Phase II Study on Gusperimus in Patients With Refractory Wegener's Granulomatosis

Wegener's Granulomatosis Clinical Trial

Official title:

Phase II Study on Gusperimus in Patients With Refractory Wegener's Granulomatosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00530075
• Other study ID #: 102
• Status: Completed
• Phase: Phase 2
• First received: September 14, 2007
• Last updated: February 13, 2008
• Start date: December 2003
• Est. completion date: February 2006

Study information

• Verified date: September 2007
• Source: Nippon Kayaku Co.,Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyCzech Republic: State Institute for Drug ControlDenmark: Danish Medicines AgencyGermany: Federal Institute for Drugs and Medical DevicesNetherlands: Medicines Evaluation BoardSweden: Medical Products Agency
• Study type: Interventional

Clinical Trial 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 Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status.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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: February 2006
• Est. primary completion date: February 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Wegener Granulomatosis
• Wegener's Granulomatosis

Intervention

Drug:
• Gusperimus
SC, 0.5mg/kg/day, consecutive 21 days administration, 1 to 2 weeks rest, 6 cycles

Locations

Country	Name	City	State
Czech Republic	General Faculty Hospital	Prague
Denmark	Reumatologisk Klinik	Copenhagen
Germany	Universitatsklinikum Schleswig-Holstein	Luebeck
Netherlands	University Hospital Maastricht	Maastricht
Sweden	Karolinska University Hospital	Stockholm
United Kingdom	Addenbrookes Hospital	Cambridge
United Kingdom	Western General Hospital	Edinburgh	Scotland

Sponsors (1)

Lead Sponsor	Collaborator
Nippon Kayaku Co.,Ltd.

Countries where clinical trial is conducted

Czech Republic,  Denmark,  Germany,  Netherlands,  Sweden,  United Kingdom, 

References & Publications (1)

Birck R, Warnatz K, Lorenz HM, Choi M, Haubitz M, Grünke M, Peter HH, Kalden JR, Göbel U, Drexler JM, Hotta O, Nowack R, Van Der Woude FJ. 15-Deoxyspergualin in patients with refractory ANCA-associated systemic vasculitis: a six-month open-label trial to evaluate safety and efficacy. J Am Soc Nephrol. 2003 Feb;14(2):440-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Remission (defined by Birmingham Vasculitis Activity Score (BVAS))		Screening, Day1 of Cycle1, End of each cycle	No
Secondary	Duration of clinical response, Laboratory markers (CRP, ESR, urine-analysis, ANCA), Damage as measured by the Vasculitis Damage Index, Patient function as measured by the SF-36 score, Adverse events		Screening, Day1 of Cycle1, End of each cycle; for Adverse events, throughaout study period	Yes

External Links

•   The European Vasculitis Study Group