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Zanubrutinib in Participants With Active Proliferative Lupus Nephritis

Phase 2
Completed
Conditions
Lupus Nephritis
Interventions
Drug: Placebo
Registration Number
NCT04643470
Lead Sponsor
BeiGene
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
177
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboParticipants will receive placebo to match zanubrutinib for 72 weeks
Zanubrutinib Low DoseZanubrutinibParticipants will receive zanubrutinib 40 mg twice daily (BID) for 72 weeks
Zanubrutinib Medium DoseZanubrutinibParticipants will receive zanubrutinib 160 mg once daily (QD) for 72 weeks
Zanubrutinib High DoseZanubrutinibParticipants will receive zanubrutinib 160 mg twice daily (BID) for 72 weeks
Primary Outcome Measures
NameTimeMethod
Proportion of participants with complete renal responseWeek 49 Day 1
Secondary Outcome Measures
NameTimeMethod
Proportion of participants achieving complete renal responseUp to Week 73 Day 1
Proportion of participants achieving overall renal responseUp to Week 73 Day 1
Time to first overall renal responseUp to Week 73 Day 1

The time from the date of randomization to the date of the first overall renal response

Proportion of participants achieving partial renal responseUp to Week 73 Day 1
Time to first complete renal responseUp to Week 73 Day 1

The time from the date of randomization to the date of the first complete renal response

Change in total Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scoreBaseline to Week 49 Day 1

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

Area under plasma concentration time curve (AUC) of zanubrutinibWeek 1 Day 1 and Week 5 Day 1

Trial Locations

Locations (44)

Sun Yat Sen Memorial Hospital, Sun Yat Sen University (North)

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Guangzhou, Guangdong, China

Jiangsu Province Hospital

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Nanjing, Jiangsu, China

Shengjing Hospital of China Medical University

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Shenyang, Liaoning, China

The Third Affiliated Hospital, Sun Yat Sen University

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Guangzhou, Guangdong, China

Guangdong Province Traditional Chinese Medical Hospitsal

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Guangzhou, Guangdong, China

Shanghai General Hospital

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Shanghai, Shanghai, China

The First Affiliated Hospital of Xinjiang Medical University

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Urumqi, Xinjiang, China

Anhui Provincial Hospital

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Hefei, Anhui, China

Peking University Peoples Hospital

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Beijing, Beijing, China

Guizhou Provincial Peoples Hospital

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Guiyang, Guizhou, China

Peking University International Hospital

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Beijing, Beijing, China

The First Affiliated Hospital of Xiamen University

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Xiamen, Fujian, China

Zhongshan Hospital Xiamen University

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Xiamen, Fujian, China

Guangdong Provincial Peoples Hospital

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Guangzhou, Guangdong, China

The First Affiliated Hospital, Sun Yat Sen University

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Guangzhou, Guangdong, China

Jiangmen Central Hospital

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Jiangmen, Guangdong, China

Peking University Shenzhen Hospital

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Shenzhen, Guangdong, China

The Second Peoples Hospital of Shenzhen

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Shenzhen, Guangdong, China

Liuzhou Workers Hospital

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Liuzhou, Guangxi, China

The Peoples Hospital of Guangxi Zhuang Autonomous Region

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Nanning, Guangxi, China

The First Affiliated Hospital of Zhengzhou University

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Zhengzhou, Henan, China

Hainan General Hospital

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Haikou, Hainan, China

Renmin Hospital of Wuhan University

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Wuhan, Hubei, China

The Second Xiangya Hospital of Central South University

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Changsha, Hunan, China

General Hospital of Eastern Theater Command

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Nanjing, Jiangsu, China

Wuxi Peoples Hospital

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Wuxi, Jiangsu, China

The First Affiliated Hospital of Nanchang University Branch Donghu

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Nanchang, Jiangxi, China

The Affiliated Hospital of Xuzhou Medical University

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Xuzhou, Jiangsu, China

The Second Affiliated Hospital of Nanchang University

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Nanchang, Jiangxi, China

The Second Hospital of Jilin University

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Changchun, Jilin, China

First Affiliated Hospital of Dalian Medical University

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Dalian, Liaoning, China

General Hospital of Ningxia Medical University

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Yinchuan, Ningxia, China

Second Hospital of Shanxi Medical University

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Taiyuan, Shanxi, China

The Second Affiliated Hospital of Xian Jiaotong University

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Xian, Shaanxi, China

The First Affiliated Hospital of Xian Jiaotong University

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Xian, Shaanxi, China

Shandong Provincial Hospital

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Jinan, Shandong, China

The Affiliated Hospital of Qingdao University Branch South

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Qingdao, Shandong, China

Huashan Hospital Affiliated to Fudan University

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Shanghai, Shanghai, China

West China Hospital, Sichuan University

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Chengdu, Sichuan, China

Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital

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Chengdu, Sichuan, China

The Second Affiliated Hospital of Tianjin Medical University

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Tianjin, Tianjin, China

First Affiliated Hospital of Kunming Medical University

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Kunming, Yunnan, China

The First Affiliated Hospital, Zhejiang University School of Medicine

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Hangzhou, Zhejiang, China

Ningbo First Hospital

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Ningbo, Zhejiang, China

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