Daratumumab in Treatment of PGNMID and C3 GN

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Membranoproliferative Glomerulonephritis

Intervention / Treatment
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* Drug: Daratumumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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: Daratumumab<br>Subjects will receive daratumumab intravenously at a dose of 16 mg/kg once weekly for 8 weeks followed by once every 2 weeks for 8 additional doses | Drug: Daratumumab<br>* Intravenously (IV) at a dose of 16 mg/kg once weekly for 8 weeks, followed by once every 2 weeks for eight additional doses<br>* Other names: Darzalex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission Status at 6 Months | The number of subjects to reach either complete remission or partial remission at 6 months after infusion. | 6 months | 
| Remission Status at 12 Months | The number of subjects to reach either complete remission or partial remission at 12 months after infusion. | 12 months | 
| Proteinuria at Baseline | Measured using 24 hour urine collection reported in mg/24h | Baseline | 
| Proteinuria at 6 Months | Measured using 24 hour urine collection reported in mg/24 h | 6 months | 
| Proteinuria at 12 Months | Measured using 24 hour urine collection reported in mg/24h | 12 months | 
| Serum Creatinine at Baseline | Blood serum collected and reported in mg/dL | Baseline | 
| Serum Creatinine at 6 Months | Blood serum collected and reported in mg/dL | 6 months | 
| Serum Creatinine at 12 Months | Blood serum collected and reported in mg/dL | 12 months |