Phase II Study on Gusperimus in Patients With Refractory Wegener's Granulomatosis
Condition: Wegener's Granulomatosis
MeSH terms: Granulomatosis with Polyangiitis
Intervention: Gusperimus
Intervention description: SC, 0.5mg/kg/day, consecutive 21 days administration, 1 to 2 weeks rest, 6 cycles
Intervention MeSH terms: Gusperimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Wegener Granulomatosis; Vasculitis; Gusperimus; Immunosuppression

Summary:

      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      Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to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.
    

Eligibility 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