Safety and Efficacy Study of Fostamatinib to Treat Immunoglobin A (IgA) Nephropathy
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| ClinicalTrials.gov Identifier: NCT02112838 |
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Recruitment Status :
Completed
First Posted : April 14, 2014
Results First Posted : June 27, 2019
Last Update Posted : June 27, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| IGA Nephropathy | Drug: Fostamatinib 150 mg Drug: Fostamatinib 100 mg Drug: Placebo | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 76 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| 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 Start Date : | October 2014 |
| Actual Primary Completion Date : | March 23, 2018 |
| Actual Study Completion Date : | November 12, 2018 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Fostamatinib 150 mg
Fostamatinib 150 milligram (mg) tablet twice daily by mouth, over the course of 24 weeks
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Drug: Fostamatinib 150 mg
Fostamatinib 150 milligram (mg) tablet twice daily by mouth, over the course of 24 weeks
Other Names:
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Active Comparator: Fostamatinib 100 mg
Fostamatinib 100 mg tablet twice daily by mouth, over the course of 24 weeks
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Drug: Fostamatinib 100 mg
Fostamatinib 100 mg tablet twice daily by mouth, over the course of 24 weeks
Other Names:
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Placebo Comparator: Placebo
Placebo tablet twice daily by mouth, over the course of 24 weeks
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Drug: Placebo
Placebo tablet twice daily by mouth, over the course of 24 weeks |
- Mean Change of Proteinuria as Measured by Spot Urine Protein/Creatinine Ratio (sPCR) at Week 24 [ Time Frame: Baseline to 24 weeks ]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
- Mean Change From Pre-treatment to Post-treatment in Mesangial Hypercellularity (M) on Renal Biopsies. [ Time Frame: Baseline to Week 24 ]
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). [ 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 ≥ 30% Reduction in Proteinuria From Baseline (Visit 2) at 24 Weeks (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).
- Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Endocapillary Hypercellularity (E) on Renal Biopsies. [ Time Frame: Baseline to Week 24 ]
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. [ Time Frame: Baseline to Week 24 ]
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. [ Time Frame: Baseline to Week 24 ]
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. [ Time Frame: Baseline to Week 24 ]
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. [ Time Frame: Baseline to Week 24 ]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). [ Time Frame: Baseline to Week 12 ]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). [ Time Frame: Baseline to Week 24 ]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). [ Time Frame: Baseline to Week 12 ]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). [ Time Frame: Baseline to Week 12 ]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). [ 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 24 Weeks (Visit 9). [ Time Frame: Baseline to Week 24 ]Shift in haematuria (dipstick test) from Baseline (Visit 2) at 24 weeks (Visit 9).
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| Ages Eligible for Study: | 18 Years to 70 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02112838
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| Study Director: | Rigel Pharmaceuticals, Inc. | Rigel Pharmaceuticals, Inc. |
Documents provided by Rigel Pharmaceuticals:
| Responsible Party: | Rigel Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT02112838 |
| Other Study ID Numbers: |
C-935788-050 2014-000331-16 ( EudraCT Number ) |
| First Posted: | April 14, 2014 Key Record Dates |
| Results First Posted: | June 27, 2019 |
| Last Update Posted: | June 27, 2019 |
| Last Verified: | June 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
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IGA Glomerulonephritis Nephritis, IGA Type |
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Kidney Diseases Glomerulonephritis, IGA Urologic Diseases Glomerulonephritis |
Nephritis Autoimmune Diseases Immune System Diseases |