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

Primary Purpose

IGA Nephropathy

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Fostamatinib 150 mg
Fostamatinib 100 mg
Placebo
Sponsored by
Rigel Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for IGA Nephropathy focused on measuring IGA Glomerulonephritis, Nephritis, IGA Type

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Stanford University Medical
  • Nephrology Associates PC, University Hospital, Professional Center 1
  • Ohio State University
  • Southeast Renal Research Institute
  • Medical University of Graz
  • Medical University Vienna, Nephrology
  • Medical University of Heidelberg
  • Klinikum der Universität München
  • Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
  • Medical University of Jena
  • Prince of Wales Hospital
  • Queen Mary Hospital
  • China Medical University Hospital
  • School of Medicine, Chang Gung University, Chang Gung Memorial Hospital
  • Addenbrookes Hospital
  • Cardiff University
  • Leicester General Hospital
  • Royal Free Hospital
  • Hammersmith Hospital
  • Freeman Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

Fostamatinib 150 mg

Fostamatinib 100 mg

Placebo

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
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)
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).
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.
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.
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.
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.
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.
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).
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).
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).
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).
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).
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).

Full Information

First Posted
April 10, 2014
Last Updated
June 10, 2019
Sponsor
Rigel Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT02112838
Brief Title
Safety and Efficacy Study of Fostamatinib to Treat Immunoglobin A (IgA) Nephropathy
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
October 2014 (undefined)
Primary Completion Date
March 23, 2018 (Actual)
Study Completion Date
November 12, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rigel Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
IGA Nephropathy
Keywords
IGA Glomerulonephritis, Nephritis, IGA Type

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
76 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fostamatinib 150 mg
Arm Type
Active Comparator
Arm Description
Fostamatinib 150 milligram (mg) tablet twice daily by mouth, over the course of 24 weeks
Arm Title
Fostamatinib 100 mg
Arm Type
Active Comparator
Arm Description
Fostamatinib 100 mg tablet twice daily by mouth, over the course of 24 weeks
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo tablet twice daily by mouth, over the course of 24 weeks
Intervention Type
Drug
Intervention Name(s)
Fostamatinib 150 mg
Other Intervention Name(s)
R935788, R788
Intervention Description
Fostamatinib 150 milligram (mg) tablet twice daily by mouth, over the course of 24 weeks
Intervention Type
Drug
Intervention Name(s)
Fostamatinib 100 mg
Other Intervention Name(s)
R935788, R788
Intervention Description
Fostamatinib 100 mg tablet twice daily by mouth, over the course of 24 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo tablet twice daily by mouth, over the course of 24 weeks
Primary Outcome Measure Information:
Title
Mean Change of Proteinuria as Measured by Spot Urine Protein/Creatinine Ratio (sPCR) at Week 24
Description
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 Outcome Measure Information:
Title
Mean Change From Pre-treatment to Post-treatment in Mesangial Hypercellularity (M) on Renal Biopsies.
Description
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
Title
Percentage of Subjects With ≥50% Reduction in sPCR From Baseline (Visit 2) at Week 24 (Visit 9).
Description
Percentage of subjects with ≥50% reduction in sPCR from Baseline (Visit 2) at Week 24 (Visit 9)
Time Frame
Baseline to Week 24
Title
Percentage of Subjects With ≥ 30% Reduction in Proteinuria From Baseline (Visit 2) at 24 Weeks (Visit 9).
Description
Percentage of subjects with ≥ 30% reduction in proteinuria from Baseline (Visit 2) at 24 weeks (Visit 9).
Time Frame
Baseline to Week 24
Title
Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Endocapillary Hypercellularity (E) on Renal Biopsies.
Description
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.
Time Frame
Baseline to Week 24
Title
Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Segmental Sclerosis/Adhesion (S) on Renal Biopsies.
Description
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
Title
Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Global Glomerulosclerosis Score on Renal Biopsies.
Description
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
Title
Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Tubulointerstitial Scarring (T) on Renal Biopsies.
Description
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
Title
Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Cellular/Fibrocellular Crescent Score on Renal Biopsies.
Description
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
Title
Mean Change From Baseline (Visit 2) of eGFR at 12 Weeks (Visit 7).
Description
Mean change from Baseline (Visit 2) of eGFR at 12 weeks (Visit 7).
Time Frame
Baseline to Week 12
Title
Mean Change From Baseline (Visit 2) of eGFR at 24 Weeks (Visit 9).
Description
Mean change from Baseline (Visit 2) of eGFR at 24 weeks (Visit 9).
Time Frame
Baseline to Week 24
Title
Mean Change From Baseline (Visit 2) of Proteinuria at 12 Weeks (Visit 7).
Description
Mean change from Baseline (Visit 2) of proteinuria at 12 weeks (Visit 7).
Time Frame
Baseline to Week 12
Title
Percentage of Subjects With sPCR <50 mg/mmol (500 mg/g) at 12 Weeks (Visit 7).
Description
Percentage of subjects with sPCR <50 mg/mmol (500 mg/g) at 12 weeks (Visit 7).
Time Frame
Baseline to Week 12
Title
Shift in Haematuria (Dipstick Test) From Baseline (Visit 2) at 12 Weeks (Visit 7).
Description
Shift in haematuria (dipstick test) from Baseline (Visit 2) at 12 weeks (Visit 7).
Time Frame
Baseline to Week 12
Title
Shift in Haematuria (Dipstick Test) From Baseline (Visit 2) at 24 Weeks (Visit 9).
Description
Shift in haematuria (dipstick test) from Baseline (Visit 2) at 24 weeks (Visit 9).
Time Frame
Baseline to Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rigel Pharmaceuticals, Inc.
Organizational Affiliation
Rigel Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Stanford University Medical
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Nephrology Associates PC, University Hospital, Professional Center 1
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30901
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Southeast Renal Research Institute
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37408
Country
United States
Facility Name
Medical University of Graz
City
Graz
State/Province
Steiermark
ZIP/Postal Code
8036
Country
Austria
Facility Name
Medical University Vienna, Nephrology
City
Vienna
ZIP/Postal Code
A-1090
Country
Austria
Facility Name
Medical University of Heidelberg
City
Heidelberg
State/Province
Baden-Wurtemberberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Klinikum der Universität München
City
Munich
State/Province
Bayern
ZIP/Postal Code
80336
Country
Germany
Facility Name
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
City
Dresden
State/Province
Sachsen
ZIP/Postal Code
1307
Country
Germany
Facility Name
Medical University of Jena
City
Jena
State/Province
Thueringen
ZIP/Postal Code
07747
Country
Germany
Facility Name
Prince of Wales Hospital
City
Hong Kong
State/Province
Sha Tin
Country
Hong Kong
Facility Name
Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
China Medical University Hospital
City
Taichung
ZIP/Postal Code
40447
Country
Taiwan
Facility Name
School of Medicine, Chang Gung University, Chang Gung Memorial Hospital
City
Taoyuan
ZIP/Postal Code
333
Country
Taiwan
Facility Name
Addenbrookes Hospital
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
Cardiff University
City
Cardiff
ZIP/Postal Code
CF14 4XN
Country
United Kingdom
Facility Name
Leicester General Hospital
City
Leicester
ZIP/Postal Code
LE5 4PW
Country
United Kingdom
Facility Name
Royal Free Hospital
City
London
ZIP/Postal Code
NW3 2PF
Country
United Kingdom
Facility Name
Hammersmith Hospital
City
London
ZIP/Postal Code
W12 0NN
Country
United Kingdom
Facility Name
Freeman Hospital
City
Newcastle upon Tyne
ZIP/Postal Code
NE7 7DN
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34124781
Citation
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.
Results Reference
derived
PubMed Identifier
30177021
Citation
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.
Results Reference
derived
PubMed Identifier
26032537
Citation
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.
Results Reference
derived

Learn more about this trial

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

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