Randomized, Double-Blind, Safety and Efficacy Study of RE-021 (Sparsentan) in Focal Segmental Glomerulosclerosis

NCT01613118 | Completed Phase 2 Results DMC

• 1 other identifier: RET-D-001
• Study Type: interventional
• Target: 109
• Locations: 3 countries
• Sites: 33

Brief Summary

This study will investigate whether RE-021 (Sparsentan), a selective dual-acting receptor antagonist with affinity for endothelin (A type) and angiotensin II receptors (Type 1), is safe and effective in treating patients with focal segmental glomerulosclerosis (FSGS).

Conditions

Focal Segmental Glomerulosclerosis

Keywords

Primary FSGS; Nephrotic syndrome; Steroid Resistant

Outcome Measures

Primary Outcomes (1)

• Percent Change in Urine Protein/Creatinine (Up/C)

  Primary efficacy objective is to determine the change in UP/C in FSGS patients receiving RE-021 (Sparsentan) from baseline to 8 weeks over a range of dose levels compared to treatment with irbesartan as active control.

  8 weeks

Secondary Outcomes (1)

• Percentage of Patients Achieving FSGS Partial Remission Endpoint (FPRE)

  8 weeks

Study Arms (5)

RE-021 (Sparsentan) 200 mg - Double-Blind Period

EXPERIMENTAL

RE-021 (Sparsentan) will be administered as a single oral morning dose. In this ARM the RE-021 (Sparsentan) dose will be 200mg. Patients at \</= 50kg will receive half of the RE-021 (Sparsentan) dose for the 8 week duration.

Drug: RE-021 (Sparsentan)

RE-021 (Sparsentan) 400 mg - Double-Blind Period

EXPERIMENTAL

RE-021 (Sparsentan) will be administered as a single oral morning dose. In this ARM the RE-021 (Sparsentan) dose will be 400mg. Patients at \</= 50kg will receive half of the RE-021 (Sparsentan) dose for the 8 week duration.

Drug: RE-021 (Sparsentan)

RE-021 (Sparsentan) 800 mg - Double-Blind Period

EXPERIMENTAL

RE-021 (Sparsentan) will be administered as a single oral morning dose. In this ARM the RE-021 (Sparsentan) dose will be 800mg. Patients at \</= 50kg will receive half of the RE-021 (Sparsentan) dose for the 8 week duration.

Drug: RE-021 (Sparsentan)

Irbesartan 300 mg - Double-Blind Period

ACTIVE COMPARATOR

The control will be administered irbesartan as a single oral dose of 150mg for the first week before escalating to 300mg for the remaining 7 weeks. Patients at \</= 50kg will receive 150mg irbesartan for the 8 week duration.

Drug: Irbesartan

RE-021 (Sparsentan) - Open-Label Extension Period

EXPERIMENTAL

Includes all subjects who completed the Double-Blind period and enrolled in the Open-Label Extension period of the study. All subjects who completed the Double-Blind period were evaluated for response and safety at the Week 8 visit to determine eligibility for continued treatment on their assigned doses in an Open-Label Extension period for up to 496 additional weeks. Subjects treated with irbesartan during the Double-Blind period were offered sparsentan treatment at the dose they would have received according to the Double-Blind dose cohort in which they were enrolled.

Drug: RE-021 (Sparsentan)

Interventions

RE-021 (Sparsentan) DRUG

Oral, once-daily

Also known as: Sparsentan

RE-021 (Sparsentan) - Open-Label Extension Period; RE-021 (Sparsentan) 200 mg - Double-Blind Period; RE-021 (Sparsentan) 400 mg - Double-Blind Period; RE-021 (Sparsentan) 800 mg - Double-Blind Period

Irbesartan DRUG

Oral, once-daily

Also known as: Avapro

Irbesartan 300 mg - Double-Blind Period

Eligibility Criteria

• Age: 8 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Biopsy-proven FSGS OR documentation of a genetic mutation in a podocyte protein associated with the disease.
• Urine protein/creatinine ratio (Up/C) at or above 1.0 g/g.
• Estimated glomerular filtration rate (eGFR) \>30.
• Mean seated blood pressure (BP) \>100/60 mmHg and \<145/95 in patients \>/= 18 years of age. Mean seated BP for patients \<18 years of age should be \>90/60 mmHg and \<95th percentile for age, gender, and height.
• If a patient is taking immunosuppressive medications (except for Rituximab 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.
• 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.
• 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.

You may not qualify if:

• Patients with FSGS secondary to another condition.
• 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.
• Patients who have had any organ transplant.
• Patients with a requirement for any of the medications indicated on the list of Excluded Medications, with the exception of ACE and ARBs.
• 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. Patients 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 screening.
• Patients with clinically significant cardiac conduction defects, including second or third degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation, atrial flutter, an accessory bypass tract, or any arrhythmia requiring medication.
• Patients with jaundice, hepatitis, or known hepatobiliary disease (includes asymptomatic cholelithiasis); alanine aminotransferase and/or aspartate aminotransferase \>2 times the upper limit of normal at Screening.
• Patients positive for human immunodeficiency virus (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 hepatitis C virus (HCV) infection (reactive anti-HCV antibody and/or HCV RNA). Testing at screening is only required for patients \>/= 18 years of age.
• History of malignancy other than adequately treated basal cell or squamous cell skin cancer within the past 5 years.
• Patients with hemodynamically significant valvular disease.
• Hematocrit (HCT) \<27 or hemoglobin (Hgb) \<9.
• Potassium \>5.5 mEq/L.
• NT-proBNP ≥300 pg/mL in patients \>18 years of age with eGFR 45 59.9 mL/min
• 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
• NT-proBNP ≥400 pg/mL in patients \>18 years of age with eGFR 30.0 44.9 mL/min

Sponsors & Collaborators

• Travere Therapeutics, Inc.: lead

Study Sites (33)

Balboa Nephrology Medical Group

San Diego, California, 92123, United States

Location

Los Angeles Biomedical Research Institute

Torrance, California, 90502, United States

Location

Colorado Kidney Care

Denver, Colorado, 80230, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Miami Children's Hospital

Miami, Florida, 33155, United States

Location

University of Iowa Children's Hospital

Iowa City, Iowa, 52242, United States

Location

Renal and Transplant Associates of New England, PC

Springfield, Massachusetts, 01107, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55454, United States

Location

The Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

SUNY Stony Brook Hospital

Stony Brook, New York, 11794-8111, United States

Location

UNC Kidney Center, Pediatrics

Chapel Hill, North Carolina, 27599, United States

Location

University North Carolina (UNC) Kidney Center

Chapel Hill, North Carolina, 27599, United States

Location

Akron Nephrology Associates

Akron, Ohio, 44302, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Unversity of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Northeast Clinical Research Center

Bethlehem, Pennsylvania, 18017, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Temple University School of Medicine

Philadelphia, Pennsylvania, 19140, United States

Location

University of Pennsylvania, Perelman School of Medicine

Philadelphia, Pennsylvania, 19140, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Clinical Advancement Center

San Antonio, Texas, 78215, United States

Location

Southern Utah Kidney and Hypertension Center

St. George, Utah, 84790, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Catholic Health Initiatives Franciscan

Tacoma, Washington, 98405, United States

Location

Marshfield Clinic Research Foundation

Marshfield, Wisconsin, 54449, United States

Location

General Teaching Hospital Prague

Prague, Czechia

Location

Azienda Ospedaliero Universitaria Policlinico di Bari

Bari, 70124, Italy

Location

Azienda Ospedaliero Universitaria Careggi

Florence, 50134, Italy

Location

IRCCS Istituti Clinici Maugeri

Pavia, 27100, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, 00168, Italy

Location

Related Publications (6)

• D'Agati VD, Kaskel FJ, Falk RJ. Focal segmental glomerulosclerosis. N Engl J Med. 2011 Dec 22;365(25):2398-411. doi: 10.1056/NEJMra1106556. No abstract available.

  PMID: 22187987 BACKGROUND

• Campbell KN, Gesualdo L, Murphy E, Rheault MN, Srivastava T, Tesar V, Komers R, Trachtman H. Sparsentan for Focal Segmental Glomerulosclerosis in the DUET Open-Label Extension: Long-term Efficacy and Safety. Kidney Med. 2024 Apr 26;6(6):100833. doi: 10.1016/j.xkme.2024.100833. eCollection 2024 Jun.

  PMID: 38831932 RESULT

• Trachtman H, Nelson P, Adler S, Campbell KN, Chaudhuri A, Derebail VK, Gambaro G, Gesualdo L, Gipson DS, Hogan J, Lieberman K, Marder B, Meyers KE, Mustafa E, Radhakrishnan J, Srivastava T, Stepanians M, Tesar V, Zhdanova O, Komers R; DUET Study Group. DUET: A Phase 2 Study Evaluating the Efficacy and Safety of Sparsentan in Patients with FSGS. J Am Soc Nephrol. 2018 Nov;29(11):2745-2754. doi: 10.1681/ASN.2018010091.

  PMID: 30361325 RESULT

• Liu ID, Willis NS, Craig JC, Hodson EM. Interventions for idiopathic steroid-resistant nephrotic syndrome in children. Cochrane Database Syst Rev. 2025 May 8;5(5):CD003594. doi: 10.1002/14651858.CD003594.pub7.

  PMID: 40337980 DERIVED

• Omachi K, O'Carroll C, Miner JH. PPAR delta Agonism Ameliorates Renal Fibrosis in an Alport Syndrome Mouse Model. Kidney360. 2023 Mar 1;4(3):341-348. doi: 10.34067/KID.0006662022.

  PMID: 36657027 DERIVED

• Hodson EM, Sinha A, Cooper TE. Interventions for focal segmental glomerulosclerosis in adults. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD003233. doi: 10.1002/14651858.CD003233.pub3.

  PMID: 35224732 DERIVED

MeSH Terms

Conditions

Glomerulosclerosis, Focal Segmental; Nephrotic Syndrome

Interventions

sparsentan; Irbesartan

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Nephrosis

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Spiro Compounds; Tetrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Jula Inrig, MD
• Organization: Travere Therapeutics, Inc.

Jula.Inrig@travere.com

1-445-529-6312

Study Officials

• Howard Trachtman, M.D.

  NYU School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2012
• First Posted: June 6, 2012
• Study Start: March 1, 2014
• Primary Completion: June 1, 2016
• Study Completion: March 25, 2024
• Last Updated: May 15, 2025
• Results First Posted: July 27, 2021

Record last verified: 2025-04

Locations

CZ (1); IT (4); US (28)