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 Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to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