Zanubrutinib in Participants With Active Proliferative Lupus Nephritis

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Lupus Nephritis

Intervention / Treatment
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* Drug: Zanubrutinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Clinical diagnosis of SLE according to the Systemic Lupus International Collaborating Clinics 2012 criteria. 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. Positive antinuclear antibodies, positive anti-dsDNA autoantibody, and/or positive anti Smith autoantibody at screening Has 24-hour urine protein excretion > 1.0 g at screening. Key Exclusion Criteria: Exclusion criteria related to systemic lupus erythematous and other diseases: Glomerulonephritis caused by reasons other than systemic lupus erythematous. Sclerosis in >50% of glomeruli on renal biopsy. Any other inflammatory diseases that might confound the assessments of efficacy, including but not limited to rheumatoid arthritis, myositis, vasculitis, or overlapping syndrome. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |