N/A

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2014-000331-16-AT
• Date of registration: 22/07/2014
• Prospective Registration: Yes
• Primary sponsor: Rigel Pharmaceuticals Inc
• Public title: N/A
• Scientific 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 - N/A
• Date of first enrolment: 25/08/2014
• Target sample size: 75
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-000331-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Hong Kong, Singapore, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: Vice President, Clinical Operations
• Affiliation: Theresa Musser

• Name: Vice President, Clinical Operations
• Affiliation: Theresa Musser

Key inclusion & exclusion criteria

Inclusion criteria:
Signed informed consent prior to any study specific screening procedures.
2. Male or female between 18 to 70 years of age.
3. Females must be either post-menopausal for at least 1 year, surgically sterile, or, if of child-bearing potential, must not be pregnant or lactating. If sexually active, must agree to use a highly effective method of birth control throughout the duration of the trial and for 30 days following the last dose.
4. A pre-study renal biopsy obtained within 180 days prior to the initial study visit (Visit 1a) will be reviewed by a member of the central panel of renal pathologists to ensure subjects meet the following histologic entry criteria:
• Consistent with IgAN
• Mesangial hypercellularity score of > 0.5 (M1) and/or presence of endocapillary hypercellularity (E1) on renal biopsy (using the Oxford Classification)
• = 50% of cortical area involved by tubular atrophy or interstitial fibrosis (T0 or T1)
• < 50% glomerular crescents
5. Treatment with an ACEi and/or an ARB for at least 90 days at a maximum approved (or tolerated) dose prior to Screening (Visit 1b). Subjects should remain on the same dose of ACEi or ARB during the treatment period (Visits 2-9).
6. Proteinuria > 1 gm/day, sPCR > 100 mg/mmol (> 884 mg/g), or Spot Albumin/Creatinine Ratio > 70 mg/mmol at diagnosis of IgAN or any time prior to screening.
7 Proteinuria > 0.50 gm/day [sPCR > 50 mg/mmol (> 442 mg/g)] at Screening (Visit 1b).
8. Blood pressure controlled to = 130/80 with angiotensin blockade with or without other anti-hypertensive agents. Subjects should be taking a maximum approved (or tolerated) dose of an ACEi or ARB before an additional anti-hypertensive agent is added. If additional anti-hypertensive therapy is required, other agents (beta blockers, calcium channel blockers, or diuretics) may be added. Patients may be reassessed if BP < 140/90, but > 130/80.
9. Otherwise in stable health as determined by the Investigator based on medical history and laboratory tests during the screening period. See Exclusion Criteria for specific exclusions.
10. In the Investigator’s opinion, has the ability to understand the nature of the study and any hazards of participation and to communicate satisfactorily with the Investigator.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1. History of or active, clinically significant, respiratory, gastrointestinal (including pancreatitis), hepatic, neurological, psychiatric, musculoskeletal, genitourinary, dermatological, or other disorder that, in the Investigator’s opinion, could affect the conduct of the study or the absorption, metabolism or excretion of the study drug.
2. Have had any major cardiovascular event within the 180 days prior to randomisation, including but not limited to: myocardial infarction, unstable angina, cerebrovascular accident, pulmonary embolism, or New York Heart Association Class III or IV heart failure.
3. Diagnosis or history suggestive of Henoch-Schonlein purpura.
4. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 (using the MDRD equation) at the time of Screening (Visit 1b).
5. A 50% decrease in eGFR from most recent pre-study clinic visit to Visit 1b.
6. An absolute neutrophil count of < 1,500/µL, Hgb < 9 g/dL, ALT or AST of > 1.5x ULN, total bilirubin > 2.0 mg/dL at Visit 1b. The Investigator may reassess these laboratory abnormalities within 30 days after Screening (Visit 1b).
7. Acute gastrointestinal symptoms (eg, nausea, vomiting, diarrhoea) at Baseline (Visit 2). The subject may be reassessed after full recovery from the acute gastrointestinal illness.
8. Active bacterial or parasitic infections, including tuberculosis.
9. Serologic results suggestive of active hepatitis B or hepatitis C (subjects may be included if confirmed hepatitis C recombinant immunoblot assay negative or hepatitis C virus RNA negative [qualitative]), or subjects with suspected human immunodeficiency virus (HIV).
10. Use within 6 months prior to pre-study renal biopsy of cyclophosphamide, mycophenolate mofetil, azathioprine, or Rituximab (or other anti-B cell therapies). Those subjects who had been treated with an anti- B cell therapy must have a normal CD19 count by Visit 1b.
11. Use of > 15 mg/day prednisone (or other corticosteroid equivalent). For those subjects taking corticosteroids for renal indication, the daily dose should not change from Baseline (Visist 2) to the end of the study drug treatment (Visit 9).
12. Prior or current use of cyclosporine or tacrolimus.
13. Have a clinically significant infection, or who are known to have an active inflammatory process (other than IgAN) at the time of Screening (Visit 1b) or Baseline (Visit 2). The subject may be reassessed after recovery from an acute infection.
14. Currently enrolled in an investigational drug or device study or have used an investigational drug or device within 30 days or 5 half-lives (whichever is longer) of Screening (Visit 1a).
15. Are unable or unwilling to follow instructions, including participation in all study assessments and visits.
16. Have a history of alcohol or substance abuse that, in the judgment of the Investigator, may impair or risk the subject’s full participation in the study.
17. Have a condition or be in a situation that the Investigator feels may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject’s participation in the study.
18. Have a known allergy and/or sensitivity to the study drug or its excipients.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

IgA nephropathy (IgAN)

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Product Name: Fostamatinib 100 mg tablet
Product Code: R935788
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Fostamatinib
CAS Number: 914295-16-2
Current Sponsor code: R788 disodium hexahydrate
Other descriptive name: FOSTAMATINIB DISODIUM
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Fostamatinib 150 mg tablet
Product Code: R935788
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Fostamatinib
CAS Number: 914295-16-2
Current Sponsor code: R788 disodium hexahydrate
Other descriptive name: FOSTAMATINIB DISODIUM
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To assess the efficacy of fostamatinib administered orally for 24 weeks to subjects with IgA nephropathy, as measured by change in renal function and histology.

Secondary Objective: To investigate the safety and tolerability of fostamatinib administered orally for 24 weeks to subjects with IgA nephropathy.

Primary end point(s): The primary efficacy endpoint is the mean change from Baseline (Visit 2) of proteinuria (as measured by spot protein-creatinine ratio sPCR) at 24 weeks (Visit 9).

Timepoint(s) of evaluation of this end point: 24 weeks

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 12 and 24 weeks

Secondary end point(s): •Percentage of subjects with = 50 % reduction in sPCR from Baseline (Visit2) at week 24 (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 mesangial hypercellularity on renal biopsies.
• Mean change from pre-treatment to post-treatment in endocapillary hypercellularity on renal biopsies.
• Mean change from pre-treatment to post-treatment in segmental sclerosis/adhesion score on renal biopsies.
• Mean change from pre-treatment to post-treatment in segmental or global glomerulosclerosis on renal biopsies.
• Mean change from pre-treatment to post-treatment in tubulointerstitial scarring on renal biopsies.
• Mean change from pre-treatment to post-treatment in cellular/fibrocellular crescent score on renal biopsies.
• 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 proteinuria at 12 weeks (Visit 7).
• Percentage of subjects with sPCR > 50 mg/mmol 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 of at 24 weeks (Visit 9).

Secondary ID(s)

NCT02112838

2014-000331-16-GB

C-935788-050

Source(s) of Monetary Support

Rigel Pharmaceuticals, Inc.