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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

About this trial

This is an interventional treatment trial for Membranoproliferative Glomerulonephritis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

NCT ID

NCT03180723

First Posted

June 3, 2017

Last Updated

June 15, 2017

Sponsor

Assiut University

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

Studies a U.S. FDA-regulated Device Product

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

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.

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Effect of Rituximab in Treatment of Membranoproliferative Glomerulonephritis

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