Clinical trial NCT00530075: Phase II Study on Gusperimus in Patients With Refractory Wegener's Granulomatosis
Official title: Phase II Study on Gusperimus in Patients With Refractory Wegener's Granulomatosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Wegener's Granulomatosis
Keywords: Wegener Granulomatosis
Vasculitis
Gusperimus
Immunosuppression
Lead sponsor: Nippon Kayaku Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2007-09-17
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status.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

Primary outcomes:
measure: Remission of Vasculitis
timeFrame: At Entry (Day 1 of Cycle 1), Day 22 of cycles 1-6, up to 24 weeks
Secondary outcomes:
measure: Duration of Clinical Response
timeFrame: At Entry (Day 1 of Cycle 1), Day 22 of cycles 1-6, up to 24 weeks, End of treatment period, and 3 and 6 months of follow-up period
measure: Haematuria
timeFrame: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks
measure: Creatinine
timeFrame: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks
measure: ANCA
timeFrame: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks
measure: CRP
timeFrame: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks
measure: Vasculitis Damage Index (VDI)
timeFrame: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks, 6 months of follow-up period
measure: SF-36
timeFrame: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks
Other outcomes:
Locations:
city: Prague
country: Czech Republic
facility: General Faculty Hospital
city: Copenhagen
country: Denmark
facility: Reumatologisk Klinik
city: Luebeck
country: Germany
facility: Universitatsklinikum Schleswig-Holstein
city: Maastricht
country: Netherlands
facility: University Hospital Maastricht
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
state: Scotland
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
Study officials:
affiliation: Cambridge University Hospitals NHS Foundation Trust
name: David Jayne
role: PRINCIPAL_INVESTIGATOR
References:
citation: Birck R, Warnatz K, Lorenz HM, Choi M, Haubitz M, Grunke M, Peter HH, Kalden JR, Gobel 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. doi: 10.1097/01.asn.0000048716.42876.14.