Daratumumab in Treatment of PGNMID and C3 GN

• Sponsor: Fernando Fervenza (Other)
• Overall Status: Completed
• CT.gov ID: NCT03095118
• Collaborator: (none)
• Enrollment: 12
• Location: 1
• Arm: 1
• Actual Duration (Months): 32.1
• Patients Per Site Per Month: 0.4

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Membranoproliferative Glomerulonephritis	Drug: Daratumumab	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Sep 7, 2017
• Actual Primary Completion Date: Oct 14, 2019
• Actual Study Completion Date: May 12, 2020

Arms and Interventions

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	Drug: 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; Other Names: Darzalex

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Remission Status at 6 Months [6 months]

   The number of subjects to reach either complete remission or partial remission at 6 months after infusion.

2. Remission Status at 12 Months [12 months]

   The number of subjects to reach either complete remission or partial remission at 12 months after infusion.

3. Proteinuria at Baseline [Baseline]

   Measured using 24 hour urine collection reported in mg/24h

4. Proteinuria at 6 Months [6 months]

   Measured using 24 hour urine collection reported in mg/24 h

5. Proteinuria at 12 Months [12 months]

   Measured using 24 hour urine collection reported in mg/24h

6. Serum Creatinine at Baseline [Baseline]

   Blood serum collected and reported in mg/dL

7. Serum Creatinine at 6 Months [6 months]

   Blood serum collected and reported in mg/dL

8. Serum Creatinine at 12 Months [12 months]

   Blood serum collected and reported in mg/dL

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Fernando Fervenza

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 18, 2019

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

None provided.

• Responsible Party: Fernando Fervenza, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT03095118
• Other Study ID Numbers: 16-004805
• First Posted: Mar 29, 2017
• Last Update Posted: Jul 16, 2021
• Last Verified: Jun 1, 2021

• 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
• Additional relevant MeSH terms: Glomerulonephritis; Glomerulonephritis, Membranoproliferative; Daratumumab

Study Results

Participant Flow

Arm/Group Title	Daratumumab
Arm/Group 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 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
Period Title: Overall Study
STARTED	12
COMPLETED	10
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Daratumumab
Arm/Group 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 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
Overall Participants	12
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.3 (20.6)
Sex: Female, Male (Count of Participants)
Female	7 58.3%
Male	5 41.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 8.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	11 91.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	12 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Daratumumab
Arm/Group 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 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
Measure Participants	12
Number [Serious Adverse Events]	5

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Daratumumab
Arm/Group 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 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
Measure Participants	10
Count of Participants [Participants]	8 66.7%

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Daratumumab
Arm/Group 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 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
Measure Participants	10
Count of Participants [Participants]	9 75%

4. Secondary Outcome

Title	Proteinuria at Baseline
Description	Measured using 24 hour urine collection reported in mg/24h
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Daratumumab
Arm/Group 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 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
Measure Participants	10
Median (Inter-Quartile Range) [mg/24h]	4346

5. Secondary Outcome

Title	Proteinuria at 6 Months
Description	Measured using 24 hour urine collection reported in mg/24 h
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Daratumumab
Arm/Group 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 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
Measure Participants	10
Median (Inter-Quartile Range) [mg/24h]	702

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Daratumumab
	Comments	Proteinuria baseline values compared to 6 month follow up values
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	t-test, 2 sided
	Comments

6. Secondary Outcome

Title	Proteinuria at 12 Months
Description	Measured using 24 hour urine collection reported in mg/24h
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Daratumumab
Arm/Group 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 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
Measure Participants	10
Median (Inter-Quartile Range) [mg/24h]	1264

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Daratumumab
	Comments	Proteinuria baseline values compared to 12 month follow up values
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	t-test, 2 sided
	Comments

7. Secondary Outcome

Title	Serum Creatinine at Baseline
Description	Blood serum collected and reported in mg/dL
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Daratumumab
Arm/Group 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 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
Measure Participants	10
Mean (Standard Deviation) [mg/dL]	1.36 (0.57)

8. Secondary Outcome

Title	Serum Creatinine at 6 Months
Description	Blood serum collected and reported in mg/dL
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Daratumumab
Arm/Group 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 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
Measure Participants	10
Mean (Standard Deviation) [mg/dL]	1.25 (0.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Daratumumab
	Comments	Serum creatinine baseline values compared to 6 month follow up values
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	t-test, 2 sided
	Comments

9. Secondary Outcome

Title	Serum Creatinine at 12 Months
Description	Blood serum collected and reported in mg/dL
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Daratumumab
Arm/Group 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 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
Measure Participants	10
Mean (Standard Deviation) [mg/dL]	1.25 (0.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Daratumumab
	Comments	Serum creatinine baseline values comparted to 12 month follow up values
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.16
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Adverse events were collected from baseline to end of study for a total of approximately 1 year on all participants.
Arm/Group Title	Daratumumab
Arm/Group 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 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
All Cause Mortality
	Daratumumab
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Serious Adverse Events
	Daratumumab
	Affected / at Risk (%)	# Events
Total	3/12 (25%)
Eye disorders
Eye Chemosis	1/12 (8.3%)	1
Acute Glaucoma	1/12 (8.3%)	1
General disorders
Fever	1/12 (8.3%)	1
Infections and infestations
C. difficile infection	1/12 (8.3%)	1
Nervous system disorders
Headache	1/12 (8.3%)	1
Other (Not Including Serious) Adverse Events
	Daratumumab
	Affected / at Risk (%)	# Events
Total	12/12 (100%)
Cardiac disorders
Vagal response	1/12 (8.3%)	1
Ear and labyrinth disorders
Tinnitus	1/12 (8.3%)	1
Eye disorders
Blurred Vision	4/12 (33.3%)	4
Watery eyes	2/12 (16.7%)	2
Gastrointestinal disorders
Constipation	1/12 (8.3%)	2
Rectal bleeding	1/12 (8.3%)	1
Bloating	1/12 (8.3%)	1
General disorders
Throat Irritation	6/12 (50%)	11
Tingling in feet	3/12 (25%)	4
Flushed	2/12 (16.7%)	3
Itching	2/12 (16.7%)	3
Sneezing	1/12 (8.3%)	1
Chest tightness	1/12 (8.3%)	1
Lip tingling	1/12 (8.3%)	2
Hoarse voice	1/12 (8.3%)	1
Sensation of facial swelling	1/12 (8.3%)	1
Fatigue	2/12 (16.7%)	3
Nausea	2/12 (16.7%)	2
Insomnia	1/12 (8.3%)	2
Night sweats	2/12 (16.7%)	3
Sore throat	2/12 (16.7%)	2
Chills	2/12 (16.7%)	2
Sore in mouth	1/12 (8.3%)	1
Foot pain	1/12 (8.3%)	1
Infections and infestations
URI	1/12 (8.3%)	1
Musculoskeletal and connective tissue disorders
Myalgia	3/12 (25%)	3
Leg cramps	2/12 (16.7%)	2
Low back pain	1/12 (8.3%)	1
Nervous system disorders
Headache	3/12 (25%)	3
Restless legs	1/12 (8.3%)	1
Renal and urinary disorders
UTI	2/12 (16.7%)	2
Urinary frequency	1/12 (8.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	7/12 (58.3%)	16
Congestion	7/12 (58.3%)	10
Skin and subcutaneous tissue disorders
Skin itchy at IV site	1/12 (8.3%)	2
Sore scalp	2/12 (16.7%)	2
Acne	1/12 (8.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.