PROTOCOL RET-D-001: EFFICACY AND SAFETY OF SPARSENTAN (RE-021), A DUAL ENDOTHELIN RECEPTOR AND ANGIOTENSIN RECEPTOR BLOCKER, IN PATIENTS WITH FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS): A RANDOMIZED, DOUBLE-BLIND, ACTIVE-CONTROL, DOSE-ESCALATION STUDY

Phase 1

• Conditions: FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS); MedDRA version: 21.1Level: PTClassification code 10067757Term: Focal segmental glomerulosclerosisSystem Organ Class: 10038359 - Renal and urinary disorders; Therapeutic area: Diseases [C] - Symptoms and general pathology [C23]

• Registration Number: EUCTR2014-002358-38-CZ
• Lead Sponsor: Travere Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-10-14
• Last Update Posted: 6 May 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 100

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 <145/95 mmHg in patients >18 years of age. Mean seated BP for patients <18 should be >90/60 mmHg and <95th percentile for age, gender, and height.
5. If a patient is taking immunosuppressive medications (except for Rituximamb or cyclophosphamide), the dose and/or levels must be stable for 1 month prior to randomization and the Investigator should not have plans to alter the regimen during the first 8 weeks of treatment, except to stabilize levels. Patients on Rituximab or cyclophosphamide will be eligible provided they have not been taking these medications for 3 months prior to randomization.
6. US Sites: Males or females 8 to 75 years of age willing and able to provide written informed consent and/or assent, with informed consent signed by patient or parent/legal guardian.
7. EU Sites: Males or females 18 to 75 years of age willing and able to provide written informed consent, with informed consent, signed by patient or legal guardian.
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 100
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 <27 g/dL or hemoglobin <9 %.
12. Potassium >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 <60 mL/min, the following parameters requiring ECHO at screening should be used for exclusion:
a. NT-proBNP =300 pg/mL in patients >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 <55) and/or diastolic dysfunction on ECHO
c. NT-proBNP =400 pg/mL in patients >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 <55) and/or diastolic dysfunction on ECHO.
14) Patients >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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified