CellCept in p-ANCA Vasculitis

Microscopic Polyangiitis Clinical Trial

Official title:

A Pilot Study of Mycophenolate Mofetil (MMF) in Patients With p-ANCA Microscopic Polyangiitis and Mild to Moderate Renal Dysfunction.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00405860
• Other study ID #: 1679-02
• Status: Completed
• Phase: Phase 1
• First received: November 29, 2006
• Last updated: March 21, 2011
• Start date: December 2002
• Est. completion date: July 2008

Study information

• Verified date: March 2011
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Microscopic polyangiitis (MP) is a primary systemic vasculitis predominantly affecting small blood vessels. Following the widespread introduction of ANCA testing, the primary systemic vasculitis (SV), Wegener?s granulomatosis (WG) and microscopic polyangiitis (MP) appear to be more frequent than was previously thought (see definitions in Appendix 6). In addition, the existence of early and organ-limited forms of these diseases, such as renal-limited vasculitis (RLV) is now clearly recognized. Their annual incidence exceeds 20 per million per year and they account for at least 5 % of the causes of end stage renal failure. The two diseases share many features of their histology, serology and response to treatment, pointing to similarities in their pathogenesis, which have justified a common approach to their management. The standard treatment with corticosteroids (CS) and cyclophosphamide (CYC) is usually effective at controlling active disease but continued treatment is necessary to prevent disease relapse. Due to the cumulative toxicity associated with CYC treatment, alternatives have been looked for. Mycophenolate mofetil (MMF) has been used to treat patients with a variety of immune-mediated nephritides, including ANCA-associated vasculitis, with less toxicity than CYC but with variable outcome. The present trial will examine whether substitution of oral CYC with oral MMF is equally efficient for induction of remission with less adverse effects in cases of MP with mild to moderate renal involvement. All patients will receive the same regimen of oral prednisone + MMF. Prednisone will be tapered to a stop after 24 weeks but MMF will continue for a total of 18 months unless there is worsening or persistent disease. The trial ends after 18 months.

Description:

1. Patients will receive I.V. methylprednisone, or I.V. dexamethazone, oral prednisone and oral MMF therapy as outlined in table 2.

2. MMF will be initiated within the first 1-2 weeks of the start of steroids. Patients will receive CellCept, 750 mg po b.i.d for the first week. Dose will be increased to 1000 mg po b.i.d for the second week, and thereafter, according to blood levels and patient tolerance. Target blood levels are 1 ? 3.5 g/ml. Treatment will be for a total of 18 months. This is based on the published dose-dependent adverse effect profiles in transplant patients (31-32) and on reports that lower doses are ineffective and shorter courses (less then 6 months) result in relapses or failure of therapy (25). Dose will be reduced in patient who can not tolerate MMF at the above dose.

2) Relapse treatment to follow guidelines for relapse regimens. 3) After 18 months, all medications will be tapered to a full stop unless disease is active or grumbling.

4) Pneumocystis pneumonia prophylaxis will be used during the trial (with sulfamethoxazole/trimethoprim, or Dapsone or Mepron if allergic to sulfa).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

1. Active microscopic polyangiitis

2. Active urinary sediment (>25 rbc/hpf, red cell casts or dysmorphic red cells)

3. Renal biopsy compatible with the diagnosis of microscopic polyangiitis, or diagnosis demonstrated by the presence of hematuria, proteinuria, and dysmorphic red blood cells, and / or red blood casts when biopsy is contraindicated.

4. Positive p-ANCA (MPO ELISA)

5. Serum creatinine < 3.0mg/dl.

6. Age 18 years or over.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Microscopic Polyangiitis
• MPO-ANCA Vasculitis
• Systemic Vasculitis
• Vasculitis

Intervention

Drug:
• CellCept (mycophenolate mofetil)

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	Roche Pharma AG

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary endpoint is successful induction of remission as defined in Appendix 6 within 6 months.
Secondary	Major relapse necessitating a switch to induction OCS/CYC treatment or more aggressive treatment (e.g. plasma exchange).
Secondary	Minor relapses that can effectively be controlled by a transient, non-toxic increase in OCS
Secondary	Intolerance to trial medications and adverse effects. Adverse effects will be monitored