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

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

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

Study Overview

• Status: Completed
• Conditions: IGA Nephropathy
• Intervention / Treatment: Drug: Fostamatinib 150 mg; Drug: Fostamatinib 100 mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, A-1090
    • Medical University Vienna, Nephrology
  • Steiermark
    • Graz, Steiermark, Austria, 8036
      • Medical University of Graz
• Germany
  • Baden-Wurtemberberg
    • Heidelberg, Baden-Wurtemberberg, Germany, 69120
      • Medical University of Heidelberg
  • Bayern
    • Munich, Bayern, Germany, 80336
      • Klinikum der Universität München
  • Sachsen
    • Dresden, Sachsen, Germany, 1307
      • Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
  • Thueringen
    • Jena, Thueringen, Germany, 07747
      • Medical University of Jena
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Sha Tin
    • Hong Kong, Sha Tin, Hong Kong
      • Prince of Wales Hospital
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taoyuan, Taiwan, 333
    • School of Medicine, Chang Gung University, Chang Gung Memorial Hospital
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrookes Hospital
  • Cardiff, United Kingdom, CF14 4XN
    • Cardiff University
  • Leicester, United Kingdom, LE5 4PW
    • Leicester General Hospital
  • London, United Kingdom, W12 0NN
    • Hammersmith Hospital
  • London, United Kingdom, NW3 2PF
    • Royal Free Hospital
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Freeman Hospital
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University Medical
  • Georgia
    • Augusta, Georgia, United States, 30901
      • Nephrology Associates PC, University Hospital, Professional Center 1
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Tennessee
    • Chattanooga, Tennessee, United States, 37408
      • Southeast Renal Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Fostamatinib 150 mg; Fostamatinib 150 milligram (mg) tablet twice daily by mouth, over the course of 24 weeks	Drug: Fostamatinib 150 mg; Fostamatinib 150 milligram (mg) tablet twice daily by mouth, over the course of 24 weeks; Other Names: R935788; R788
Active Comparator: Fostamatinib 100 mg; Fostamatinib 100 mg tablet twice daily by mouth, over the course of 24 weeks	Drug: Fostamatinib 100 mg; Fostamatinib 100 mg tablet twice daily by mouth, over the course of 24 weeks; Other Names: R935788; R788
Placebo Comparator: Placebo; Placebo tablet twice daily by mouth, over the course of 24 weeks	Drug: Placebo; Placebo tablet twice daily by mouth, over the course of 24 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rigel Pharmaceuticals

Publications and helpful links

General Publications

• Yeo SC, Liew A, Barratt J. Emerging therapies in immunoglobulin A nephropathy. Nephrology (Carlton). 2015 Nov;20(11):788-800. doi: 10.1111/nep.12527.
• Prendecki M, Gulati K, Turner-Stokes T, Bhangal G, Chiappo D, Woollard K, Cook HT, Tam FW, Roufosse C, Pusey CD, McAdoo SP. Characterisation of an enhanced preclinical model of experimental MPO-ANCA autoimmune vasculitis. J Pathol. 2021 Oct;255(2):107-119. doi: 10.1002/path.5746. Epub 2021 Jul 23.
• McAdoo S, Tam FWK. Role of the Spleen Tyrosine Kinase Pathway in Driving Inflammation in IgA Nephropathy. Semin Nephrol. 2018 Sep;38(5):496-503. doi: 10.1016/j.semnephrol.2018.05.019.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): March 23, 2018
• Study Completion (Actual): November 12, 2018

Study Registration Dates

• First Submitted: April 10, 2014
• First Submitted That Met QC Criteria: April 10, 2014
• First Posted (Estimate): April 14, 2014

Study Record Updates

• Last Update Posted (Actual): June 27, 2019
• Last Update Submitted That Met QC Criteria: June 10, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: IGA Glomerulonephritis; Nephritis, IGA Type
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Kidney Diseases; Glomerulonephritis, IGA
• Other Study ID Numbers: C-935788-050; 2014-000331-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No