Rituximab in Progressive Immunoglobulin A (IgA) Nephropathy

NCT00498368 | Completed Phase 4 Results DMC

• 1 other identifier: 07-001944
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 5

Brief Summary

This study was about IgA nephropathy, a form of kidney disease characterized by the presence of blood and protein in the urine. This study was done to determine if the medication rituximab could reduce protein in the patient's urine. Hypothesis: In patients with progressive IgA nephropathy an intravenous infusion of 1000 mg of rituximab on Day 1 and Day 15 and Days 168 and 182 is superior to conventional therapy in reducing 24 hour proteinuria, and slowing progression of chronic kidney disease.

Conditions

IgA Nephropathy

Keywords

Estimated glomerular filtration rate (GFR); Proteinuria; Renal Fibrosis

Outcome Measures

Primary Outcomes (1)

• Change in Proteinuria at 12 Months

  1 year

Secondary Outcomes (3)

• Biochemical Marker IgA at 12 Months

  12 months

• Biochemical Marker Gd-Immunoglobulin A Subclass 1 (IgA1) at 12 Months

  12 months

• Biochemical Marker Immunoglobulin G (IgG) AutoAb at 12 Months

  12 months

Study Arms (2)

Rituximab Plus ACE/ARB

EXPERIMENTAL

Intravenous Rituximab therapy, ACE/ARB combination therapy, and Omega-3 Fatty Acid Fish Oil Supplement

Drug: Intravenous Rituximab; Drug: ACE/ARB; Dietary Supplement: Omega-3 Fatty Acid Fish Oil Supplement

ACE/ARB

ACTIVE COMPARATOR

ACE/ARB therapy and Omega-3 Fatty Acid Fish Oil Supplement

Drug: ACE/ARB; Dietary Supplement: Omega-3 Fatty Acid Fish Oil Supplement

Interventions

Intravenous Rituximab DRUG

Rituximab Therapy \[27 Patients\] * Rituximab 1 gm IV on Treatment Day 1 * Rituximab 1 gm IV on Treatment Day 15 * Rituximab 1 gm IV on Treatment Day 168 * Rituximab 1 gm IV on Treatment Day 182

Also known as: Rituxan

Rituximab Plus ACE/ARB

ACE/ARB DRUG

ACE inhibitors and /or ARBs will be used to achieve a blood pressure goal of \<130/80 millimeters of mercury (mmHg). Patients not attaining the target blood pressure with an ACE inhibitor or ARB alone should be treated with the combination of ACE inhibitor (ACEi) + ARB

Also known as: Angiotensin II blockade

ACE/ARB; Rituximab Plus ACE/ARB

Omega-3 Fatty Acid Fish Oil Supplement DIETARY_SUPPLEMENT

Omega-3 Fatty Acid Fish Oil Supplement 3.6 gm eicosapentaenoic acid (EPA)/day

ACE/ARB; Rituximab Plus ACE/ARB

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any patient between the age of 18 and 70 years of age and able to give informed consent
• GFR by Cockcroft-Gault or MDRD equations \<90 mls/min and \>30 mls/min
• Greater than or equal to 1000 mg of proteinuria/24 hours while on stable ACEi, ARB or renin inhibitor therapy for 2 months. Patients receiving combination ACE or ARB or ACEi and a renin inhibitor for 2 months will only require 500mg/24 hours
• Blood pressure \<130/80 mmHg. The presence of hypertension is not required for study entry, but any patient requiring long term hypertensive medications must have blood pressure controlled \<130-80 mmHg, to be considered eligible for the study
• Female patients with IgA will be considered eligible for study entry if they have a negative urine or serum pregnancy test at the time of screening are agreeable to 2 years of contraception
• Biopsy proven IgA nephropathy and clinical features consistent with Henoch Schonlein Purpura will be considered eligible for the study
• Able to swallow the oral medications

You may not qualify if:

• Clinical and histologic evidence of IgA predominant Lupus nephritis
• Clinical and histologic evidence of idiopathic IgA forms of membranoproliferative glomerulonephritis
• Clinical evidence of cirrhosis, chronic active liver disease or known infection with hepatitis B, C or HIV
• Estimated GFR \<30 ml/min/1.73m² at the time of screening
• Greater than 50% glomerular senescence or cortical scarring on renal biopsy
• Active systemic infection or history of serious infection within one month of entry
• History of Crohn's disease or Celiac Sprue
• Positive pregnancy test or breast feeding at time of study entry or unwilling to comply with contraceptive measures
• Current or recent (within 30 days) exposure to any investigational drug
• Serum Cr \>3.5 mg/dl or Modification of Diet in Renal Disease (MDRD) calculated GFR \<30 mls/min
• Patients receiving \>6 months therapy with oral prednisone or glucocorticoid equivalent
• Live vaccine within 28 days of study enrollment.
• Patients with anaphylaxis and/or known allergic reactions to Rituximab
• Hemoglobin: \<8.5 gm/dL
• Platelets: \<100,000/mm

Sponsors & Collaborators

• Mayo Clinic: lead
• Ohio State University: collaborator
• Stanford University: collaborator
• University of North Carolina, Chapel Hill: collaborator
• Columbia University: collaborator
• Genentech, Inc.: collaborator
• Biogen: collaborator

Study Sites (5)

Stanford University

San Francisco, California, 94304, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of North Carolina, Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

The University of Ohio

Columbus, Ohio, 43210-1063, United States

Location

Related Publications (2)

• Lafayette RA, Canetta PA, Rovin BH, Appel GB, Novak J, Nath KA, Sethi S, Tumlin JA, Mehta K, Hogan M, Erickson S, Julian BA, Leung N, Enders FT, Brown R, Knoppova B, Hall S, Fervenza FC. A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction. J Am Soc Nephrol. 2017 Apr;28(4):1306-1313. doi: 10.1681/ASN.2016060640. Epub 2016 Nov 7.

  PMID: 27821627 RESULT

• Yeo SC, Liew A, Barratt J. Emerging therapies in immunoglobulin A nephropathy. Nephrology (Carlton). 2015 Nov;20(11):788-800. doi: 10.1111/nep.12527.

  PMID: 26032537 DERIVED

MeSH Terms

Conditions

Glomerulonephritis, IGA; Proteinuria

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Fernando Fervenza
• Organization: Mayo Clinic

Fervenza.Fernando@mayo.edu

507-255-3712

Study Officials

• Fernando C. Fervenza, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., Ph.D

Study Record Dates

• First Submitted: July 9, 2007
• First Posted: July 10, 2007
• Study Start: February 1, 2009
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: February 1, 2017
• Results First Posted: November 18, 2016

Record last verified: 2016-12

Locations

US (5)