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

Rigel Pharmaceuticals76 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

IGA Nephropathy

Interventions

Fostamatinib 150 mgDRUG

Fostamatinib 150 milligram (mg) tablet twice daily by mouth, over the course of 24 weeks

Fostamatinib 100 mgDRUG

Fostamatinib 100 mg tablet twice daily by mouth, over the course of 24 weeks

PlaceboDRUG

Placebo tablet twice daily by mouth, over the course of 24 weeks

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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).

Locations (20)

Stanford University Medical

Palo Alto, California, United States

Nephrology Associates PC, University Hospital, Professional Center 1

Outcomes

Primary Outcomes

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

Time frame: Baseline to 24 weeks

Secondary Outcomes

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.

Time frame: 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)

Time frame: 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).

Time frame: 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.

Data from ClinicalTrials.gov

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Augusta, Georgia, United States

Ohio State University

Columbus, Ohio, United States

Southeast Renal Research Institute

Chattanooga, Tennessee, United States

Medical University of Graz

Graz, Styria, Austria

Medical University Vienna, Nephrology

Vienna, Austria

Medical University of Heidelberg

Heidelberg, Baden-Wurtemberberg, Germany

Klinikum der Universität München

Munich, Bavaria, Germany

Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden

Dresden, Saxony, Germany

Medical University of Jena

Jena, Thuringia, Germany

...and 10 more locations

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: 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).

Time frame: Baseline to Week 24