Clinical Study Comparing the New Immunosuppressive Drug Gusperimus With the Conventional Treatment in Wegener's Granulomatosis (SPARROW)
|Wegeners Granulomatosis||Drug: Gusperimus + glucocorticoids Drug: cyclophosphamide followed by methotrexate (azathioprine) + glucocorticoids or methotrexate (azathioprine) + glucocorticoids||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Randomised, Evaluator-Blinded, Multicentre, International, Parallel-Group, Active-Controlled Clinical Trial of Gusperimus Versus Conventional Therapy in Relapse of Granulomatosis With Polyangiitis (Wegener's Granulomatosis) SPARROW Study - SPAnidin in Relapsing GRanulomatosis With POlyangiitis Wegener's Granulomatosis)|
- Response rate [ Time Frame: 52 weeks ]
The primary efficacy variable is the rate of patients showing a response, with the level of disease activity Birmingham Vasculitis Activity Score (BVAS) ≤ 2, within 24 weeks of trial entry, which is maintained without relapse until the end of the trial (Week 52).
The primary efficacy endpoint includes:
i) Remission - defined as the complete absence of active clinical disease, i.e. a BVAS score of 0, for at least two months on a stable prednisone dose of ≤ 10 mg/day.
ii) Low activity Disease State - persistence of up to two minor BVAS items (BVAS ≤ 2).
- Time to response [ Time Frame: From the date of study entry until the first occasion that BVAS is ≤ 2, assessed up to 52 weeks ]Time to response (response is defined as the time from study entry to the first occasion that BVAS is ≤ 2, and there has been adherence to the steroid reduction protocol)
- Response duration [ Time Frame: From the date of response with BVAS≤2 until relapse, assessed up to 48 weeks ]Response duration defined as time from response with BVAS≤2 to relapse (relapse is defined as the return or first occurrence of one major and/or three minor BVAS items)
- Frequency of severe relapses [ Time Frame: Up to 52 weeks ]Frequency of severe relapses (defined as at least one major BVAS item)
- Vasculitis Damage Index (VDI) score change [ Time Frame: 12 months ]VDI score change from baseline to month 12
- Glomerular Filtration Rate (eGFR) change [ Time Frame: 12 months ]eGFR change from baseline to month 12 in all patients and in a subgroup defined as having a baseline eGFR ≤ 60mL/min (i.e. renal impairment at baseline)
- Frequency of Adverse Events (AEs) and Serious Adverse Event (SAEs) [ Time Frame: Up to 52 weeks ]Frequency of AEs and SAEs. (Total number of AEs per group according to AE category) (Percentage of patients in each group with a severe AE)
- Frequency of severe infection [ Time Frame: Up to 52 weeks ]Frequency of severe infection (a severe infection is defined as an infection that requires intravenous antibiotics or hospitalisation).(Percentage of patients in each group with a severe infection)
- Pharmacokinetic parameters at selected sites [ Time Frame: 1st day of gusperimus cycles 1, 6 or 7, 12 or 13 ]Pharmacokinetic parameters Area Under the plasmaconcentration - time Curve (AUC), Maximum concentration reached in plasma (Cmax), Time to maximum concentration reached in plasma (Tmax) and Elimination half life in plasma (T½) calculated from the measured plasma samples collected at regular time intervals after administration of gusperimus on the first day of three treatment cycles
- Short-Form-36 (SF-36) [ Time Frame: 6 months ]Pooled physical and mental SF-36 domains change from baseline to month 6
- Short-Form-36 (SF-36) [ Time Frame: 12 months ]Pooled physical and mental SF-36 domains change from baseline to month 12
- Total corticosteroid exposure [ Time Frame: Up to 52 weeks ]The total corticosteroid exposure
- Questionnaire EQ-5D [ Time Frame: 12 months ]Change in EQ-5D between baseline and month 12
- Frequency of non-severe relapses [ Time Frame: Up to 52 weeks ]Frequency of non-severe relapses (defined as at least 3 minor BVAS items with no major BVAS items).
|Study Start Date:||November 2011|
|Study Completion Date:||January 2015|
|Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Experimental: Test group - gusperimus
Both severity subgroups (severe and non-severe) will be treated with gusperimus + glucocorticoids.
Drug: Gusperimus + glucocorticoids
Both severity subgroups will be treated with gusperimus + glucocorticoids up to 12 months.
Active Comparator: Control group
The severe subgroup will receive a course (13 - 22 weeks) of cyclophosphamide followed by methotrexate + glucocorticoids. Patients intolerant to methotrexate and patients with impaired renal function will receive azathioprine + glucocorticoids.
The non-severe subgroup will receive methotrexate + glucocorticoids(or azathioprine + glucocorticoids for those previously intolerant to methotrexate or with impaired renal function).
Drug: cyclophosphamide followed by methotrexate (azathioprine) + glucocorticoids or methotrexate (azathioprine) + glucocorticoids
Severe subgroup: will receive intravenous cyclophosphamide pulses for at least 13 weeks and 22 weeks at maximum, followed by methotrexate + glucocorticoids after achieving a response with BVAS ≤ 2. Patients intolerant to methotrexate and patients with impaired renal function will receive azathioprine + glucocorticoids .
Non-severe subgroup: will receive methotrexate + glucocorticoids (or azathioprine + glucocorticoids for those previously intolerant to methotrexate or with impaired renal function).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01446211
|Všeobecná fakultní nemocnice v Praze|
|Praha, Czech Republic, 128 08|
|Principal Investigator:||David Jayne, MD||Addenbrookes Hospital, Cambridge, United Kingdom|