Trial record 7 of 222 for:    "Glomerulonephritis"

Pilot Study of Rituximab for Membranoproliferative Glomerulonephritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
John Dillon, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00275613
First received: January 10, 2006
Last updated: January 15, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Glomerulonephritis, Membranoproliferative
Drug: Rituximab
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of Rituximab for Membranoproliferative Glomerulonephritis

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Proteinuria [ Time Frame: 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. ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Serum albumin [ Time Frame: 3, 6, 9 and 12 months ] [ Designated as safety issue: No ]
    Change in serum albumin concentration

  • Serum cholesterol [ Time Frame: 6 and 9 month timepoints ] [ Designated as safety issue: No ]
    Change in serum cholesterol levels


Enrollment: 10
Study Start Date: November 2005
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituximab, IV infusion
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
The Rituximab dose is 1000 mg (1 gm) given as an IV infusion every two weeks for 2 doses (days 1 and 15)
Other Name: Rituxan

Detailed Description:

Membranoproliferative glomerulonephritis (MPGN) is a relatively-rare, immune-mediated glomerular disease. There is no accepted therapy and all current therapies are inadequate. Current therapeutic options include immunosuppression with corticosteroids alone or in combination with alkylating agents, antiplatelet therapy with aspirin and/or dipyridamole and/or warfarin, and angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers. As with other glomerular diseases the amount of protein in the urine correlates well with the long-term prognosis. Thus, this parameter has been used in previous studies, and will be used in this study, as the primary indicator of therapeutic efficacy. We propose a pilot study to test the hypothesis that selective B lymphocyte depletion will result in disappearance of pathogenic antibodies and induce remission of proteinuria in patients with idiopathic membranoproliferative glomerulonephritis. Our population will be 10 adults with MPGN involving either the native kidneys or a renal transplant. We will enroll patients with a glomerular filtration rate (GFR) greater than or equal to 25 ml/min, as estimated by creatinine clearance, and with a 24 hour urinary ratio of protein to creatinine greater than or equal to 1, while receiving an angiotensin converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB). Patients will receive Rituximab 1g on Day 1 and 15. Patients will be followed for 1 year following completion of treatment. The primary outcome will be the change in urinary protein excretion at 6 months. Secondary outcomes will include changes in the GFR, changes in urinary protein excretion at 3, 9, and 12 months, the rate of change in urinary protein excretion, serum albumin concentration, serum cholesterol, the number of complete and partial remissions, time to remission, and the number of relapses.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Lack of peripheral venous access
  • Drug,alcohol or chemical abuse within 6 months prior to screening
  • Pregnancy(negative serum pregnancy test performed all women of childbearing potential within 7 days of treatment)
  • Lactation
  • Concomitant malignancies/previous malignancies within last 5 years, with the exception of adequately treated basal/squamous cell carcinoma of skin or carcinoma of cervix
  • Major psychiatric disorder
  • Significant cardiac or pulmonary disease
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory suspicion of a disease/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 complications
  • Inability to comply with study and follow-up procedures

Laboratory Exclusion Criteria (Screening):

  • Hemoglobin:< 8.5 gm/dL
  • Platelets:< 100,000/mm
  • Total bilirubin,AST/alkaline phosphatase > 2.5 x Upper Limit of Normal unless related to primary disease
  • Positive Hepatitis B or C serology
  • Positive HIV
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00275613

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: John J. Dillon, M.D., M.S. Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: John Dillon, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00275613     History of Changes
Other Study ID Numbers: 976-05
Study First Received: January 10, 2006
Last Updated: January 15, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Glomerulonephritis
Glomerulonephritis, Membranoproliferative
Nephritis
Kidney Diseases
Urologic Diseases
Immune System Diseases
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 22, 2014