Membranoproliferative Glomerulonephritis
Conditions
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.
Interventions
DRUGDaratumumab
Intravenously (IV) at a dose of 16 mg/kg once weekly for 8 weeks, followed by once every 2 weeks for eight additional doses
Sponsors
Fernando Fervenza
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment-Emergent Adverse Events | 1 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Remission Status at 12 Months | 12 months | The number of subjects to reach either complete remission or partial remission at 12 months after infusion. |
| Proteinuria at Baseline | Baseline | Measured using 24 hour urine collection reported in mg/24h |
| Proteinuria at 6 Months | 6 months | Measured using 24 hour urine collection reported in mg/24 h |
| Remission Status at 6 Months | 6 months | The number of subjects to reach either complete remission or partial remission at 6 months after infusion. |
| Serum Creatinine at Baseline | Baseline | Blood serum collected and reported in mg/dL |
| Serum Creatinine at 6 Months | 6 months | Blood serum collected and reported in mg/dL |
| Serum Creatinine at 12 Months | 12 months | Blood serum collected and reported in mg/dL |
| Proteinuria at 12 Months | 12 months | Measured using 24 hour urine collection reported in mg/24h |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Daratumumab 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
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 | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Diagnosis not associated with monoclonal gammopathy | 1 |
Baseline characteristics
| Characteristic | Daratumumab |
|---|---|
| Age, Continuous | 51.3 years STANDARD_DEVIATION 20.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 3 / 12 |
Outcome results
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.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daratumumab | Number of Treatment-Emergent Adverse Events | 5 Serious Adverse Events |
Secondary
Proteinuria at 12 Months
Measured using 24 hour urine collection reported in mg/24h
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daratumumab | Proteinuria at 12 Months | 1264 mg/24h |
Comparison: Proteinuria baseline values compared to 12 month follow up valuesp-value: 0.004t-test, 2 sided
Secondary
Proteinuria at 6 Months
Measured using 24 hour urine collection reported in mg/24 h
Time frame: 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daratumumab | Proteinuria at 6 Months | 702 mg/24h |
Comparison: Proteinuria baseline values compared to 6 month follow up valuesp-value: 0.001t-test, 2 sided
Secondary
Proteinuria at Baseline
Measured using 24 hour urine collection reported in mg/24h
Time frame: Baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Daratumumab | Proteinuria at Baseline | 4346 mg/24h |
Secondary
Remission Status at 12 Months
The number of subjects to reach either complete remission or partial remission at 12 months after infusion.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Daratumumab | Remission Status at 12 Months | 9 Participants |
Secondary
Remission Status at 6 Months
The number of subjects to reach either complete remission or partial remission at 6 months after infusion.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Daratumumab | Remission Status at 6 Months | 8 Participants |
Secondary
Serum Creatinine at 12 Months
Blood serum collected and reported in mg/dL
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Daratumumab | Serum Creatinine at 12 Months | 1.25 mg/dL | Standard Deviation 0.52 |
Comparison: Serum creatinine baseline values comparted to 12 month follow up valuesp-value: 0.16t-test, 2 sided
Secondary
Serum Creatinine at 6 Months
Blood serum collected and reported in mg/dL
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Daratumumab | Serum Creatinine at 6 Months | 1.25 mg/dL | Standard Deviation 0.44 |
Comparison: Serum creatinine baseline values compared to 6 month follow up valuesp-value: 0.15t-test, 2 sided
Secondary
Serum Creatinine at Baseline
Blood serum collected and reported in mg/dL
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Daratumumab | Serum Creatinine at Baseline | 1.36 mg/dL | Standard Deviation 0.57 |