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

IGA Nephropathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02112838
• Other study ID #: C-935788-050
• Secondary ID: 2014-000331-16
• Status: Completed
• Phase: Phase 2
• Start date: October 2014
• Est. completion date: November 12, 2018

Study information

• Verified date: June 2019
• Source: Rigel Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 76
• Est. completion date: November 12, 2018
• Est. primary completion date: March 23, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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).

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• IGA Nephropathy
• Kidney Diseases

Intervention

Drug:
• Fostamatinib 150 mg
Fostamatinib 150 milligram (mg) tablet twice daily by mouth, over the course of 24 weeks
• Fostamatinib 100 mg
Fostamatinib 100 mg tablet twice daily by mouth, over the course of 24 weeks
• Placebo
Placebo tablet twice daily by mouth, over the course of 24 weeks

Locations

Country	Name	City	State
Austria	Medical University of Graz	Graz	Steiermark
Austria	Medical University Vienna, Nephrology	Vienna
Germany	Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden	Dresden	Sachsen
Germany	Medical University of Heidelberg	Heidelberg	Baden-Wurtemberberg
Germany	Medical University of Jena	Jena	Thueringen
Germany	Klinikum der Universität München	Munich	Bayern
Hong Kong	Prince of Wales Hospital	Hong Kong	Sha Tin
Hong Kong	Queen Mary Hospital	Hong Kong
Taiwan	China Medical University Hospital	Taichung
Taiwan	School of Medicine, Chang Gung University, Chang Gung Memorial Hospital	Taoyuan
United Kingdom	Addenbrookes Hospital	Cambridge
United Kingdom	Cardiff University	Cardiff
United Kingdom	Leicester General Hospital	Leicester
United Kingdom	Hammersmith Hospital	London
United Kingdom	Royal Free Hospital	London
United Kingdom	Freeman Hospital	Newcastle upon Tyne
United States	Nephrology Associates PC, University Hospital, Professional Center 1	Augusta	Georgia
United States	Southeast Renal Research Institute	Chattanooga	Tennessee
United States	Ohio State University	Columbus	Ohio
United States	Stanford University Medical	Palo Alto	California

Sponsors (1)

Lead Sponsor	Collaborator
Rigel Pharmaceuticals

Countries where clinical trial is conducted

United States,  Austria,  Germany,  Hong Kong,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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