Daratumumab in Treatment of PGNMID and C3 GN

August 26, 2022 updated by: Fernando Fervenza

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

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.

Study Overview

Status

Completed

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Intravenously (IV) at a dose of 16 mg/kg once weekly for 8 weeks, followed by once every 2 weeks for eight additional doses
Other Names:
  • Darzalex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Treatment-Emergent Adverse Events
Time Frame: 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.
1 year

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Fernando C Fervenza, MD, Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 7, 2017

Primary Completion (Actual)

October 14, 2019

Study Completion (Actual)

May 12, 2020

Study Registration Dates

First Submitted

March 20, 2017

First Submitted That Met QC Criteria

March 23, 2017

First Posted (Actual)

March 29, 2017

Study Record Updates

Last Update Posted (Actual)

August 31, 2022

Last Update Submitted That Met QC Criteria

August 26, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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