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

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

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.
4. Mean seated blood pressure (BP) >100/60 and <140/90 in adults. Mean seated BP for children should be >90/60 and <95th percentile for age, gender, and height.
5. Patients who are on immunosuppressive medications (except for Rituximab or cyclophosphamide) at the time of screening are eligible for the study. However, the doses of the medications must be stable for at least 1 month- prior to randomization and cannot be changed during the 8-Week treatment period. Patients on Rituximab or cyclophosphamide will be eligible provided they have not been taking these medications in the prior 3 months from screening.
6. US Sites: Males or females 8 to 65 years of age able to provide written informed consent and/or assent at the time of consenting, with informed consent signed by patient or legal guardian.
7. EU Sites: Males or females 18 to 65 years of age able to provide written informed consent at the time of consenting, 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. Patients with a requirement for any of the medications indicated on the list of Excluded Medications (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. Patients positive for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) positive.
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 (HCT) <27 or hemoglobin (Hgb) <9.
12. K+ >5.5.
13. N-terminal prohormone of brain natriuretic peptide (NT-proBNP) =200 pg/mL (57.8 pmol/L) in adults.
14. Adult Patients with body mass index (BMI) >40. Pediatrics 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 Investigator as clinically significant.
16. Patients with a history of drug or alcohol abuse within the past two years.
17. Patients with a history of an allergic response to any angiotensin II antagonist or endothelin receptor antagonist.
18. Women who are pregnant or breastfeeding.
19. Female patients of child-bearing potential, defined as all women physiologically capable of becoming pregnant who are unwilling or unable to use two acceptable methods of contraception, with at least one being a barrier method, in order to avoid pregnancy for the entire study period and for 90 days post study participation. Female patients of child-bearing potential must have a negative serum pregnancy test.
20. Male patient and female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) to avoid pregnancy for the entire study period and for 90 days post study participation.
21. Patients who have participated in another investigational drug study within 28 days prior to signing the informed consent form, or who will participate in another drug study during the course of this study.
22. Prior exposure to Sparsentan, dual acting receptor antagonist (DARA), or PS433540.
23. Patients who are un

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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