Clinical Study Comparing the New Immunosuppressive Drug Gusperimus With the Conventional Treatment in Wegener's Granulomatosis (SPARROW)

• Response rate [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

  The primary efficacy variable is the rate of patients showing a response, with the level of disease activity Birmingham Vasculitis Activity Score (BVAS) ≤ 2, within 24 weeks of trial entry, which is maintained without relapse until the end of the trial (Week 52).

  The primary efficacy endpoint includes:

  i) Remission - defined as the complete absence of active clinical disease, i.e. a BVAS score of 0, for at least two months on a stable prednisone dose of ≤ 10 mg/day.

  ii) Low activity Disease State - persistence of up to two minor BVAS items (BVAS ≤ 2).

  
  

• Time to response [ Time Frame: From the date of study entry until the first occasion that BVAS is ≤ 2, assessed up to 52 weeks ] [ Designated as safety issue: No ]
  Time to response (response is defined as the time from study entry to the first occasion that BVAS is ≤ 2, and there has been adherence to the steroid reduction protocol)
  
  
• Response duration [ Time Frame: From the date of response with BVAS≤2 until relapse, assessed up to 48 weeks ] [ Designated as safety issue: No ]
  Response duration defined as time from response with BVAS≤2 to relapse (relapse is defined as the return or first occurrence of one major and/or three minor BVAS items)
  
  
• Frequency of severe relapses [ Time Frame: Up to 52 weeks ] [ Designated as safety issue: No ]
  Frequency of severe relapses (defined as at least one major BVAS item)
  
  
• Vasculitis Damage Index (VDI) score change [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  VDI score change from baseline to month 12
  
  
• Glomerular Filtration Rate (eGFR) change [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  eGFR change from baseline to month 12 in all patients and in a subgroup defined as having a baseline eGFR ≤ 60mL/min (i.e. renal impairment at baseline)
  
  
• Frequency of Adverse Events (AEs) and Serious Adverse Event (SAEs) [ Time Frame: Up to 52 weeks ] [ Designated as safety issue: Yes ]
  Frequency of AEs and SAEs. (Total number of AEs per group according to AE category) (Percentage of patients in each group with a severe AE)
  
  
• Frequency of severe infection [ Time Frame: Up to 52 weeks ] [ Designated as safety issue: Yes ]
  Frequency of severe infection (a severe infection is defined as an infection that requires intravenous antibiotics or hospitalisation).(Percentage of patients in each group with a severe infection)
  
  
• Pharmacokinetic parameters at selected sites [ Time Frame: 1st day of gusperimus cycles 1, 6 or 7, 12 or 13 ] [ Designated as safety issue: No ]
  Pharmacokinetic parameters Area Under the plasmaconcentration - time Curve (AUC), Maximum concentration reached in plasma (Cmax), Time to maximum concentration reached in plasma (Tmax) and Elimination half life in plasma (T½) calculated from the measured plasma samples collected at regular time intervals after administration of gusperimus on the first day of three treatment cycles
  
  
• Short-Form-36 (SF-36) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  Pooled physical and mental SF-36 domains change from baseline to month 6
  
  
• Short-Form-36 (SF-36) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Pooled physical and mental SF-36 domains change from baseline to month 12
  
  
• Total corticosteroid exposure [ Time Frame: Up to 52 weeks ] [ Designated as safety issue: No ]
  The total corticosteroid exposure
  
  
• Questionnaire EQ-5D [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  Change in EQ-5D between baseline and month 12
  
  
• Frequency of non-severe relapses [ Time Frame: Up to 52 weeks ] [ Designated as safety issue: No ]
  Frequency of non-severe relapses (defined as at least 3 minor BVAS items with no major BVAS items).
  
  

Wegener Granulomatosis without treatment is life-threatening. The standard treatment with corticosteroids and cyclophosphamide is usually effective at controlling active disease. However, disease relapse is frequent and requires increased exposure to these toxic drugs. In other patients initiation or continuation of these standard drugs is contraindicated due to intolerable side effects. No well-established therapy is available for relapsing patients. They may suffer severe organ damage due to progressive disease, or may die. The proposed indication for gusperimus is the treatment of relapsing Wegener Granulomatosis. The aim of therapy with gusperimus is to induce and maintain remission thereby avoiding further cyclophosphamide and reducing corticosteroid exposure.