Safety and Efficacy Study of Fostamatinib to Treat Immunoglobin A (IgA) Nephropathy

Study Overview
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Brief Summary
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The purpose of this study is to determine whether fostamatinib is safe and effective in the treatment of IgA Nephropathy

Official Title
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A Phase 2, Multi-Center, Randomised, Double-Blind, Ascending-Dose, Placebo-Controlled Clinical Study to Assess the Safety and Efficacy of Fostamatinib in the Treatment of IgA Nephropathy

Conditions
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IGA Nephropathy

Intervention / Treatment
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* Drug: Fostamatinib 150 mg
* Drug: Fostamatinib 100 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: Recent use of cyclophosphamide, mycophenolate mofetil, azathioprine, or Rituximab. Use of > 15 mg/day prednisone (or other corticosteroid equivalent).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fostamatinib 150 mg<br>Fostamatinib 150 milligram (mg) tablet twice daily by mouth, over the course of 24 weeks | Drug: Fostamatinib 150 mg<br>* Fostamatinib 150 milligram (mg) tablet twice daily by mouth, over the course of 24 weeks<br>* Other names: R788;|
| Active Comparator: Fostamatinib 100 mg<br>Fostamatinib 100 mg tablet twice daily by mouth, over the course of 24 weeks | Drug: Fostamatinib 100 mg<br>* Fostamatinib 100 mg tablet twice daily by mouth, over the course of 24 weeks<br>* Other names: R788;|
| Placebo Comparator: Placebo<br>Placebo tablet twice daily by mouth, over the course of 24 weeks | Drug: Placebo<br>* Placebo tablet twice daily by mouth, over the course of 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change of Proteinuria as Measured by Spot Urine Protein/Creatinine Ratio (sPCR) at Week 24 | 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 | Baseline to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Pre-treatment to Post-treatment in Mesangial Hypercellularity (M) on Renal Biopsies. | 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. | Baseline to Week 24 | 
| Percentage of Subjects With ≥50% Reduction in sPCR From Baseline (Visit 2) at Week 24 (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 ≥ 30% Reduction in Proteinuria From Baseline (Visit 2) at 24 Weeks (Visit 9). | Percentage of subjects with ≥ 30% reduction in proteinuria from Baseline (Visit 2) at 24 weeks (Visit 9). | Baseline to Week 24 | 
| Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Endocapillary Hypercellularity (E) on Renal Biopsies. | 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. | Baseline to Week 24 | 
| Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Segmental Sclerosis/Adhesion (S) on Renal Biopsies. | 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. | Baseline to Week 24 | 
| Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Global Glomerulosclerosis Score on Renal Biopsies. | 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. | Baseline to Week 24 | 
| Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Tubulointerstitial Scarring (T) on Renal Biopsies. | 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. | Baseline to Week 24 | 
| Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Cellular/Fibrocellular Crescent Score on Renal Biopsies. | 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. | Baseline to Week 24 | 
| Mean Change From Baseline (Visit 2) of eGFR at 12 Weeks (Visit 7). | 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 24 Weeks (Visit 9). | Mean change from Baseline (Visit 2) of eGFR at 24 weeks (Visit 9). | Baseline to Week 24 | 
| Mean Change From Baseline (Visit 2) of Proteinuria at 12 Weeks (Visit 7). | Mean change from Baseline (Visit 2) of proteinuria 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). | Percentage of subjects with sPCR <50 mg/mmol (500 mg/g) 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 12 weeks (Visit 7). | Baseline to Week 12 | 
| Shift in Haematuria (Dipstick Test) From Baseline (Visit 2) at 24 Weeks (Visit 9). | Shift in haematuria (dipstick test) from Baseline (Visit 2) at 24 weeks (Visit 9). | Baseline to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IGA Glomerulonephritis, Nephritis, IGA Type