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

Information source: Retrophin, Inc.
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Focal Segmental Glomerulosclerosis

Intervention: RE-021 (Sparsentan) (Drug); Irbesartan (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Retrophin, Inc.

Official(s) and/or principal investigator(s):
Howard Trachtman, M.D., Principal Investigator, Affiliation: NYU School of Medicine

Overall contact:
Radko Komers, M.D., Phone: 1-617-500-7919, Email: radko.komers@retrophin.com

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).

Clinical Details

Official title: Efficacy and Safety of 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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Evaluate change in urine protein/creatinine (Up/C).

Detailed description: Focal segmental glomerulosclerosis (FSGS) is a rare glomerular disorder which results in frank proteinuria and 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 steroids, calcineurin inhibitors, angiotensin receptor blockers (ARB) and angiotensin converting inhibitors (ACE) to lower proteinuria (Cameron, 2003). Despite these therapies, many patients have nephrotic range proteinuria and new therapeutic agents are needed (Kiffel, et. al, 2011). Endothelin receptor antagonists (ERA) have been shown to lower proteinuria in clinical trials of diabetic nephropathy (Kohan, et. al, 2011) (Mann, et. al 2010) and have been speculated to be effective in FSGS (Barton, 2010).

Eligibility

Minimum age: 8 Years. Maximum age: 75 Years. Gender(s): Both.

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. 4. 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. 5. 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. 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. 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, with the exception of ACE and ARBs. 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. 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. 6. 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. 7. 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. 8. 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. 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. Potassium >5. 5 mEq/L. 13. 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: 1. NT-proBNP ≥300 pg/mL in patients >18 years of age with eGFR 45 59. 9 mL/min 2. 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 3. NT-proBNP ≥400 pg/mL in patients >18 years of age with eGFR 30. 0 44. 9 mL/min 4. 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 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. 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. 20. Male patients and female spouse/partners who are of child-bearing potential must use two reliable methods of contraception, with at least one being highly reliable (e. g. including oral, implanted or injected contraceptive hormones or an intrauterine device) and one being a barrier method, e. g. condom, 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 screening, 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 unable to comply with the study procedures and assessments, including the ability swallow the study drug or control capsules.

Locations and Contacts

Radko Komers, M.D., Phone: 1-617-500-7919, Email: radko.komers@retrophin.com

UZ Leuven, Leuven, Belgium; Recruiting
Ben Sprangers, MD, Phone: ++3216344580, Email: ben.sprangers@uzleuven.be
Ben Sprangers, MD, PhD, Principal Investigator

Fondazione Salvatore Maugeri IRCCS, Pavia, Italy; Recruiting
Ciro Esposito, Prof, Phone: +390 382592972, Email: ciro.esposito@fsm.it
Paola Tilocca, Phone: +39 0382 592 680, Email: paola.tilocca@fsm.it
Ciro Esposito, Prof, Principal Investigator

Complesso Integrato Columbus, Rome, Italy; Recruiting
Giovanni Gambaro, MD, Phone: +29063503434, Email: giovanni.gambaro@rm.unicatt.it
Giovanni Gambaro, MD, Principal Investigator

University of Alabama at Birmingham, Birmingham, Alabama 35233, United States; Recruiting
Daniel Feig, MD, PhD, MS, Phone: 205-638-9781, Email: dfeig@peds.uab.edu
Stephanie Clevenger, RN, BSN, CCRC, Phone: 205-638-2792, Email: sclevenger@peds.uab.edu
Daniel Feig, MD, PhD, MS, Principal Investigator

AKDHC Medical Research Services, Phoenix, Arizona 85032, United States; Recruiting
Esmat Mustafa, MD, Phone: 602-351-3022, Email: emustafa@akdhc.com
Erica Mustafa, Phone: 602-351-3041, Email: ediaz@akdhc.com
Esmat Mustafa, MD, Principal Investigator

Apex Research of Riverside, Riverside, California 92505, United States; Recruiting
John Robertson, MD, Phone: 951-687-6300, Email: john.robertson@davita.com
Lorie Estrada, Phone: 951-687-6300, Ext: 101, Email: lestrada@riversideapex.org
John Robertson, MD, Principal Investigator

Los Angeles Biomedical Research Institute, Torrance, California 90502, United States; Recruiting
Sharon Adler, MD, Phone: 310-222-4104, Email: sadler@labiomed.org
Janine LaPage, Phone: 310-991-6400, Email: jlapage@labiomed.org
Sharon Adler, MD, Principal Investigator

Denver Nephrology, Denver, Colorado 80218, United States; Recruiting
Brad Marder, MD, Phone: 303-861-4845, Email: bmarder@denverneph.net
Patricia Noel, Phone: 303-869-2155, Email: pnoel@denverneph.net
Brad Marder, MD, Principal Investigator

Miami Children's Hospital, Miami, Florida 33155, United States; Recruiting
Ana Parades, MD, FASN, Phone: 305-662-7835, Email: ana.paredes@mch.com
Claudia Rodriguez Paez, Phone: 305-668-5582, Email: Claudia.RodriguezPaez@mch.com
Ana Parades, MD, FASN, Principal Investigator

University of Miami Miller School of Medicine, Miami, Florida 33136, United States; Recruiting
Alessia Fornoni, MD, Phone: 305-243-6558, Email: AFORNONI@MED.MIAMI.EDU
Alessia Fornoni, MD, Principal Investigator

Northshore University Health System, Evanston, Illinois 60201, United States; Recruiting
Neenoo Khosla, MD, Phone: 847-570-2512, Email: nkhosla@northshore.org
Shonny Fettman, Phone: 847-570-2512, Email: sfettman@northshore.org
Neenoo Khosla, MD, Principal Investigator

University of Iowa Children's Hospital, Iowa City, Iowa 52242, United States; Recruiting
Carla Nester, MD, Phone: 319-353-7335, Email: carla-nester@uiowa.edu
Doug Russo, Phone: 319-467-5109, Email: douglas-russo@uiowa.edu
Carla Nester, MD, Principal Investigator

Johns Hopkins, Baltimore, Maryland 21287, United States; Recruiting
Alicia Neu, MD, Phone: 410-955-2467, Email: aneu1@jhmi.edu
Sara Boynton, Phone: 443-287-9051, Email: sboynto3@jhmi.edu
Alicia Neu, MD, Principal Investigator

Western New England Renal & Transplant Associates, Springfield, Massachusetts 01107, United States; Recruiting
Michael Germain, MD, Phone: 413-733-9666, Email: michael.germain@bhs.org
Lili Quiterio, Phone: 413-733-9666, Email: l.quiterio2002@gmail.com
Michael Germain, MD, Principal Investigator

University of Michigan School of Medicine, Ann Arbor, Michigan 48109, United States; Recruiting
Debbie Gipson, MD, MS, Phone: 734-936-4210, Email: dgipson@med.umich.edu
Emily Herreshoff, Phone: 734-232-4852, Email: egalopin@med.umich.edu
Debbie Gipson, MD, MS, Principal Investigator

The Children's Mercy Hospital, Kansas City, Missouri 64108, United States; Recruiting
Tarak Srivastava, MD, Phone: 816-234-3010, Email: tsrivastava@cmh.edu
Connie Hanney, Phone: 816-701-1395, Email: cjhaney@cmh.edu
Tarak Srivastava, MD, Principal Investigator

Hackensack University Medical Center, Hackensack, New Jersey 07601, United States; Recruiting
Kenneth Lieberman, MD, Phone: 551-996-8228, Email: klieberman@hackensackumc.org
Mary Ellen Riordan, Phone: 551-996-8126, Email: mriordan@hackensackumc.org
Kenneth Lieberman, MD, Principal Investigator

Cohen Children's Medical Center of NY, New Hyde Park, New York 11040, United States; Recruiting
Nataliya Chorny, MD, Phone: 718-470-3491, Email: NCHORNY@NSHS.EDU
Rachel Frank, Phone: 718-470-3493, Email: rfrank@nshs.edu
Nataliya Chorny, MD, Principal Investigator

Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States; Recruiting
Kirk Campbell, MD, Phone: 212-241-6271, Email: kirk.campbell@mssm.edu
Shanika Gregory, Phone: 212-659-8375, Email: shanika.gregory@mssm.edu
Kirk Campbell, MD, Principal Investigator

NYU Langone Medical Center, New York, New York 10016, United States; Recruiting
Howard Trachtman, M.D., Phone: 646-501-2663, Email: howard.trachtman@nyumc.org
Suzanne Vento, RN, Phone: 646-501-2663, Email: suzanne.vento@nyumc.org
Howard Trachtman, M.D., Principal Investigator

SUNY Stony Brook Hospital, Stony Brook, New York 11794-8111, United States; Recruiting
Robert Woroniecki, MD, Email: robert.woroniecki@stonybrookmedicine.edu
Kathryn Fassnacht, Phone: 631-444-7884, Email: kathryn.fassnacht@stonybrookmedicine.edu
Robert Woroniecki, MD, Principal Investigator

University North Carolina (UNC) Kidney Center, Chapel Hill, North Carolina 27599, United States; Recruiting
Vimal Derebail, MD, MPH, Phone: 919-966-2561, Ext: 225, Email: vimal_derebail@med.unc.edu
Anne Froment, Phone: 919-966-2561, Ext: 247, Email: anne_froment@med.unc.edu
Vimal Derebail, MD, Principal Investigator

Metrolina Nephrology Associates, Charlotte, North Carolina 28204, United States; Recruiting
Matthew Elliott, MD, Phone: 704-731-6830, Email: MELLIOTT@METROLINANEPHROLOGY.COM
Debra Wright, Phone: 704-731-6830, Email: dwright@metrolinanephrology.com
Matthew Elliott, MD, Principal Investigator

The Cleveland Clinic Foundation, Cleveland, Ohio 44195, United States; Recruiting
Katherine Dell, MD, Phone: 216-444-6113, Email: dellk@ccf.org
Donna Lach, Phone: 216-444-5034, Email: lachd@ccf.org
Katherine Dell, MD, Principal Investigator

Nationwide Children's Hospital, Columbus, Ohio 43205, United States; Recruiting
John Mahan, MD, Phone: 614-722-4360, Email: john.mahan@nationwidechildrens.org
Marcia Dyas, Phone: 614-722-4360, Email: marcia.dyas@nationwidechildrens.org
John Mahan, MD, Principal Investigator

Unversity of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, United States; Recruiting
Pascale Lane, MD, Phone: 405-271-4409, Email: pascale-lane@ouhsc.edu
Kathy Redmond, Phone: 405-271-6306, Email: Kathy-Redmond@ouhsc.edu
Pascale Lane, MD, Principal Investigator

Northeast Clinical Research Center, Bethlehem, Pennsylvania 18017, United States; Recruiting
Nelson Kopyt, MD, Phone: 610-433-4100, Email: nkopyt@gmail.com
Jenna Camacho, Phone: 610-433-4100, Ext: 490, Email: jenna.camacho@necresearch.org
Nelson Kopyt, MD, Principal Investigator

Temple University School of Medicine, Philadelphia, Pennsylvania 19140, United States; Recruiting
Duncan Johnstone, MD, Phone: 215-707-0744, Email: duncan.johnstone@tuhs.temple.edu
Zoe Pfeffer, Phone: 215-707-4712, Email: zoe.pfeffer@tuhs.temple.edu
Duncan Johnstone, MD, Principal Investigator

The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States; Recruiting
Kevin Meyers, MD, Phone: 215-590-2449, Email: MEYERSK@EMAIL.CHOP.EDU
Jessica Lalli, Phone: 570-506-4896, Email: lallij@email.chop.edu
Kevin Meyers, MD, Principal Investigator

University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States; Recruiting
Jonathan Hogan, MD, Email: jonathan.hogan2@uphs.upenn.edu
Krishna Kallem, Phone: 484-358-0315, Email: krishna.kallem@uphs.upenn.edu
Jonathan Hogan, MD, Principal Investigator

Le Bonheur Children's Hospital, Memphis, Tennessee 38103, United States; Recruiting
John Bissler, MD, Phone: 901-287-5336, Email: jbissler@uthsc.edu
Mary Edna Parish, Phone: 901-287-5527, Email: maryedna.parish@lebonheur.org
John Bissler, MD, Principal Investigator

Clinical Advancement Center, San Antonio, Texas 78215, United States; Recruiting
Pablo Pergola, MD, Phone: 210-223-4444, Email: ppergola@raparesearch.com
Alison Arellano, Phone: 210-223-4444, Email: aarellano@raparesearch.com
Pablo Pergola, MD, Principal Investigator

Southern Utah Kidney and Hypertension Center, St. George, Utah 84770, United States; Recruiting
Carlos Mercado, MD, Phone: 435-652-1135
Margaux Casteel, Phone: 435-652-1135, Email: mrscasteel920@icloud.com
Carlos Mercado, MD, Principal Investigator

Seattle Children's Hospital, Seattle, Washington 98105, United States; Recruiting
Joseph Flynn, MD, Phone: 206-987-2524, Email: joseph.flynn@seattlechildrens.org
Megan Kelton-Rehkopf, Phone: 206-884-1422, Email: megan.keltonr@seattlechildrens.org
Joseph Flynn, MD, Principal Investigator

University of Washington, Seattle, Washington 98195, United States; Recruiting
Peter Nelson, MD, Phone: 206-616-0103, Email: PNELSON@NEPHROLOGY.WASHINGTON.EDU
Karina Klepach, Phone: 206-543-8157, Email: kkhome@nephrology.washington.edu
Peter Nelson, MD, Principal Investigator

Additional Information

Starting date: December 2013
Last updated: July 17, 2015

Page last updated: August 20, 2015

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