Safety and Efficacy Study of Fostamatinib to Treat Immunoglobin A (IgA) Nephropathy
- Conditions
- IGA Nephropathy
- Interventions
- Registration Number
- NCT02112838
- Lead Sponsor
- Rigel Pharmaceuticals
- Brief Summary
The purpose of this study is to determine whether fostamatinib is safe and effective in the treatment of IgA Nephropathy
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 76
- Renal biopsy findings consistent with IgA nephropathy
- Treatment with an Angiotensin Converting Enzyme inhibitor (ACEi) and/or an Angiotensin II Receptor Blocker (ARB) for at least 90 days at the maximum approved (or tolerated) dose
- Proteinuria > 1 gm/day at diagnosis of IgA nephropathy and Proteinuria > 0.50 gm/day at the second Screening Visit
- Blood pressure controlled to ≤ 130/80 with angiotensin blockade with or without other anti-hypertensive agents
- Recent use of cyclophosphamide, mycophenolate mofetil, azathioprine, or Rituximab.
- Use of > 15 mg/day prednisone (or other corticosteroid equivalent).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Fostamatinib 150 mg Fostamatinib 150 mg Fostamatinib 150 milligram (mg) tablet twice daily by mouth, over the course of 24 weeks Fostamatinib 100 mg Fostamatinib 100 mg Fostamatinib 100 mg tablet twice daily by mouth, over the course of 24 weeks Placebo Placebo Placebo tablet twice daily by mouth, over the course of 24 weeks
- Primary Outcome Measures
Name Time Method Mean Change of Proteinuria as Measured by Spot Urine Protein/Creatinine Ratio (sPCR) at Week 24 Baseline to 24 weeks Mean change from Baseline (Visit 2) of proteinuria as measured by the spot Protein-Creatinine Ratio (sPCR) at 24 weeks (Visit 9) for the ITT Population
- Secondary Outcome Measures
Name Time Method Mean Change From Pre-treatment to Post-treatment in Mesangial Hypercellularity (M) on Renal Biopsies. Baseline to Week 24 Mean change from pre-treatment to post-treatment in mesangial hypercellularity on renal biopsies. Using the Oxford Classification of IgA Nepthropathy (IgAN), biopsy specimens with a minimum of 8 glomeruli, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), and interstitial fibrosis/tubular atrophy (T) lesions are scored for assessing histologic findings in IgAN.
M = the mean score based on Oxford Classification system score is based on total count of mesangial cells for all glomeruli (count of \<4=0 score, 4 to 5=1, 6 to 7=2, ≥8=3). A decrease in score equates to improvement from IgAN disease.Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Segmental Sclerosis/Adhesion (S) on Renal Biopsies. Baseline to Week 24 Mean change from pre-treatment to post-treatment in mesangial hypercellularity on renal biopsies. Using the Oxford Classification of IgA Nepthropathy (IgAN), biopsy specimens with a minimum of 8 glomeruli, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), and interstitial fibrosis/tubular atrophy (T) lesions are scored for assessing histologic findings in IgAN.
S = Percentage of any amount of the tuft involved in sclerosis, but not involving the whole tuft or the presence of an adhesion in each glomeruli. A decrease in score equates to improvement from IgAN disease.Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Global Glomerulosclerosis Score on Renal Biopsies. Baseline to Week 24 Mean change from pre-treatment to post-treatment in mesangial hypercellularity on renal biopsies. Using the Oxford Classification of IgA Nepthropathy (IgAN), biopsy specimens with a minimum of 8 glomeruli, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), and interstitial fibrosis/tubular atrophy (T) lesions are scored for assessing histologic findings in IgAN.
Percentage of any amount of the tuft involved in sclerosis, but not involving the whole tuft or the presence of an adhesion in each glomeruli. A decrease in score equates to improvement from IgAN disease.Percentage of Subjects With ≥ 30% Reduction in Proteinuria From Baseline (Visit 2) at 24 Weeks (Visit 9). Baseline to Week 24 Percentage of subjects with ≥ 30% reduction in proteinuria from Baseline (Visit 2) at 24 weeks (Visit 9).
Percentage of Subjects With ≥50% Reduction in sPCR From Baseline (Visit 2) at Week 24 (Visit 9). Baseline to Week 24 Percentage of subjects with ≥50% reduction in sPCR from Baseline (Visit 2) at Week 24 (Visit 9)
Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Endocapillary Hypercellularity (E) on Renal Biopsies. Baseline to Week 24 Mean change from pre-treatment to post-treatment in mesangial hypercellularity on renal biopsies. Using the Oxford Classification of IgA Nepthropathy (IgAN), biopsy specimens with a minimum of 8 glomeruli, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), and interstitial fibrosis/tubular atrophy (T) lesions are scored for assessing histologic findings in IgAN.
E = Percentage of glomeruli eypercellularity due to increased number of cells within glomerular capillary lumina causing narrowing of the lumina. A decrease in score equates to improvement from IgAN disease.Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Tubulointerstitial Scarring (T) on Renal Biopsies. Baseline to Week 24 Mean change from pre-treatment to post-treatment in mesangial hypercellularity on renal biopsies. Using the Oxford Classification of IgA Nepthropathy (IgAN), biopsy specimens with a minimum of 8 glomeruli, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), and interstitial fibrosis/tubular atrophy (T) lesions are scored for assessing histologic findings in IgAN.
T= Percentage of cortical area involved by the tubular atrophy or interstitial fibrosis, whichever is greater. A decrease in score equates to improvement from IgAN disease.Mean Change From Baseline (Visit 2) of Proteinuria at 12 Weeks (Visit 7). Baseline to Week 12 Mean change from Baseline (Visit 2) of proteinuria at 12 weeks (Visit 7).
Percentage of Subjects With sPCR <50 mg/mmol (500 mg/g) at 12 Weeks (Visit 7). Baseline to Week 12 Percentage of subjects with sPCR \<50 mg/mmol (500 mg/g) at 12 weeks (Visit 7).
Shift in Haematuria (Dipstick Test) From Baseline (Visit 2) at 12 Weeks (Visit 7). Baseline to Week 12 Shift in haematuria (dipstick test) from Baseline (Visit 2) at 12 weeks (Visit 7).
Shift in Haematuria (Dipstick Test) From Baseline (Visit 2) at 24 Weeks (Visit 9). Baseline to Week 24 Shift in haematuria (dipstick test) from Baseline (Visit 2) at 24 weeks (Visit 9).
Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Cellular/Fibrocellular Crescent Score on Renal Biopsies. Baseline to Week 24 Mean change from pre-treatment to post-treatment in cellular/fibrocellular crescent score on renal biopsies. Biopsy specimens with a minimum of 8 glomeruli, mesangial hypercellularity (M), segmental sclerosis (S), and interstitial fibrosis/tubular atrophy (T) lesions are scored using the Oxford Classification of IgA nepthropathy (IgAN) system for assessing histologic findings in IgAN.
Mean Change From Baseline (Visit 2) of eGFR at 12 Weeks (Visit 7). Baseline to Week 12 Mean change from Baseline (Visit 2) of eGFR at 12 weeks (Visit 7).
Mean Change From Baseline (Visit 2) of eGFR at 24 Weeks (Visit 9). Baseline to Week 24 Mean change from Baseline (Visit 2) of eGFR at 24 weeks (Visit 9).
Trial Locations
- Locations (20)
Southeast Renal Research Institute
🇺🇸Chattanooga, Tennessee, United States
Medical University Vienna, Nephrology
🇦🇹Vienna, Austria
China Medical University Hospital
🇨🇳Taichung, Taiwan
Medical University of Jena
🇩🇪Jena, Thueringen, Germany
Klinikum der Universität München
🇩🇪Munich, Bayern, Germany
Stanford University Medical
🇺🇸Palo Alto, California, United States
Nephrology Associates PC, University Hospital, Professional Center 1
🇺🇸Augusta, Georgia, United States
Addenbrookes Hospital
🇬🇧Cambridge, United Kingdom
Royal Free Hospital
🇬🇧London, United Kingdom
Medical University of Graz
🇦🇹Graz, Steiermark, Austria
Medical University of Heidelberg
🇩🇪Heidelberg, Baden-Wurtemberberg, Germany
School of Medicine, Chang Gung University, Chang Gung Memorial Hospital
🇨🇳Taoyuan, Taiwan
Leicester General Hospital
🇬🇧Leicester, United Kingdom
Cardiff University
🇬🇧Cardiff, United Kingdom
Hammersmith Hospital
🇬🇧London, United Kingdom
Freeman Hospital
🇬🇧Newcastle upon Tyne, United Kingdom
Ohio State University
🇺🇸Columbus, Ohio, United States
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
🇩🇪Dresden, Sachsen, Germany
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Prince of Wales Hospital
🇭🇰Hong Kong, Sha Tin, Hong Kong