Effect of Rituximab in Treatment of Membranoproliferative Glomerulonephritis
Primary Purpose
Membranoproliferative Glomerulonephritis
Status
Unknown status
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Rituximab
Cyclosporin
Sponsored by
About this trial
This is an interventional treatment trial for Membranoproliferative Glomerulonephritis
Eligibility 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 angiotensin converting enzyme inhibitor/angiotensin receptor blocker 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.
- 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.
- Estimated glomerular filtration rate ≥ 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.
- Negative serum pregnancy test (for women of child bearing age).
Exclusion Criteria:
- Age <18 years.
- Secondary MPGN.
- Presence or suspicion of active infection.
- Pregnancy.
- Concomitant malignancies, Major psychiatric disorder. Significant cardiac or pulmonary disease and 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.
Laboratory Exclusion Criteria (Screening):
- Hemoglobin:< 8.5 gm/dL
- Platelets:< 100,000/mm
- Total bilirubin, Aspartate amino transferase, alkaline phosphatase > 2.5 x Upper Limit of Normal unless related to primary disease
- Positive Hepatitis B or C serology
- Positive human immunodeficiency virus
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
study group
control group
Arm Description
Rituximab is given in 2 doses (1 gm each dose) to a group of15 patients with primary membranoproliferative glomerulonephritis at (0 - after 2 weeks)
Cyclosporine is given orally in a dose of 2mg/kg/d for 3 months to another group of patients with primary membranoproliferative glomerulonephritis.
Outcomes
Primary Outcome Measures
effect of Rituximab on proteinuria
measured through urinary protein/ creatinine ratio
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03180723
Brief Title
Effect of Rituximab in Treatment of Membranoproliferative Glomerulonephritis
Official Title
Effect of Rituximab in Treatment of Primary Membranoproliferative Glomerulonephritis
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Unknown status
Study Start Date
July 1, 2017 (Anticipated)
Primary Completion Date
July 2019 (Anticipated)
Study Completion Date
December 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Assiut University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
Type I membranoproliferative glomerulonephritis (MPGN) is a relatively uncommon glomerular disease, constituting 1.8% of renal biopsies performed in Rochester, minnesota, United States of America, at the Mayo Clinic, between 1993 and 2008. The prognosis of idiopathic Type I MPGN is relatively poor. Recently, Irish series, slightly more than 50% of patients developed end stage renal disease after a mean follow up of 14 years . The disease may recur after renal transplantation . High-dose glucocorticoids have been used to treat this disease in children but there is no established treatment in adults.
Detailed Description
Type I MPGN is associated with a variety of disorders, including hepatitis, especially hepatitis C, cryoglobulinemia, monoclonal gammopathies, systemic lupus erythematosus, and bacterial endocarditis or other chronic bacterial infections . Idiopathic Type I MPGN is rare. Biopsy samples usually stain for C3 and properdin. However, immunoglobulin G is also present in most cases, especially if the biopsy is performed early in the course of the disease suggesting antibody production as a possible therapeutic target.
Rituximab is a chimeric murine/human immunoglobulin g1 kappa monoclonal antibody targeting the cluster of differentiation 20 antigen found on pre-B and mature B lymphocytes, but not on hematopoietic stem cells, pro-B cells, normal plasma cells or the cells of other normal tissues. In the United States it was approved by the US Food and Drug Administration in 1997 for non-Hodgkin's lymphoma and was later approved for rheumatoid arthritis. Intravenous administration of rituximab results in rapid, selective, prolonged B cell depletion.
Anecdotal reports have demonstrated the efficacy of rituximab in treating MPGN secondary to chronic lymphocytic leukemia. Rituximab has also been shown to be effective in patients with MPGN related to a monoclonal gammopathy.
In an open label trial with rituximab, six patients with MPGN type I were treated with rituximab 1000 mg on days 1 and 15 and followed for 1 year. Proteinuria fell in all patients, at all time points, after rituximab administration. Renal function did not change.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Membranoproliferative Glomerulonephritis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
study group
Arm Type
Experimental
Arm Description
Rituximab is given in 2 doses (1 gm each dose) to a group of15 patients with primary membranoproliferative glomerulonephritis at (0 - after 2 weeks)
Arm Title
control group
Arm Type
Active Comparator
Arm Description
Cyclosporine is given orally in a dose of 2mg/kg/d for 3 months to another group of patients with primary membranoproliferative glomerulonephritis.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Intravenous injection
Intervention Type
Drug
Intervention Name(s)
Cyclosporin
Intervention Description
Oral tablets
Primary Outcome Measure Information:
Title
effect of Rituximab on proteinuria
Description
measured through urinary protein/ creatinine ratio
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 angiotensin converting enzyme inhibitor/angiotensin receptor blocker 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.
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.
Estimated glomerular filtration rate ≥ 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.
Negative serum pregnancy test (for women of child bearing age).
Exclusion Criteria:
Age <18 years.
Secondary MPGN.
Presence or suspicion of active infection.
Pregnancy.
Concomitant malignancies, Major psychiatric disorder. Significant cardiac or pulmonary disease and 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.
Laboratory Exclusion Criteria (Screening):
Hemoglobin:< 8.5 gm/dL
Platelets:< 100,000/mm
Total bilirubin, Aspartate amino transferase, alkaline phosphatase > 2.5 x Upper Limit of Normal unless related to primary disease
Positive Hepatitis B or C serology
Positive human immunodeficiency virus
12. IPD Sharing Statement
Citations:
PubMed Identifier
22445472
Citation
Dillon JJ, Hladunewich M, Haley WE, Reich HN, Cattran DC, Fervenza FC. Rituximab therapy for Type I membranoproliferative glomerulonephritis. Clin Nephrol. 2012 Apr;77(4):290-5. doi: 10.5414/cn107299.
Results Reference
background
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Effect of Rituximab in Treatment of Membranoproliferative Glomerulonephritis
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