Clinical trial NCT02112838: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: IGA Nephropathy
Keywords: IGA Glomerulonephritis
Nephritis, IGA Type
Lead sponsor: Rigel Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2014-04-14
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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).

Primary outcomes:
measure: Mean Change of Proteinuria as Measured by Spot Urine Protein/Creatinine Ratio (sPCR) at Week 24
timeFrame: Baseline to 24 weeks
Secondary outcomes:
measure: Mean Change From Pre-treatment to Post-treatment in Mesangial Hypercellularity (M) on Renal Biopsies.
timeFrame: Baseline to Week 24
measure: Percentage of Subjects With ≥50% Reduction in sPCR From Baseline (Visit 2) at Week 24 (Visit 9).
timeFrame: Baseline to Week 24
measure: Percentage of Subjects With ≥ 30% Reduction in Proteinuria From Baseline (Visit 2) at 24 Weeks (Visit 9).
timeFrame: Baseline to Week 24
measure: Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Endocapillary Hypercellularity (E) on Renal Biopsies.
timeFrame: Baseline to Week 24
measure: Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Segmental Sclerosis/Adhesion (S) on Renal Biopsies.
timeFrame: Baseline to Week 24
measure: Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Global Glomerulosclerosis Score on Renal Biopsies.
timeFrame: Baseline to Week 24
measure: Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Tubulointerstitial Scarring (T) on Renal Biopsies.
timeFrame: Baseline to Week 24
measure: Mean Change From Pre-treatment to Post-treatment in Percentage of Glomeruli With Cellular/Fibrocellular Crescent Score on Renal Biopsies.
timeFrame: Baseline to Week 24
measure: Mean Change From Baseline (Visit 2) of eGFR at 12 Weeks (Visit 7).
timeFrame: Baseline to Week 12
measure: Mean Change From Baseline (Visit 2) of eGFR at 24 Weeks (Visit 9).
timeFrame: Baseline to Week 24
measure: Mean Change From Baseline (Visit 2) of Proteinuria at 12 Weeks (Visit 7).
timeFrame: Baseline to Week 12
measure: Percentage of Subjects With sPCR <50 mg/mmol (500 mg/g) at 12 Weeks (Visit 7).
timeFrame: Baseline to Week 12
measure: Shift in Haematuria (Dipstick Test) From Baseline (Visit 2) at 12 Weeks (Visit 7).
timeFrame: Baseline to Week 12
measure: Shift in Haematuria (Dipstick Test) From Baseline (Visit 2) at 24 Weeks (Visit 9).
timeFrame: Baseline to Week 24
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University Medical
state: California
city: Augusta
country: United States
facility: Nephrology Associates PC, University Hospital, Professional Center 1
state: Georgia
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Chattanooga
country: United States
facility: Southeast Renal Research Institute
state: Tennessee
city: Graz
country: Austria
facility: Medical University of Graz
state: Steiermark
city: Vienna
country: Austria
facility: Medical University Vienna, Nephrology
city: Heidelberg
country: Germany
facility: Medical University of Heidelberg
state: Baden-Wurtemberberg
city: Munich
country: Germany
facility: Klinikum der Universität München
state: Bayern
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
state: Sachsen
city: Jena
country: Germany
facility: Medical University of Jena
state: Thueringen
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
state: Sha Tin
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taoyuan
country: Taiwan
facility: School of Medicine, Chang Gung University, Chang Gung Memorial Hospital
city: Cambridge
country: United Kingdom
facility: Addenbrookes Hospital
city: Cardiff
country: United Kingdom
facility: Cardiff University
city: Leicester
country: United Kingdom
facility: Leicester General Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Freeman Hospital
Study officials:
affiliation: Rigel Pharmaceuticals,Inc.
name: Rigel Pharmaceuticals, Inc.
role: STUDY_DIRECTOR
References:
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.
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.
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.