Pilot Study of Rituximab for Membranoproliferative Glomerulonephritis

NCT00275613 | Completed Phase 1 DMC

• 1 other identifier: 976-05
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Membranoproliferative glomerulonephritis (MPGN) is a relatively-rare, immune-mediated kidney disease. All current therapies are inadequate and MPGN frequently leads to kidney failure. This study is a 10 patient trial of the monoclonal antibody rituximab for adult patients with MPGN. Study patients will receive 2 doses of rituximab intravenously on days 1 and 15 and will then be followed for 1 year.

Conditions

Glomerulonephritis, Membranoproliferative

Outcome Measures

Primary Outcomes (1)

• Proteinuria

  1. Complete remission (CR) UP ≤ 0.3 g, without doubling of serum creatinine 2. Partial remission (PR) Reduction in UP of \> 50% plus final UP ≤ 3.5 g but \>0.3 g, without doubling of serum creatinine 3. Limited response (LR) Reduction in UP of \> 50% with final UP \> 3.5 g, without doubling of serum creatinine 4. Non-response (NR) Reduction in UP of \< 50%. (includes progression of UP), without doubling of serum creatinine 5. Progression Proteinuria increases by \> 50% or serum creatinine doubles 6. Relapse New development of nephrotic range proteinuria, i.e. \> 3.5 g/day

  The primary endpoints are based on quantitative changes in urine protein measured at 6 months. Additional evaluations of urine protein will be done at 3, 9, and 12 months.

Secondary Outcomes (2)

• Serum albumin

  3, 6, 9 and 12 months

• Serum cholesterol

  6 and 9 month timepoints

Study Arms (1)

Rituximab, IV infusion

EXPERIMENTAL

The Rituximab dose is 1000 mg (1 gm) given as an IV infusion every two weeks for 2 doses (days 1 and 15)

Drug: Rituximab

Interventions

Rituximab DRUG

The Rituximab dose is 1000 mg (1 gm) given as an IV infusion every two weeks for 2 doses (days 1 and 15)

Also known as: Rituxan

Rituximab, IV infusion

Eligibility Criteria

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

You may qualify if:

• MPGN either native/renal transplant kidneys with biopsy last 3 years
• Age \> 18 years
• Urinary protein to creatinine ratio \> 1.0 in a 24-hour urine collection, despite ACE inhibitor/ARB treatment
• Patients need to be treated with an ACEI and/or ARB, for at least 3 months prior to enrollment with the systolic blood pressure \< 140 mm Hg for at least 75% of readings. Goal systolic blood pressure will be \< 130 mm Hg.)
• Women must be post-menopausal, surgically sterile or practicing a medically approved method of contraception
• Patients intolerant of ACE inhibitors/ARBs may enter the study without being treated with these agents
• Able/willing to give written informed consent/comply with the requirements of study protocol
• Estimated GFR ≥ 25 ml/min per 1.73m\^2 in the presence of ACE inhibitor/ARB therapy. The GFR will be estimated using the 4 variable Modification of Diet in Renal Disease (MDRD) equation/National Kidney Foundation - Chronic Kidney Disease (NKF-CKD) guidelines
• Adequate liver function, indicated by bilirubin, aspartate aminotransferase (AST), and alkaline phosphatase levels not more than 2.5 times the upper normal limit
• Negative serum pregnancy test (for women of child bearing age)
• Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment

You may not qualify if:

• Age \<18 years.
• Estimated GFR \< 25 ml/min per 1.73 m\^2
• Concurrent use of immunosuppressive therapy with the exceptions of prednisone 10 mg/day or less or an equivalent amount of another glucocorticoid or, among transplant patients, stable or decreasing transplant immunosuppression. Patient must be off immunosuppressive medications for \> 3 months prior to enrollment into the study
• Medical conditions causing MPGN (e.g. HIV, hepatitis B, hepatitis C, systemic lupus erythematosus, monoclonal gammopathies). Patients with idiopathic cryoglobulinemia will not be excluded
• Presence or suspicion of active infection
• Type 1 or type 2 diabetes mellitus
• Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer)
• Receipt of a live vaccine within 4 weeks prior to randomization
• Previous Treatment with Rituximab (MabThera®/Rituxan®) or another B-cell depleting antibody
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• Human immunodeficiency virus (HIV)
• Hepatitis B or C
• History of recurrent significant or recurrent bacterial infections
• Known active bacterial, viral fungal mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
• Ongoing use of high dose steroids(\> 10 mg/day)or unstable steroid dose past 4 weeks

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Glomerulonephritis, Membranoproliferative

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; Immune System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• John J. Dillon, M.D., M.S.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: January 10, 2006
• First Posted: January 12, 2006
• Study Start: November 1, 2005
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: January 16, 2013

Record last verified: 2013-01

Locations

US (1)