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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: January 16, 2017
Last verified: September 2007
September 14, 2007
January 16, 2017
December 2003
February 2006   (Final data collection date for primary outcome measure)
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.

Remission (defined by Barmingham Vasculitis Activity Score (BVAS)) [ Time Frame: Screening, Day1 of Cycle1, End of each cycle ]
Complete list of historical versions of study NCT00530075 on ClinicalTrials.gov Archive Site
  • 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.
Duration of clinical response, Laboratory markers (CRP, ESR, urine-analysis, ANCA), Damage as measured by the Vasculitis Damage Index, Patient function as measyred by the SF-36 score, Adverse events [ Time Frame: Screening, Day1 of Cycle1, End of each cycle; for Adverse events, throughaout study period ]
Not Provided
Not Provided
 
Phase II Study on Gusperimus in Patients With Refractory Wegener's Granulomatosis
Phase II Study on Gusperimus in Patients With Refractory Wegener's Granulomatosis
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.
Not Provided
Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Wegener's Granulomatosis
Drug: Gusperimus
SC, 0.5mg/kg/day, consecutive 21 days administration, 1 to 2 weeks rest, 6 cycles
Experimental: 1
Gusperimus
Intervention: Drug: Gusperimus
Birck R, Warnatz K, Lorenz HM, Choi M, Haubitz M, Grünke M, Peter HH, Kalden JR, Göbel U, Drexler JM, Hotta O, Nowack R, Van Der Woude FJ. 15-Deoxyspergualin in patients with refractory ANCA-associated systemic vasculitis: a six-month open-label trial to evaluate safety and efficacy. J Am Soc Nephrol. 2003 Feb;14(2):440-7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
45
February 2006
February 2006   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 80 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Czech Republic,   Denmark,   Germany,   Netherlands,   Sweden,   United Kingdom
 
 
NCT00530075
102
No
Not Provided
Not Provided
Peter A. Heinzel, Ph.D., Clinical and Scientific Department, Euro Nippon Kayaku GmbH
Nippon Kayaku Co.,Ltd.
Not Provided
Principal Investigator: David Jayne Addenbrookes Hospital
Nippon Kayaku Co.,Ltd.
September 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP