Phase II Study on Gusperimus in Patients With Refractory Wegener's Granulomatosis

This study has been completed.
Sponsor:
Information provided by:
Nippon Kayaku Co.,Ltd.
ClinicalTrials.gov Identifier:
NCT00530075
First received: September 14, 2007
Last updated: February 13, 2008
Last verified: September 2007
  Purpose

Wegener's granulomatosis is a primary systemic vasculitis characterized by granulomatous and necrotizing inflammation predominantly affecting the respiratory tract and the kidneys. Conventional therapy of Wegener's granulomatosis with cyclophosphamide and corticosteroids is limited by incomplete remissions and a high relapse rate. Patients accumulate irreversible damage due to the disease and the consequences of prolonged drug exposure. The efficacy and safety of an alternative immunosuppressive drug, gusperimus, was evaluated in patients with refractory disease. A prospective, international, nulti-centre, single limb, open label study. Entry required active Wegener's granulomatosis with a Birmingham Vasculitis Activity Score (BVAS) >=4 and previous therapy with cyclophosphamide or methotrexate. Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status. Gusperimus, 0.5mg/kg/day, was self-administered by subcutaneous injection in six treatment cycles of 21 days with a seven day washout between cycles. Cycles were stopped early for white blood count < 4,000/mm3. The primary endpoint was complete remission (BVAS=0 for at least 2 months) or partial remission (BVAS<50% of entry score). After the sixth cycle azathioprine was commenced and follow-up continued for a further six months.


Condition Intervention Phase
Wegener's Granulomatosis
Drug: Gusperimus
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study on Gusperimus in Patients With Refractory Wegener's Granulomatosis

Resource links provided by NLM:


Further study details as provided by Nippon Kayaku Co.,Ltd.:

Primary Outcome Measures:
  • Remission (defined by Birmingham Vasculitis Activity Score (BVAS)) [ Time Frame: Screening, Day1 of Cycle1, End of each cycle ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Duration of clinical response, Laboratory markers (CRP, ESR, urine-analysis, ANCA), Damage as measured by the Vasculitis Damage Index, Patient function as measured by the SF-36 score, Adverse events [ Time Frame: Screening, Day1 of Cycle1, End of each cycle; for Adverse events, throughaout study period ] [ Designated as safety issue: Yes ]

Enrollment: 45
Study Start Date: December 2003
Study Completion Date: February 2006
Primary Completion Date: February 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Gusperimus
Drug: Gusperimus
SC, 0.5mg/kg/day, consecutive 21 days administration, 1 to 2 weeks rest, 6 cycles

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented diagnosis of WG according to American College of Rheumatology (ACR) and Chapel Hill Consensus Conference (CHCC) definition
  • BVAS >= 4
  • Total disease duration >= 3 months treated with CYC or >= 6 months with MTX
  • Age 18 - 80
  • WBC >= 4,000/mm3, haemoglobin >= 8g/dl, neutrophils >= 2,500/mm3, platelets >= 100,000/mm3
  • ALT, bilirubin and alkaline phosphatase levels within 2x the upper limits of normal
  • Documented to be non-pregnant by serum/urine pregnancy test
  • Willing to participate in this study
  • Provide signed informed consent
  • Able and prepared to self-administer the study drug or have a close friend/relative able to do this

Exclusion Criteria:

  • Participation in another clinical research study
  • Pregnant or nursing mothers and women of childbearing age not using appropriate contraception
  • Clear evidence of active disease due to bacteria/viral infection
  • Patient has an unacceptable risk for participation in a study of immunosuppressive therapy
  • History of substance abuse or psychotic disorders
  • Previous treatment with Gusperimus
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00530075

Locations
Czech Republic
General Faculty Hospital
Prague, Czech Republic, 12808
Denmark
Reumatologisk Klinik
Copenhagen, Denmark, 2100
Germany
Universitatsklinikum Schleswig-Holstein
Luebeck, Germany, 23538
Netherlands
University Hospital Maastricht
Maastricht, Netherlands, 6202
Sweden
Karolinska University Hospital
Stockholm, Sweden, 14186
United Kingdom
Western General Hospital
Edinburgh, Scotland, United Kingdom, EH4 2XU
Addenbrookes Hospital
Cambridge, United Kingdom, CB2 2QQ
Sponsors and Collaborators
Nippon Kayaku Co.,Ltd.
Investigators
Principal Investigator: David Jayne Addenbrookes Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Peter A. Heinzel, Ph.D., Clinical and Scientific Department, Euro Nippon Kayaku GmbH
ClinicalTrials.gov Identifier: NCT00530075     History of Changes
Other Study ID Numbers: 102
Study First Received: September 14, 2007
Last Updated: February 13, 2008
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: Medicines Evaluation Board
Sweden: Medical Products Agency

Keywords provided by Nippon Kayaku Co.,Ltd.:
Wegener Granulomatosis
Vasculitis
Gusperimus
Immunosuppression

Additional relevant MeSH terms:
Wegener Granulomatosis
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Systemic Vasculitis
Vasculitis
Vascular Diseases
Cardiovascular Diseases
Gusperimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Radiation-Protective Agents
Protective Agents

ClinicalTrials.gov processed this record on April 17, 2014