Bortezomib for Treating Glomerular Diseases

Study Overview
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Brief Summary
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Bortezomib is a proteasome inhibitor that inhibits autoantibody production, and reduces podocyte damage and mesangial hyperplasia caused by NF-κB activation in the kidney. Literature has reported that bortezomib can achieve a complete response rate of up to 38% in the treatment of glomerular diseases, but its safety and effectiveness remain to be assessed for the Chinese demographic. This study attempts to explore a new treatment plan for glomerular disease by observing the therapeutic effect of bortezomib on glomerular disease.

Official Title
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Prospective Observation of Bortezomib in the Treatment of Glomerular Diseases

Conditions
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Bortezomib, Glomerulonephritis, MN, MPGN, FSGS, IgA Nephropathy

Intervention / Treatment
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* Drug: Bortezomib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Glomerular diseases confirmed by renal biopsy (including IgA nephropathy, membranous nephropathy, FSGS, etc.) Aged 18-65, male or female Signed informed consent 24h proteinuria >1.5g/24h Glomerular filtration rate (eGFR) >30ml/min/1.73m2 (calculated according to CKD-EPI formula) within 14 days before enrollment. Blood pressure <140/90mmHg after drug treatment Unless there are contraindications, subjects must take a steady dose of ACEI and/or ARB for at least 4 weeks before screening Exclusion Criteria: Renal pathology: glomerulosclerosis ratio >70%, interstitial fibrosis > severe Received immunosuppressant treatment within the past 6 months Inability to tolerate bortezomib Platelet count < 30×109/L within 14 days before enrollment Neutrophil count < 1.0×109/L within 14 days before enrollment Subjects had >grade 2 peripheral neuropathy within 14 days before enrollment ECG evidence of myocardial infarction or NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmia, or acute ischemia or active conduction system abnormalities within 6 months before enrollment Abnormal liver function such as alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >=3 times normal upper limit (ULN), total bilirubin >= 2 times ULN Newly diagnosed malignant tumor (within 5 years) or undergoing radiotherapy/chemotherapy Women who are pregnant or breast-feeding, or women of childbearing age who cannot guarantee effective contraception New serious life-threatening infections Active infectious diseases such as active tuberculosis, active viral hepatitis, HIV infection. Mental disorders and psychotropic drug uses Patients with an estimated life expectancy of fewer than 12 months Patients that were difficult to follow up on or had poor compliance Patients who do not wish to sign the form of informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glomerular disease patients<br> | Drug: Bortezomib<br>* Dexamethasone 10mg+ bortezomib (1.3mg /m2 IV) was administered at D1,D4,D8,D11, one month for 1 cycle, for 2 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission Rate of Proteinuria | 24h Proteinuria <300mg/24h | One Year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of Bortezomib | Incidence of Treatment-Emergent Adverse Events | One Year |