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Completed

NCT Number: NCT00530075

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

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 Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status.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

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Key information

Conditions

Wegener's Granulomatosis Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis Autoimmune Diseases Cardiovascular Diseases Granulomatosis with Polyangiitis Immune System Diseases Lung Diseases Lung Diseases, Interstitial Respiratory Tract Diseases Skin Diseases Skin Diseases, Vascular Skin and Connective Tissue Diseases Systemic Vasculitis Vascular Diseases Vasculitis

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

General Faculty Hospital, Prague, Czechia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Gusperimus

Drug

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

Primary outcomes

  1. Remission of Vasculitis

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

    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.

Secondary outcomes

  1. Duration of Clinical Response

    Time frame: 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

    Time from Complete Remission or Partial Remission to Relapse.

  2. Haematuria

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

    Assessment of anti-inflammatory activity of gusperimus using surrogate marker: number of hematuria-positive patients.

  3. Creatinine

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

    Assessment of anti-inflammatory activity of gusperimus using surrogate marker: serum creatinine level

  4. ANCA

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

    Assessment of anti-neutrophil cytoplasmic antibody (ANCA): Number of ANCA-positive patients was counted.

    ANCA are highly associatred with active WG, with c-ANCA titres observed in 90% of WG. In addition to their diagnostic value, it has been suggested that ANCA may have a predictive value for relapse in patients with systemic vasculitis.

  5. CRP

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

    Assessment of anti-inflammatory activity of gusperimus using surrogate marker: serum C-reactive protein level.

  6. Vasculitis Damage Index (VDI)

    Time frame: At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks, 6 months of follow-up period

    Assessment of the degree of irreversible damage due to the vasculitis using VDI scoring system. The VDI comprises 64 items of damage (grouped into 11 organ-based systems). Total VDI score is 0 - 64. The higher scores represent the more severe damage occurred in patients. The VDI score can either increase or remain the same over time.

  7. SF-36

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

    Assessment of the impact of gusperimus on general health using the Short form-36 (SF-36) questionaire. The SF-36 is a self-report, 36 item survey measuring health-related quality-of-life. Thirty-five items are used to construct 8 scales: (1) physical functioning, (2) role physical, (3) bodily pain, (4) general health, (5) vitality, (6) social function, (7) role emotional, and (8) mental health. Raw scores are calculated as the sum of re-coded scale items and transformed to a 0 to 100 scale. If scores for all 8 scales are available, two summary measures known as component scores are derived: the Physical Health Component Score (PCS) and the Mental Health Component Score (MCS). First each scale standardized to the relevant population. Then PCS and MCS are calculated as the weighted sum of standardized scores. All scales and the component scores are positively scored so that higher scores represent better health-related quality-of-life.

Sponsors and collaborators

Lead sponsor

Nippon Kayaku Co., Ltd.

Industry

Registry information

Important dates

Study start
2003
Primary completion
2006
Study completion
2006
First posted
Sep 17, 2007
Registry last updated
Mar 6, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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