchun, Jilin, China, 130022
      • The Second Hospital of Jilin University
  • Liaoning
    • Dalian, Liaoning, China, 116011
      • First Affiliated Hospital of Dalian Medical University
    • Shenyang, Liaoning, China, 110004
      • Shengjing Hospital Of China Medical University
  • Ningxia
    • Yinchuan, Ningxia, China, 750004
      • General Hospital of Ningxia Medical University
  • Shaanxi
    • Xian, Shaanxi, China, 710061
      • The First Affiliated Hospital of Xian Jiaotong University
    • Xian, Shaanxi, China, 710004
      • The Second Affiliated Hospital of Xian Jiaotong University
  • Shandong
    • Jinan, Shandong, China, 250021
      • Shandong Provincial Hospital
    • Qingdao, Shandong, China, 266000
      • The Affiliated Hospital of Qingdao University Branch South
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Shanghai General Hospital
    • Shanghai, Shanghai, China, 200040
      • Huashan Hospital Affiliated to Fudan University
  • Shanxi
    • Taiyuan, Shanxi, China, 030001
      • Second Hospital of Shanxi Medical University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
    • Chengdu, Sichuan, China, 610071
      • Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300000
      • The Second Affiliated Hospital of Tianjin Medical University
  • Xinjiang
    • Urumqi, Xinjiang, China, 830054
      • The First Affiliated Hospital of Xinjiang Medical University
  • Yunnan
    • Kunming, Yunnan, China, 650032
      • First Affiliated Hospital of Kunming Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, Zhejiang University School of Medicine
    • Ningbo, Zhejiang, China, 315010
      • Ningbo First Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Clinical diagnosis of SLE according to the Systemic Lupus International Collaborating Clinics 2012 criteria.
2. ISN/RPS 2003 Class III/IV lupus nephritis [Type III(A), III (A+C), IV (A), and IV (A+C)], with or without Class V, as confirmed by a renal biopsy.
3. Positive antinuclear antibodies, positive anti-dsDNA autoantibody, and/or positive anti Smith autoantibody at screening
4. Has 24-hour urine protein excretion > 1.0 g at screening.

Key Exclusion Criteria:

Exclusion criteria related to systemic lupus erythematous and other diseases:

1. Glomerulonephritis caused by reasons other than systemic lupus erythematous.
2. Sclerosis in >50% of glomeruli on renal biopsy.
3. Any other inflammatory diseases that might confound the assessments of efficacy, including but not limited to rheumatoid arthritis, myositis, vasculitis, or overlapping syndrome.
4. Severe extrarenal SLE, including but not limited to severe pulmonary arterial hypertension, severe myocarditis, severe central nervous system lupus (such as neuropsychiatric SLE, seizures, psychosis, transverse myelitis, central nervous system vasculitis and optic neuritis), etc.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zanubrutinib Low Dose; Participants will receive zanubrutinib 40 mg twice daily (BID) for 72 weeks	Drug: Zanubrutinib; Administered as specified in the treatment arm; Other Names: Brukinsa; BGB-3111
Experimental: Zanubrutinib High Dose; Participants will receive zanubrutinib 160 mg twice daily (BID) for 72 weeks	Drug: Zanubrutinib; Administered as specified in the treatment arm; Other Names: Brukinsa; BGB-3111
Experimental: Zanubrutinib Medium Dose; Participants will receive zanubrutinib 160 mg once daily (QD) for 72 weeks	Drug: Zanubrutinib; Administered as specified in the treatment arm; Other Names: Brukinsa; BGB-3111
Experimental: Placebo; Participants will receive placebo to match zanubrutinib for 72 weeks	Drug: Placebo; Placebo to match zanubrutinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of participants with complete renal response	Week 49 Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants achieving complete renal response		Up to Week 73 Day 1
Proportion of participants achieving partial renal response		Up to Week 73 Day 1
Proportion of participants achieving overall renal response		Up to Week 73 Day 1
Time to first complete renal response	The time from the date of randomization to the date of the first complete renal response	Up to Week 73 Day 1
Time to first overall renal response	The time from the date of randomization to the date of the first overall renal response	Up to Week 73 Day 1
Change in total Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score	SLEDAI-2K score is a systemic lupus erythematosus (SLE) activity index based on the presence of 24 features in 9 organ systems which ranges from 0 - 105, with higher scores indicating more severe features in participants in the past 30 days	Baseline to Week 49 Day 1
Area under plasma concentration time curve (AUC) of zanubrutinib		Week 1 Day 1 and Week 5 Day 1

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Zhen Yao, MD, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2020
• Primary Completion (Actual): February 26, 2024
• Study Completion (Actual): August 26, 2024

Study Registration Dates

• First Submitted: November 18, 2020
• First Submitted That Met QC Criteria: November 19, 2020
• First Posted (Actual): November 25, 2020

Study Record Updates

• Last Update Posted (Actual): November 29, 2024
• Last Update Submitted That Met QC Criteria: November 27, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Lupus Nephritis; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Zanubrutinib
• Other Study ID Numbers: BGB-3111-217; CTR20202662 (Other Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes