Clinical Study Comparing the New Immunosuppressive Drug Gusperimus With the Conventional Treatment in Wegener's Granulomatosis
Clinical Study Comparing the New Immunosuppressive Drug Gusperimus With the Conventional Treatment in Wegener's Granulomatosis
The aim of the study is to assess the efficacy (superiority testing) of gusperimus compared
 to conventional treatment in patients with a relapse of Wegener Granulomatosis with or
 without ongoing steroids, and/or immunosuppressive therapy. Further, to evaluate the safety
 and quality of life of gusperimus treatment compared to standard treatment in patients with
 relapse of Wegener Granulomatosis receiving glucocorticoids.
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.
Inclusion Criteria:

 1. Documented diagnosis of Wegener's Granulomatosis (WG) according to the American
 College of Rheumatology classification criteria.

 2. Diagnosis of WG at least 6 months before entry and initial induction therapy with a
 combination of Glucocorticoids and an immunosuppressive (Cyclophosphamide or
 Methotrexate) or rituximab.

 3. Relapse of WG with or without ongoing Glucocorticoids, and/or immunosuppressive
 therapy with Azathioprine/Mycophenolate Mofetil/Methotrexate or Leflunomide. The
 minimum disease activity is defined by the presence of one new/worse major or three
 new/worse minor BVAS (version 3) items.

 4. Patients between 18 - 75 years.

 5. Medically acceptable and reliable contraception method during the study course. (Women
 should not become pregnant for at least 6 months after Cyclophosphamide treatment).

 6. Written informed consent for study participation given by the patient.

 7. Patients able and prepared to self-administer the study medication or having a
 relative/third person able to do it.

 8. Ability to read, understand and record information required by protocol

 Exclusion Criteria:

 1. Other multi-system autoimmune disorders, including systemic lupus erythematosus and
 anti-Glomerular Basement Membrane disease.

 2. Systemic vasculitis due to a viral infection.

 3. Cyclophosphamide therapy intolerance, hypersensitivity or contraindication to
 Cyclophosphamide (active substance or any of the excipients) in patients with severe
 relapse of WG.

 4. Hypersensitivity or contraindication to

 -  Spanidin (active substance or any of the excipients) or

 -  both Methotrexate (active substance or any of the excipients) and
 Azathioprine(active substance or any of the excipients) or

 -  methylprednisolone, prednisolone or other corticosteroids (active substance or
 any of the excipients).

 5. Underlying medical conditions, which in the opinion of the Investigator place the
 patient at an unacceptable risk level for participating in a study.

 6. Previous randomisation in this study.

 7. Cyclophosphamide , intravenous immunoglobulin, anti-cytokine biologic therapies,
 plasma exchange or Abatacept in the three months prior to entry to the trial.
 Rituximab, Alemtuzumab or stem cell transplantation is not permitted in the six months
 prior to entry to the trial.

 8. Previous treatment with gusperimus.

 9. Participation in another clinical trial with investigational drugs within the last 3
 months before screening or during the present trial period.

 10. Pregnant or breast-feeding females.

 11. Active bacterial/viral infection (Human Immunodeficiency Virus, Hepatitis B, Hepatitis
 C, Tuberculosis).

 12. Patients with Glomerular Filtration Rate (eGFR) < 15 mL/min/1.73m2.

 13. Alanine transaminase (ALT), Aspartate aminotransferase (AST), bilirubin, and Alkaline
 phosphatase (ALP) levels above 2 x the upper normal limit.

 14. Inadequate bone-marrow function: White Blood Cells (WBC) < 4000/mm3, haemoglobin < 8
 g/dL, neutrophils < 2500/mm3, platelets < 100 000/mm3.