Clinical Trial of Mycophenolate Versus Cyclophosphamide in ANCA Vasculitis (MYCYC)

This study has been completed.
Sponsor:
Collaborators:
Aspreva Pharmaceuticals
Vifor Pharma
Information provided by (Responsible Party):
David Jayne, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT00414128
First received: December 19, 2006
Last updated: December 5, 2013
Last verified: December 2013
  Purpose

The purpose of this study is to investigate whether mycophenolate mofetil is effective as treatment for new cases of ANCA associated vasculitis.


Condition Intervention Phase
Vasculitis
Drug: mycophenolate mofetil
Drug: cyclophosphamide
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomised Clinical Trial of Mycophenolate Mofetil Versus Cyclophosphamide for Remission Induction in ANCA Associated Vasculitis.

Resource links provided by NLM:


Further study details as provided by Cambridge University Hospitals NHS Foundation Trust:

Primary Outcome Measures:
  • Remission rates at 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Assessed by BVAS score of zero on 2 consecutive assessments


Enrollment: 140
Study Start Date: March 2007
Study Completion Date: February 2013
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: mycophenolate mofetil
Mycophenolate mofetil for 3-6 months until in stable remission, dose 2-3g/day
Drug: mycophenolate mofetil
2-3g/day for 3-6 months, in tablet, capsule or liquid form
Other Name: Cellcept
Active Comparator: cyclophosphamide
pulsed intravenous cyclophosphamide 15mg/kg for 3-6 months (6-10 doses)until in stable remission
Drug: cyclophosphamide
intravenous cyclophosphamide, 15mg/kg with dose reductions according to age and renal function, for 3-6 months (6-10 doses total)
Other Name: cytoxan

Detailed Description:

There is a clear need for improved therapy in ANCA associated vasculitis where current treatments are toxic and contribute to poor outcomes. Conventional therapy combines cyclophosphamide with prednisolone but is associated with severe adverse events in 35%, early mortality, malignancy and infertility. Mycophenolate mofetil (MMF) is a newer immunosuppressive drug which has superior efficacy to azathioprine in solid organ transplantation. MMF is an effective alternative to cyclophosphamide in lupus nephritis. Open label studies and retrospective surveys point to the efficacy and low toxicity of MMF in vasculitis.

We hypothesise that MMF not be less effective than cyclophosphamide for remission induction in AASV. 140 new patients will be randomised to MMF 3g/day or a European consensus intravenous cyclophosphamide regimen, with the same prednisolone dosing. Following a six month induction course all patients will receive consensus remission maintenance treatment with azathioprine and prednisolone. The primary end-point will be remission rate by six months, secondary end-points include relapse rate at 18 months and safety. The trial will be conducted in 10 countries by members of the European Vasculitis Study Group (EUVAS). The trial duration will be 42 months (24 months recruitment, 18 months follow up).

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Inclusion (requires all):

  • New diagnosis of AASV (WG or MPA) (within the previous six months)
  • Active disease (defined by at least one major or three minor BVAS 2003 items, see appendix 1)
  • ANCA positivity (c-ANCA and PR3-ANCA or p-ANCA and MPO-ANCA) or histology confirming active vasculitis from any organ (see appendix )
  • Written informed consent

Exclusion Criteria:

  • Previous treatment with:

    • MMF: more than two weeks ever.
    • Cyclophosphamide: more than two weeks daily oral or more than 1 pulse of IV CYC (15mg/kg)
    • Rituximab or high dose intravenous immunoglobulin within the last twelve months
  • Active infection (including hepatitis B, C, HIV and tuberculosis).
  • Known hypersensitivity to MMF, AZA or CYC.
  • Cancer or an individual history of cancer (other than resected basal cell skin carcinoma).
  • Females who are pregnant, breast feeding, or at risk of pregnancy and not using a medically acceptable form of contraception.
  • Any condition judged by the investigator that would cause the study to be detrimental to the patient.
  • Any other multi-system autoimmune disease including Churg Strauss angiitis, SLE, anti GBM disease and cryoglobulinaemia.
  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: NCT00414128

Locations
United Kingdom
Addenbrookes Hospital
Cambridge, Cambridgeshire, United Kingdom, CB22QQ
Sponsors and Collaborators
Cambridge University Hospitals NHS Foundation Trust
Aspreva Pharmaceuticals
Vifor Pharma
Investigators
Principal Investigator: David Jayne Addenbrooke's Hospital, Cambridge, UK
Principal Investigator: Lorraine Harper Birmingham University, UK
Principal Investigator: Rachel Jones Addenbrooke's Hospital, UK
  More Information

Additional Information:
No publications provided

Responsible Party: David Jayne, Drs David Jayne Consultant in Nephrology and Vasculitis, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT00414128     History of Changes
Other Study ID Numbers: MYCYC, Eudract: 2006-001663-33
Study First Received: December 19, 2006
Last Updated: December 5, 2013
Health Authority: European Union: European Medicines Agency

Keywords provided by Cambridge University Hospitals NHS Foundation Trust:
vasculitis
ANCA
mycophenolate mofetil
cyclophosphamide
Anti neutrophil cytoplasm antibody associated vasculitis

Additional relevant MeSH terms:
Vasculitis
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Vascular Diseases
Cardiovascular Diseases
Systemic Vasculitis
Autoimmune Diseases
Immune System Diseases
Cyclophosphamide
Mycophenolate mofetil
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014