NCT00530075

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 Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status.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

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
45

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Dec 2003

Geographic Reach
6 countries

7 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2003

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2006

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2006

Completed
1.6 years until next milestone

First Submitted

Initial submission to the registry

September 14, 2007

Completed
3 days until next milestone

First Posted

Study publicly available on registry

September 17, 2007

Completed
9.5 years until next milestone

Results Posted

Study results publicly available

March 6, 2017

Completed
Last Updated

March 6, 2017

Status Verified

September 1, 2007

Enrollment Period

2.2 years

First QC Date

September 14, 2007

Results QC Date

April 18, 2016

Last Update Submit

January 16, 2017

Conditions

Wegener's Granulomatosis

Keywords

Wegener GranulomatosisVasculitisGusperimusImmunosuppression

Outcome Measures

Primary Outcomes (1)

  • Remission of Vasculitis

    The primary efficacy outcome measure was remission of vasculitis. Complete remission was defined as a Birmingham vasculitis activity score (BVAS) of 0 sustained for at least 2 months. Partial remission was defined as a reduction in BVAS of 50% or more, sustained for at least 2 months, when compared with the BVAS at entry. Entry required active Wegener's granulomatosis with a BVAS \>= 4. Their disease had to be active, as measured with BVAS in which clinical manifestations caused by active vasculitis are scored on a list of predefined organ-specific items.

    At Entry (Day 1 of Cycle 1), Day 22 of cycles 1-6, up to 24 weeks

Secondary Outcomes (7)

  • Duration of Clinical Response

    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

  • Haematuria

    At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks

  • Creatinine

    At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks

  • ANCA

    At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks

  • CRP

    At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks

  • +2 more secondary outcomes

Study Arms (1)

1

EXPERIMENTAL

Gusperimus

Drug: Gusperimus

Interventions

GusperimusDRUG

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

1

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

General Faculty Hospital

Prague, 12808, Czechia

Location

Reumatologisk Klinik

Copenhagen, 2100, Denmark

Location

Universitatsklinikum Schleswig-Holstein

Lübeck, 23538, Germany

Location

University Hospital Maastricht

Maastricht, 6202, Netherlands

Location

Karolinska University Hospital

Stockholm, 14186, Sweden

Location

Western General Hospital

Edinburgh, Scotland, EH4 2XU, United Kingdom

Location

Addenbrookes Hospital

Cambridge, CB2 2QQ, United Kingdom

Location

Related Publications (1)

  • 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.

    PMID: 12538745BACKGROUND

Related Links

MeSH Terms

Conditions

Granulomatosis with PolyangiitisVasculitis

Interventions

gusperimus

Condition Hierarchy (Ancestors)

Lung Diseases, InterstitialLung DiseasesRespiratory Tract DiseasesAnti-Neutrophil Cytoplasmic Antibody-Associated VasculitisSystemic VasculitisVascular DiseasesCardiovascular DiseasesSkin Diseases, VascularSkin DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System Diseases

Results Point of Contact

Title
Pharmaceuticals Group
Organization
Nippon Kayaku Co., Ltd.
+81-3-6731-5200

Study Officials

  • David Jayne

    Cambridge University Hospitals NHS Foundation Trust

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY

Study Record Dates

First Submitted

September 14, 2007

First Posted

September 17, 2007

Study Start

December 1, 2003

Primary Completion

February 1, 2006

Study Completion

February 1, 2006

Last Updated

March 6, 2017

Results First Posted

March 6, 2017

Record last verified: 2007-09

Locations

CZ(1)DK(1)DE(1)GB(2)SE(1)NL(1)