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.

Eligibility Criteria:
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.