FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS) MedDRA version: 21.1 Level: PT Classification code 10067757 Term: Focal segmental glomerulosclerosis System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Name: Sparsentan
Product Code: RE-021
Pharmaceutical Form: Capsule
INN or Proposed INN: Sparsentan
CAS Number: 254740-64-2
Current Sponsor code: RE-021
Other descriptive name: SPARSENTAN
Conce
Sponsors
Travere Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Biopsy-proven primary FSGS (Primary FSGS confirmed by renal biopsy report) OR documentation of a genetic mutation in a podocyte protein associated with the disease. 2. Urine protein/creatinine ratio (Up/C) at or above 1.0 g/g. 3. Estimated glomerular filtration rate (eGFR) >30 mL/min. 4. Mean seated blood pressure (BP) >100/60 mmHg and 18 years of age. Mean seated BP for patients 90/60 mmHg and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with FSGS secondary to another condition. 2. Patients with history of type 1 diabetes mellitus, uncontrolled type 2 diabetes mellitus (HBA1c>8%), or non-fasting blood glucose >180 mg/dL at screening. 3. Patients who have had any organ transplant. 4. Pat. with a requirement for any of the medications indicated on the list of Excluded Medications, with the exception of ACE and ARBs (see Appendix A; Excluded Medications). 5. Patients with a documented history of heart failure (NYHA Class II-IV), and / or previous hospitalization for heart failure or unexplained dyspnea, orthopnea, paroxysmal nocturnal dyspnea, ascites and peripheral edema. Subjects with clinically significant cerebrovascular disease (transient ischemic attack or stroke) and/or coronary artery disease (hospitalization for myocardial infarction or unstable angina, new onset of angina with positive functional tests or coronary angiogram revealing stenosis, coronary revascularization procedure) within 6 months before the screening. 6. Patients with clinically significant cardiac conduction defects, including second or third degree atrioventricular (AV) block, left bundle branch block, sick sinus syndrome, atrial fibrillation, atrial flutter, an accessory bypass tract, or any arrhythmia requiring medication. 7. Patients with jaundice, hepatitis, or known hepatobiliary disease (includes asymptomatic cholelithiasis); alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >2 times the upper limit of normal (ULN) at Screening. 8. Pat. positive for HIV, and markers indicating acute (positivity of at least one of the following: Hepatitis B surface antigen [HBsAg], Hepatitis B "e" antigen [HBeAg], Hepatitis B virus [HBV] DNA in blood or liver, Immunoglobulin M Hepatitis B core antibody) or chronic (HBsAg and/or HBeAg and/or Hepatitis B virus [HBV] DNA positivity) HBV infection, or HCV infection (reactive anti-HCV antibody and/or HCV RNA). Testing at screening is only required for Pat. >18 years of age. 9. History of malignancy other than adequately treated basal cell or squamous cell skin cancer within the past 5 years. 10. Patients with hemodynamically significant valvular disease. 11. Hematocrit 5.5 mEq/L 13. Patients >18 years of age with eGFR =60 ml mL/min who have Nterminal prohormone of brain natriuretic peptide (NT-proBNP) =200 pg/mL (57.8 pmol/L). For patients >18 years of age with eGFR 18 years of age with eGFR 45 59.9 mL/min b. NT-proBNP = 200-299 pg/mL in patients >18 years of age with eGFR 45 59.9 mL/min, and abnormal ejection fraction (EF 18 years of age with eGFR 30.0 44.9 mL/min d. NT-proBNP = 200-399 pg/mL in patients >18 years of age with eGFR 30.0 44.9 mL/min, and abnormal ejection fraction (EF 18 years of age with body mass index (BMI) >40. Patients <18 years of age with a BMI in the 99% percentile plus 5 units. 15) Patients who have abnormal clinical laboratory values at Screening, which are designated by the Principal Investigator as clinically significant. 16) Patients with a history of drug or alcohol abuse within the past 2 years. 17) Patients with a history of an allergic response to any angiotensin II antagonist or endothel
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the change in urine protein/creatinine ratio (Up/C) after 8 weeks of treatment in FSGS patients receiving Sparsentan, a novel dual endothelin receptor and angiotensin receptor blocker, over a range of dose levels (200 mg, 400 mg, and 800 mg) compared to treatment with Irbesartan as the active control.;Secondary Objective: To evaluate * The proportion of patients that achieve the target of 30% or 50% reduction in Up/C at Week 8 * The time to and durability of achieving target improvement for Up/C by comparing the change from baseline in groups receiving fixed doses (200, 400, 800 mg) of Sparsentan versus the Irbesartan active control after 8 weeks * Changes from baseline in serum albumin in each dose group * Changes from baseline in lipid profile: total cholesterol and triglycerides, low density lipoprotein cholesterol (LDL-C),, very low density lipoprotein cholesterol, very low density lipoprotein triglyceride, low density lipoprotein cholesterol (VLDL-C) and triglycerides (VLDL-TG) and high density lipoprotein cholesterol (HDL) in each dose group * Changes from baseline in plasma renin, serum endothelin, and serum aldosterone in each dose group * Changes from baseline in quality of life for FSGS patients receiving Sparsentan versus Irbesartan active control;Primary end point(s): The primary efficacy endpoint is the change from baseline to the Week 8 visit of the natural log (ln) of the Up/C. Week 0/Randomization (baseline) and Week 8 values will be an average of two Up/C measurements at each time point. Primary Safety Objectives * To assess the safety and tolerability of Sparsentan over a range of doses by double-blind monitoring of body weight, peripheral edema, blood pressure, echocardiographic functional parameters, as well as related signs and symptoms * To compare the occurrence of adverse events in the double-blind Sparsentan treated patients versus active control Irbesartan * To compare medications required to control edema and | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate * The proportion of patients that achieve the target of 30% or 50% reduction in Up/C at Week 8 * The time to and durability of achieving target improvement for Up/C by comparing the change from baseline in groups receiving fixed doses (200 mg, 400 mg, 800 mg) of Sparsentan versus the Irbesartan control after 8 weeks * changes from baseline in serum albumin in each dose group * Changes from baseline in lipid profile: total cholesterol, very low density lipoprotein cholesterol, very low density lipoprotein triglyceride, low density lipoprotein cholesterol and high density lipoprotein cholesterol in each dose group * Changes from baseline in plasma renin, serum endothelin, and serum aldosterone in each dose group * Changes from baseline in quality of life for FSGS patients receiving Sparsentan versus Irbesartan active control;Timepoint(s) of evaluation of this end point: after the Week 8 visit and after open label phase week 312 | — |
Countries
Belgium, Czechia, Czech Republic, Italy
Contacts
Public ContactCTI EU Office
CTI Clincal Trial and Consulting Services Europe GmbH
Outcome results
None listed