Pilot Study of Rituximab to Treat Fibrillary Glomerulonephritis

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT02197767
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 11
• Location: 1
• Arm: 1
• Duration (Months): 29
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This pilot study is being done to see if the study medication, Rituximab, preserves kidney function after 12 months of taking the drug.

Condition or Disease	Intervention/Treatment	Phase
Fibrillary Glomerulonephritis	Drug: rituximab	Phase 2

Detailed Description

This is a Phase II, open-label pilot study to determine if the use of Rituximab reduces proteinuria over a 12 month period and is there preservation of kidney function with the use of this study drug. Each patient will be treated with 2 intravenous infusions of rituximab 1000 mg, two weeks apart for a total of 2 doses. Each patient will be retreated with identical 2 intravenous infusions of rituximab, two weeks apart at 6 months after the first infusion, irrespective of cluster of differentiation (CD) 20+ cell counts. Thus, each participant will receive 4 infusions of rituximab.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single Center Pilot Trial of Rituximab in the Treatment of Fibrillary Glomerulonephritis
• Study Start Date: Nov 1, 2014
• Actual Primary Completion Date: Apr 1, 2017
• Actual Study Completion Date: Apr 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: rituximab rituximab 1000 mg infusion two weeks apart for a total of two infusions. Retreated with identical rituximab 1000 mg infusion two weeks apart at six months after the first infusion for a grand total of four infusions.	Drug: rituximab; 1000 mg infusion; Other Names: Rituxan

Outcome Measures

Primary Outcome Measures

1. Change in 24 Hour Creatinine Clearance [Day 0, Day 365]

   Change in 24 hour creatinine clearance with the use of rituximab at 12 months. Creatinine clearance results are reported as milliliters/minute/patient's body surface area (mL/min/SA).

Secondary Outcome Measures

1. Change in Proteinuria [Day 0, Day 365]

   Change in proteinuria in milligrams (mg) with the use of rituximab at 12 months.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Fibrillary Glomerulonephritis with diagnostic biopsy performed within the last 2 years

• Proteinuria >1 gram

• Age > 18 years but < 80 years

• Adequately controlled blood pressure (BP<140/90 mmHg in >75% of the readings) for at least 3 months prior to enrollment with the use of (angiotensin converting enzyme inhibitors (ACEi) and/or angiotensin-receptor blockers (ARB), if tolerated.

• Women must be post- menopausal, surgically sterile or practicing a medically approved method of contraception

• Able and willing to give written informed consent and comply with the requirements of the study protocol

• Adequate renal function as indicated by estimated glomerular filtration rate (GFR) > 25 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD/EPI) formula or a quantified creatinine clearance >25 mL/min, and/or serum creatinine <3.0 mg/dL in the presence of ACEi/ARB therapy

• Adequate bone marrow function, as indicated by hemoglobin >7.0 gm/dL, white count >3.0 x 10(9), platelet count >100 x 10(9)

• Negative chest x-ray within one year

• Negative serum pregnancy test (for women of child bearing age)

• Normal organ function.

• Subject agrees to use an acceptable method of birth control during treatment and for twelve months after completion of treatment

• Subject has provided written informed consent

• Subject agrees to discontinue routine use of non-steroidal anti-inflammatory drugs

• Absolute Neutrophil Count (ANC): > 1000/ mm3

• Adequate liver function, as indicated by aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and total bilirubin < 2x upper limit or normal unless related to primary disease

• Negative HBsAg and anti-hepatitis B (HBc) lab values within 1 year of signing consent

Exclusion Criteria:

• Pregnancy (determined by a serum pregnancy test for all women of childbearing potential within 7 days of treatment), or lactating.

• Inability to comply with study and/or follow-up procedures

• History of HIV (a documented positive lab value within one year of enrollment)

• Presence of active infection

• New York Heart Association Classification III or IV heart disease

• Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix

• History of psychiatric disorder

• At the Investigator's discretion, receipt of a live vaccine within 4 weeks prior to randomization

• At the Investigator's discretion, positive Hepatitis C serology

• Known history of diabetes mellitus or a Hemoglobin A1c result > 6.0% within 90 days prior to enrollment

Contacts and Locations

Locations

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

Sponsors and Collaborators

• Mayo Clinic
• Genentech, Inc.

Investigators

• Principal Investigator: Stephen B. Erickson, M.D., Mayo Clinic

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 7, 2016

More Information

Publications

None provided.

• Responsible Party: Stephen B. Erickson, M.D., PI, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT02197767
• Other Study ID Numbers: 13-006694
• First Posted: Jul 23, 2014
• Last Update Posted: Feb 6, 2019
• Last Verified: Jan 1, 2019

• Keywords provided by Stephen B. Erickson, M.D., PI, Mayo Clinic: fibrillary glomerulonephritis; rituximab; Rituxan; MabThera; Zytux™
• Additional relevant MeSH terms: Glomerulonephritis; Rituximab

Study Results

Participant Flow

Arm/Group Title	Rituximab
Arm/Group Description	rituximab 1000 mg infusion two weeks apart for a total of two infusions. Retreated with identical rituximab 1000 mg infusion two weeks apart at six months after the first infusion for a grand total of four infusions. rituximab: 1000 mg infusion
Period Title: Overall Study
STARTED	11
COMPLETED	11
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Rituximab
Arm/Group Description	rituximab 1000 mg infusion two weeks apart for a total of two infusions. Retreated with identical rituximab 1000 mg infusion two weeks apart at six months after the first infusion for a grand total of four infusions. rituximab: 1000 mg infusion
Overall Participants	11
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.5 (2.03)
Sex: Female, Male (Count of Participants)
Female	8 72.7%
Male	3 27.3%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United States	11 100%

Outcome Measures

1. Primary Outcome

Title	Change in 24 Hour Creatinine Clearance
Description	Change in 24 hour creatinine clearance with the use of rituximab at 12 months. Creatinine clearance results are reported as milliliters/minute/patient's body surface area (mL/min/SA).
Time Frame	Day 0, Day 365

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab
Arm/Group Description	rituximab 1000 mg infusion two weeks apart for a total of two infusions. Retreated with identical rituximab 1000 mg infusion two weeks apart at six months after the first infusion for a grand total of four infusions. rituximab: 1000 mg infusion
Measure Participants	11
Mean (Standard Deviation) [mL/min/SA]	41.0 (15.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.072
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Change in Proteinuria
Description	Change in proteinuria in milligrams (mg) with the use of rituximab at 12 months.
Time Frame	Day 0, Day 365

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rituximab
Arm/Group Description	rituximab 1000 mg infusion two weeks apart for a total of two infusions. Retreated with identical rituximab 1000 mg infusion two weeks apart at six months after the first infusion for a grand total of four infusions. rituximab: 1000 mg infusion
Measure Participants	11
Mean (Standard Deviation) [mg]	2589.8 (1741.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rituximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.068
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Adverse event data was collected for the duration of the study until 30 days following the last administration of study treatment or study discontinuation/termination, whichever was earlier.
Arm/Group Title	Rituximab
Arm/Group Description	rituximab 1000 mg infusion two weeks apart for a total of two infusions. Retreated with identical rituximab 1000 mg infusion two weeks apart at six months after the first infusion for a grand total of four infusions. rituximab: 1000 mg infusion
All Cause Mortality
	Rituximab
	Affected / at Risk (%)	# Events
Total	0/11 (0%)
Serious Adverse Events
	Rituximab
	Affected / at Risk (%)	# Events
Total	0/11 (0%)
Other (Not Including Serious) Adverse Events
	Rituximab
	Affected / at Risk (%)	# Events
Total	0/11 (0%)

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.