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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 Immunosuppressive drugs were withdrawn at entry and prednisolone doses adjusted according to clinical status.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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | Gusperimus |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Gusperimus | Drug | SC, 0.5mg/kg/day, consecutive 21 days administration, 1 to 2 weeks rest, 6 cycles |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Duration of Clinical Response | Time from Complete Remission or Partial Remission to Relapse. | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David Jayne | Cambridge University Hospitals NHS Foundation Trust | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| General Faculty Hospital | Prague | 12808 | Czechia | |||
| Reumatologisk Klinik |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12538745 | Background | 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. |
| Label | URL |
|---|---|
| The European Vasculitis Study Group | View source |
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The study was conducted at 7 sites in 6 European countries from 2003 to 2006
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| ID | Title | Description |
|---|---|---|
| FG000 | Gusperimus | SC, 0.5mg/kg/day, consecutive 21 days administration, 7 days rest, 6 cycles |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Gusperimus | SC, 0.5mg/kg/day, consecutive 21 days administration, 7 days rest, 6 cycles |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Efficacy Population | Posted | Number | Percentage of participants | At Entry (Day 1 of Cycle 1), Day 22 of cycles 1-6, up to 24 weeks |
|
Throughout study period, up to 24 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Gusperimus | SC, 0.5mg/kg/day, consecutive 21 days administration, 7 days rest, 6 cycles |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leucopaenia/Anaemia | Blood and lymphatic system disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pharmaceuticals Group | Nippon Kayaku Co., Ltd. | +81-3-6731-5200 |
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| ID | Term |
|---|---|
| D014890 | Granulomatosis with Polyangiitis |
| D014657 | Vasculitis |
| ID | Term |
|---|---|
| D017563 | Lung Diseases, Interstitial |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D056648 | Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis |
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| ID | Term |
|---|---|
| C037258 | gusperimus |
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Assessment of anti-inflammatory activity of gusperimus using surrogate marker: number of hematuria-positive patients.
| At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks |
| Creatinine | Assessment of anti-inflammatory activity of gusperimus using surrogate marker: serum creatinine level | At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks |
| ANCA | 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. | At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks |
| CRP | Assessment of anti-inflammatory activity of gusperimus using surrogate marker: serum C-reactive protein level. | At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks |
| Vasculitis Damage Index (VDI) | 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. | At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks, 6 months of follow-up period |
| SF-36 | 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. | At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks |
| Copenhagen |
| 2100 |
| Denmark |
| Universitatsklinikum Schleswig-Holstein | Lübeck | 23538 | Germany |
| University Hospital Maastricht | Maastricht | 6202 | Netherlands |
| Karolinska University Hospital | Stockholm | 14186 | Sweden |
| Western General Hospital | Edinburgh | Scotland | EH4 2XU | United Kingdom |
| Addenbrookes Hospital | Cambridge | CB2 2QQ | United Kingdom |
| Protocol Violation |
|
| Withdrawal by Subject |
|
| Years |
|
| Gender | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | Duration of Clinical Response | Time from Complete Remission or Partial Remission to Relapse. | Patients who had relapsed after achieved at least partial remission | Posted | Median | Full Range | Days | 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 |
|
|
|
| Secondary | Haematuria | Assessment of anti-inflammatory activity of gusperimus using surrogate marker: number of hematuria-positive patients. | Efficacy population | Posted | Number | Number of participants | At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks |
|
|
|
| Secondary | Creatinine | Assessment of anti-inflammatory activity of gusperimus using surrogate marker: serum creatinine level | Efficacy population | Posted | Median | Full Range | micromol/L | At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks |
|
|
|
| Secondary | ANCA | 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. | Efficacy Population | Posted | Number | Number of participants | At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks |
|
|
|
| Secondary | CRP | Assessment of anti-inflammatory activity of gusperimus using surrogate marker: serum C-reactive protein level. | Patients who had elevated CRP level (> 6 mg/dL) at entry | Posted | Median | Full Range | mg/dL | At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks |
|
|
|
| Secondary | Vasculitis Damage Index (VDI) | 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. | Efficacy Population | Posted | Median | Full Range | Score on a scale | At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks, 6 months of follow-up period |
|
|
|
| Secondary | SF-36 | 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. | Efficacy Population | Posted | Median | Full Range | Score on a scale | At Entry (Day 1 of Cycle 1), End of treatment period, up to 24 weeks |
|
|
|
| 17 |
| 45 |
| 45 |
| 45 |
| Infections | Infections and infestations |
|
| Bronchopneumonia | Infections and infestations |
|
| Dental abscess | Infections and infestations |
|
| Campylobacter jejuni diarrhoea | Infections and infestations |
|
| Relapses of Wegener's granulomatosis | Respiratory, thoracic and mediastinal disorders |
|
| Acute upper airway obstruction | Respiratory, thoracic and mediastinal disorders |
|
| Active Wegener's granulomatosis | Respiratory, thoracic and mediastinal disorders |
|
| Food poisoning | Gastrointestinal disorders |
|
| Diarrhoea | Gastrointestinal disorders |
|
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| Leucopaenia | Blood and lymphatic system disorders |
|
| Lower respiratory tract infection | Infections and infestations |
|
| Upper respiratory tract infection | Infections and infestations |
|
| Urinary tract infection | Infections and infestations |
|
| Candida infection | Infections and infestations |
|
| Injection site pain/pruritus | General disorders |
|
| Injection site haemorrhage | General disorders |
|
| Pain oral cavity/throat | Gastrointestinal disorders |
|
| Dysgeusia | Nervous system disorders |
|
| Stomatitis/mouth ulcers | Gastrointestinal disorders |
|
| Abdominal pain | Gastrointestinal disorders |
|
| Anorexia | Metabolism and nutrition disorders |
|
| Diarrhoea | Gastrointestinal disorders |
|
| Nausea | Gastrointestinal disorders |
|
| Vomoting | Gastrointestinal disorders |
|
| Fatigue | General disorders |
|
| Acne | Skin and subcutaneous tissue disorders |
|
| Alopecia | Skin and subcutaneous tissue disorders |
|
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| D056647 | Systemic Vasculitis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| Title | Measurements |
|---|---|
|
|
| Mental component score (at End of treatment period |
|