Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

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

This study has been completed.
Information provided by:
Nippon Kayaku Co.,Ltd. Identifier:
First received: September 14, 2007
Last updated: January 16, 2017
Last verified: September 2007
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 Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status.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 of Vasculitis [ Time Frame: At Entry (Day 1 of Cycle 1), Day 22 of cycles 1-6, up to 24 weeks ]

    The primary efficacy outcome measure was remission of vasculitis. Complete remission was defined as a Birmingham vasculitis activity score (BVAS) of 0 sustained for at least 2 months. Partial remission was defined as a reduction in BVAS of 50% or more, sustained for at least 2 months, when compared with the BVAS at entry.

    Entry required active Wegener's granulomatosis with a BVAS >= 4. Their disease had to be active, as measured with BVAS in which clinical manifestations caused by active vasculitis are scored on a list of predefined organ-specific items.

Secondary Outcome Measures:
  • Duration of Clinical Response [ Time Frame: At Entry (Day 1 of Cycle 1), Day 22 of cycles 1-6, up to 24 weeks, End of treatment period, and 3 and 6 months of follow-up period ]
    Time from Complete Remission or Partial Remission to Relapse.

  • Haematuria [ Time Frame: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks ]
    Assessment of anti-inflammatory activity of gusperimus using surrogate marker: number of hematuria-positive patients.

  • Creatinine [ Time Frame: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks ]
    Assessment of anti-inflammatory activity of gusperimus using surrogate marker: serum creatinine level

  • ANCA [ Time Frame: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks ]

    Assessment of anti-neutrophil cytoplasmic antibody (ANCA): Number of ANCA-positive patients was counted.

    ANCA are highly associatred with active WG, with c-ANCA titres observed in 90% of WG. In addition to their diagnostic value, it has been suggested that ANCA may have a predictive value for relapse in patients with systemic vasculitis.

  • CRP [ Time Frame: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks ]
    Assessment of anti-inflammatory activity of gusperimus using surrogate marker: serum C-reactive protein level.

  • Vasculitis Damage Index (VDI) [ Time Frame: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks, 6 months of follow-up period ]
    Assessment of the degree of irreversible damage due to the vasculitis using VDI scoring system. The VDI comprises 64 items of damage (grouped into 11 organ-based systems). Total VDI score is 0 - 64. The higher scores represent the more severe damage occurred in patients. The VDI score can either increase or remain the same over time.

  • SF-36 [ Time Frame: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks ]
    Assessment of the impact of gusperimus on general health using the Short form-36 (SF-36) questionaire. The SF-36 is a self-report, 36 item survey measuring health-related quality-of-life. Thirty-five items are used to construct 8 scales: (1) physical functioning, (2) role physical, (3) bodily pain, (4) general health, (5) vitality, (6) social function, (7) role emotional, and (8) mental health. Raw scores are calculated as the sum of re-coded scale items and transformed to a 0 to 100 scale. If scores for all 8 scales are available, two summary measures known as component scores are derived: the Physical Health Component Score (PCS) and the Mental Health Component Score (MCS). First each scale standardized to the relevant population. Then PCS and MCS are calculated as the weighted sum of standardized scores. All scales and the component scores are positively scored so that higher scores represent better health-related quality-of-life.

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
Drug: Gusperimus
SC, 0.5mg/kg/day, consecutive 21 days administration, 1 to 2 weeks rest, 6 cycles


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
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 identifier: NCT00530075

Czech Republic
General Faculty Hospital
Prague, Czech Republic, 12808
Reumatologisk Klinik
Copenhagen, Denmark, 2100
Universitatsklinikum Schleswig-Holstein
Luebeck, Germany, 23538
University Hospital Maastricht
Maastricht, Netherlands, 6202
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.
Principal Investigator: David Jayne Addenbrookes Hospital
  More Information

Additional Information:
Responsible Party: Peter A. Heinzel, Ph.D., Clinical and Scientific Department, Euro Nippon Kayaku GmbH Identifier: NCT00530075     History of Changes
Other Study ID Numbers: 102
Study First Received: September 14, 2007
Results First Received: April 18, 2016
Last Updated: January 16, 2017

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

Additional relevant MeSH terms:
Granulomatosis with Polyangiitis
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Systemic Vasculitis
Vascular Diseases
Cardiovascular Diseases
Autoimmune Diseases
Immune System Diseases
Antibiotics, Antineoplastic
Antineoplastic Agents
Hypoglycemic Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Radiation-Protective Agents
Protective Agents processed this record on May 23, 2017