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Focal Segmental GlomerulosclerosisPhase 2DUETNCT01613118

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

A Phase 2 study testing RE-021 (Sparsentan) and Irbesartan in people with Focal Segmental Glomerulosclerosis, run by Travere Therapeutics, Inc. at 33 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 8 to 75 years
Conditions the study is for
Focal Segmental Glomerulosclerosis
What is being tested?
RE-021 (Sparsentan) and Irbesartan
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
109 participants
Where
33 sitesin 3 countries
Study dates
Mar 2014to 25 Mar 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 8 to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 26Show fewer
  • 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.
  • Patients >18 years of age with Estimated Glomerular Filtration Rate (eGFR) ≥60 ml mL/min who have N-terminal 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 echocardiography (ECHO) at screening should be used for exclusion:
  • 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
  • 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.
  • 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.
  • Patients who have abnormal clinical laboratory values at Screening, which are designated by the Principal Investigator as clinically significant.
  • Patients with a history of drug or alcohol abuse within the past two years.
  • Patients with a history of an allergic response to any angiotensin II antagonist or endothelin receptor antagonist.
  • Women who are pregnant or breastfeeding.
  • Women of child-bearing potential (WOCBP) who are unwilling or unable to use two reliable methods of contraception, with at least one being highly reliable (e.g. oral, implanted or injected contraceptive hormones or an intrauterine device) and one being a barrier method, in order to avoid pregnancy for the entire study period and for 90 days post study participation. WOCBP, defined as all women physiologically capable of becoming pregnant, includes any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral ovariectomy) or is not postmenopausal (defined as amenorrhea >12 consecutive months and for women on hormone replacement therapy, only with documented plasma follicle stimulating hormone level greater than 35 mIU/mL). Women using oral, implanted or injected contraceptive hormones, an intrauterine device, barrier methods (diaphragm, condoms, spermicidal) to prevent pregnancy, practicing abstinence or where the partner is sterile (e.g. vasectomy) As well as postmenopausal women who have fertilized eggs implanted are also considered WOCBP.
  • Patients who have participated in another investigational drug study within 28 days prior to screening, or who will participate in another drug study during the course of this study.
  • Prior exposure to Sparsentan, dual acting receptor antagonist (DARA), or PS433540.
  • Patients who are unable to comply with the study procedures and assessments, including the ability swallow the study drug or control capsules.

Trial locations and contacts

33 sites in 3 countries.

33 sites in 3 countries

United States28 sites

  • Akron Nephrology Associates

    Akron, Ohio, 44302

  • Northeast Clinical Research Center

    Bethlehem, Pennsylvania, 18017

  • UNC Kidney Center, Pediatrics

    Chapel Hill, North Carolina, 27599

  • University North Carolina (UNC) Kidney Center

    Chapel Hill, North Carolina, 27599

  • The Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Colorado Kidney Care

    Denver, Colorado, 80230

  • University of Iowa Children's Hospital

    Iowa City, Iowa, 52242

  • The Children's Mercy Hospital

    Kansas City, Missouri, 64108

  • Marshfield Clinic Research Foundation

    Marshfield, Wisconsin, 54449

  • University of Miami Miller School of Medicine

    Miami, Florida, 33136

  • Miami Children's Hospital

    Miami, Florida, 33155

  • University of Minnesota

    Minneapolis, Minnesota, 55454

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • NYU Langone Medical Center

    New York, New York, 10016

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

  • Columbia University Medical Center

    New York, New York, 10032

  • Unversity of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • The Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Temple University School of Medicine

    Philadelphia, Pennsylvania, 19140

  • University of Pennsylvania, Perelman School of Medicine

    Philadelphia, Pennsylvania, 19140

  • Clinical Advancement Center

    San Antonio, Texas, 78215

  • Balboa Nephrology Medical Group

    San Diego, California, 92123

  • University of Washington

    Seattle, Washington, 98195

  • Renal and Transplant Associates of New England, PC

    Springfield, Massachusetts, 01107

  • Southern Utah Kidney and Hypertension Center

    St. George, Utah, 84790

  • SUNY Stony Brook Hospital

    Stony Brook, New York, 11794-8111

  • Catholic Health Initiatives Franciscan

    Tacoma, Washington, 98405

  • Los Angeles Biomedical Research Institute

    Torrance, California, 90502

Other trials in United States

Italy4 sites

  • Azienda Ospedaliero Universitaria Policlinico di Bari

    Bari, 70124

  • Azienda Ospedaliero Universitaria Careggi

    Florence, 50134

  • IRCCS Istituti Clinici Maugeri

    Pavia, 27100

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS

    Rome, 00168

Other trials in Italy

Czechia1 site

  • General Teaching Hospital Prague

    Prague

Other trials in Czechia

About this study

Official title: 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

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).

Read the detailed description

Focal segmental glomerulosclerosis (FSGS) is a rare glomerular disorder which results in frank proteinuria and in some patients progression to end-stage kidney disease (ESKD) over 5-10 years. Proteinuria reduction is widely regarded to be beneficial and is considered the primary goal of treatment in FSGS and slowing its progressive course (D'Agati, et. al, 2011). Patients are currently treated with angiotensin receptor blockers (ARB) and angiotensin converting inhibitors (ACEI) to lower proteinuria with steroids, calcineurin inhibitors, and other immunosuppressive agents reserved for patients with severe proteinuria and in particular with nephrotic syndrome. Despite these therapies, many patients have nephrotic range proteinuria and new therapeutic agents are needed. Endothelin receptor antagonists (ERA) have been shown to lower proteinuria in clinical trials of diabetic nephropathy and have been speculated to be effective in FSGS.

Being tested
RE-021 (Sparsentan), Irbesartan
Keywords
Primary FSGS, Nephrotic syndrome, Steroid Resistant
Medical subject headings
Glomerulosclerosis, Focal Segmental, Nephrotic Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RE-021 (Sparsentan)Drug

    Also called Sparsentan

    Oral, once-daily

  • IrbesartanDrug

    Also called Avapro

    Oral, once-daily

Study groups in NCT01613118
Study groupRoleWhat they receive
RE-021 (Sparsentan) 200 mg - Double-Blind PeriodExperimentalRE-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.
Receives: Drug: RE-021 (Sparsentan)
RE-021 (Sparsentan) 400 mg - Double-Blind PeriodExperimentalRE-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.
Receives: Drug: RE-021 (Sparsentan)
RE-021 (Sparsentan) 800 mg - Double-Blind PeriodExperimentalRE-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.
Receives: Drug: RE-021 (Sparsentan)
Irbesartan 300 mg - Double-Blind PeriodActive comparatorThe 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.
Receives: Drug: Irbesartan
RE-021 (Sparsentan) - Open-Label Extension PeriodExperimentalIncludes 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.
Receives: Drug: RE-021 (Sparsentan)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 8 weeks

Secondary outcomes (1)

  1. Percentage of Patients Achieving FSGS Partial Remission Endpoint (FPRE)

    The secondary efficacy endpoint is the proportion of FSGS patients achieving FPRE (experiencing a UP/C ratio ≤1.5 g/g and >40% reduction from baseline in Up/C) at Week 8 over a range of dose levels compared to treatment with irbesartan as active control.

    Measured: 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jun 2012 (estimated)
  2. Study startMar 2014
  3. Primary completionJun 2016
  4. Study completion25 Mar 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
109 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01613118
Sponsor's protocol ID
RET-D-001
Acronym
DUET
Status last verified
Apr 2025
First submitted
4 Jun 2012
Last updated
15 May 2025
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 22187987

  • 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.

    PubMed 38831932

  • 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.

    PubMed 30361325

  • 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.

    PubMed 40337980

  • 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.

    PubMed 36657027

  • 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.

    PubMed 35224732

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RE-021 (Sparsentan) and Irbesartan in people with Focal Segmental Glomerulosclerosis, run by Travere Therapeutics, Inc. at 33 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in United States, Italy, Czechia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change in Urine Protein/Creatinine (Up/C) (time frame: 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01613118, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2025.

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