Clinical trial NCT03095118: Daratumumab in Treatment of PGNMID and C3 GN
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Membranoproliferative Glomerulonephritis
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
First posted: 2017-03-29
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Treatment-Emergent Adverse Events
timeFrame: 1 year
Secondary outcomes:
measure: Remission Status at 6 Months
timeFrame: 6 months
measure: Remission Status at 12 Months
timeFrame: 12 months
measure: Proteinuria at Baseline
timeFrame: Baseline
measure: Proteinuria at 6 Months
timeFrame: 6 months
measure: Proteinuria at 12 Months
timeFrame: 12 months
measure: Serum Creatinine at Baseline
timeFrame: Baseline
measure: Serum Creatinine at 6 Months
timeFrame: 6 months
measure: Serum Creatinine at 12 Months
timeFrame: 12 months
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Fernando C Fervenza, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zand L, Rajkumar SV, Leung N, Sethi S, El Ters M, Fervenza FC. Safety and Efficacy of Daratumumab in Patients with Proliferative GN with Monoclonal Immunoglobulin Deposits. J Am Soc Nephrol. 2021 May 3;32(5):1163-1173. doi: 10.1681/ASN.2020101541. Epub 2021 Mar 8.