Bortezomib for Treating Glomerular Diseases

Prospective Observation of Bortezomib in the Treatment of Glomerular Diseases

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.

Study Overview

• Status: Recruiting
• Conditions: Glomerulonephritis; IgA Nephropathy; FSGS; Bortezomib; MN; MPGN
• Intervention / Treatment: Drug: Bortezomib

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Recruiting
      • Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
      • Contact: Li Lin; Phone Number: 008602174370045; Email: sn2011linli@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 2, 2022
• Primary Completion (ANTICIPATED): December 31, 2023
• Study Completion (ANTICIPATED): December 31, 2023

Study Registration Dates

• First Submitted: May 10, 2022
• First Submitted That Met QC Criteria: May 19, 2022
• First Posted (ACTUAL): May 20, 2022

Study Record Updates

• Last Update Posted (ACTUAL): October 31, 2022
• Last Update Submitted That Met QC Criteria: October 28, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Glomerulonephritis, IGA; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: KY2022-53

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No