Daratumumab in Treatment of PGNMID and C3 GN

Membranoproliferative Glomerulonephritis Clinical Trial

Official title:

Single-center Phase 2 Open-label Trial Evaluating Efficacy and Safety of Daratumumab in Treatment of Patients With Proliferative Glomerulonephritis With Monoclonal Immune Deposits and C3 Glomerulopathy Associated With Monoclonal Gammopathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03095118
• Other study ID #: 16-004805
• Status: Completed
• Phase: Phase 2
• Start date: September 7, 2017
• Est. completion date: May 12, 2020

Study information

• Verified date: August 2022
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is being done to see if daratumumab is safe and effective in the treatment of proliferative glomerulonephritis with monoclonal immune deposits (PGNMID) and C3 glomerulopathy associated with monoclonal gammopathy (C3GN). This is an inflammatory disease in the kidney due to the production of abnormal proteins. There are no known standard effective treatments for patients with PGNMID and C3GN secondary to monoclonal gammopathy. These diseases are caused by abnormal production of proteins (monoclonals) by abnormal clones. Daratumamb has been shown to be effective in treating patients with multiple myeloma a disease which also caused by over production of monoclonal proteins from abnormal clones. Everyone in this study will receive daratumumab.

Description:

This study is an open-label phase 2 trial of the safety and efficacy of daratumumab, in the treatment of PGNMID and C3GN associated with monoclonal gammopathy. Subjects will be screened at outpatient Nephrology Clinic visit appointments and interested qualified subjects will be consented and offered participation in this trial. Once consent has been obtained baseline values will be established and subjects will begin treatment and follow-up for the next 12 months. Daratumumab will be administered once weekly for 8 weeks and then once every 2 weeks for 8 additional doses. Patients will be followed for a total of 12 months (6 months after the last infusion). A final visit for evaluation and collection of lab samples will be conducted at the end of the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: May 12, 2020
• Est. primary completion date: October 14, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years of age
• Renal biopsy read at Mayo Clinic confirming the diagnosis of PGNMID or C3 GN
• In cases of C3GN serum electrophoresis with immunofixation should confirm presence of monoclonal gammopathy
• Proteinuria = 1000 mg over 24 hours
• eGFR = 20 mL/min/SA
• Subjects able and willing to give informed consent

Exclusion Criteria:

• Pregnancy
• Hepatitis B or C, HIV
• Multiple myeloma
• Anemia with Hgb < 8.5 g/dL
• Thrombocytopenia with platelet count < 100,000
• Leukopenia with WBC < 3.5
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complication
• Unable to provide consent
• Patients receiving therapy with oral prednisone or glucocorticoid equivalent in the last 6 weeks
• Patients who had received immunosuppressive therapy including cyclophosphamide, MMF, cyclosporine, tacrolimus or azathioprine in the last 3 months
• Patients who received rituximab previously with CD20 count of zero at the time of enrollment

Related Conditions & MeSH terms

• Glomerulonephritis
• Glomerulonephritis, Membranoproliferative
• Membranoproliferative Glomerulonephritis

Intervention

Drug:
• Daratumumab
Intravenously (IV) at a dose of 16 mg/kg once weekly for 8 weeks, followed by once every 2 weeks for eight additional doses

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Fernando Fervenza

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Treatment-Emergent Adverse Events	Number of treatment-emergent adverse events as defined as major infection (defined as the development of pneumonia, severe urinary tract infection/pyelonephritis, sepsis, meningitis), grade 3 or 4 anemia, leukopenia, or thrombocytopenia.	1 year
Secondary	Remission Status at 6 Months	The number of subjects to reach either complete remission or partial remission at 6 months after infusion.	6 months
Secondary	Remission Status at 12 Months	The number of subjects to reach either complete remission or partial remission at 12 months after infusion.	12 months
Secondary	Proteinuria at Baseline	Measured using 24 hour urine collection reported in mg/24h	Baseline
Secondary	Proteinuria at 6 Months	Measured using 24 hour urine collection reported in mg/24 h	6 months
Secondary	Proteinuria at 12 Months	Measured using 24 hour urine collection reported in mg/24h	12 months
Secondary	Serum Creatinine at Baseline	Blood serum collected and reported in mg/dL	Baseline
Secondary	Serum Creatinine at 6 Months	Blood serum collected and reported in mg/dL	6 months
Secondary	Serum Creatinine at 12 Months	Blood serum collected and reported in mg/dL	12 months

External Links

•   Mayo Clinic Clinical Trials