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Daratumumab in Treatment of PGNMID and C3 GN

Primary Purpose

Membranoproliferative Glomerulonephritis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Daratumumab
Sponsored by
Fernando Fervenza
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Membranoproliferative Glomerulonephritis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Daratumumab

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
March 20, 2017
Last Updated
August 26, 2022
Sponsor
Fernando Fervenza
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1. Study Identification

Unique Protocol Identification Number
NCT03095118
Brief Title
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

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
September 7, 2017 (Actual)
Primary Completion Date
October 14, 2019 (Actual)
Study Completion Date
May 12, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Fernando Fervenza

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Membranoproliferative Glomerulonephritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Daratumumab
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Daratumumab
Other Intervention Name(s)
Darzalex
Intervention Description
Intravenously (IV) at a dose of 16 mg/kg once weekly for 8 weeks, followed by once every 2 weeks for eight additional doses
Primary Outcome Measure Information:
Title
Number of Treatment-Emergent Adverse Events
Description
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
Secondary Outcome Measure Information:
Title
Remission Status at 6 Months
Description
The number of subjects to reach either complete remission or partial remission at 6 months after infusion.
Time Frame
6 months
Title
Remission Status at 12 Months
Description
The number of subjects to reach either complete remission or partial remission at 12 months after infusion.
Time Frame
12 months
Title
Proteinuria at Baseline
Description
Measured using 24 hour urine collection reported in mg/24h
Time Frame
Baseline
Title
Proteinuria at 6 Months
Description
Measured using 24 hour urine collection reported in mg/24 h
Time Frame
6 months
Title
Proteinuria at 12 Months
Description
Measured using 24 hour urine collection reported in mg/24h
Time Frame
12 months
Title
Serum Creatinine at Baseline
Description
Blood serum collected and reported in mg/dL
Time Frame
Baseline
Title
Serum Creatinine at 6 Months
Description
Blood serum collected and reported in mg/dL
Time Frame
6 months
Title
Serum Creatinine at 12 Months
Description
Blood serum collected and reported in mg/dL
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fernando C Fervenza, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
33685975
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.
Results Reference
derived
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials

Learn more about this trial

Daratumumab in Treatment of PGNMID and C3 GN

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