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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Retrophin, Inc.
Sponsor:
Information provided by (Responsible Party):
Retrophin, Inc.
ClinicalTrials.gov Identifier:
NCT01613118
First received: June 4, 2012
Last updated: June 20, 2014
Last verified: June 2014
  Purpose

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).


Condition Intervention Phase
Focal Segmental Glomerulosclerosis
Drug: RE-021 (Sparsentan)
Drug: Irbesartan
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Retrophin, Inc.:

Primary Outcome Measures:
  • Evaluate change in urine protein/creatinine (Up/C). [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    Primary efficacy objective is to determine the change in Up/C in FSGS patients receiving RE-021 (Sparsentan) over a range of dose levels compared to treatment with irbesartan as active control.


Other Outcome Measures:
  • Characterize serum PK of RE-021 (Sparsentan) over the range of doses administered to FSGS patients [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    Evaluate the exposure or dose versus response relationship of primary and secondary PD/Biomarker endpoints.


Estimated Enrollment: 100
Study Start Date: December 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RE-021 (Sparsentan) 200 mg

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 the RE-021 (Sparsentan) dose for the 8 week duration.

Drug: RE-021 (Sparsentan)
Oral, once-daily
Other Name: Sparsentan
Experimental: RE-021 (Sparsentan) 400 mg

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 the RE-021 (Sparsentan) dose for the 8 week duration.

Drug: RE-021 (Sparsentan)
Oral, once-daily
Other Name: Sparsentan
Experimental: RE-021 (Sparsentan) 800 mg

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)
Oral, once-daily
Other Name: Sparsentan
Active Comparator: Irbesartan 300 mg

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
Oral, once-daily
Other Name: Avapro

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

Ages Eligible for Study:   8 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

    RATIONALE: This study will include patients with primary FSGS. In most cases, the diagnosis will be based on histopathological findings in a kidney biopsy. Detection of a podocyte mutation that is causative of FSGS will be limited to patients who have proteinuria above the threshold to qualify for the trial and who have a first order relative with biopsy-confirmed FSGS. Under these circumstances, genetic testing may be performed in lieu of a biopsy. If these patients have an abnormal genetic test result, they will be considered to have primary FSGS and will be eligible for inclusion in the study;

  2. Males or females 8 to 65 years of age with informed consent signed by patient or guardian;
  3. Mean seated BP >100/60 and <140/90 in adults. Mean seated BP for children should be <95th percentile for age, gender, and height;
  4. Urine protein/creatinine ratio at or above 1.0 g/g; and,
  5. eGFR >30.

Exclusion Criteria

  1. Patients who are on immunosuppressive medications 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 will be eligible provided they have a normal CD20 count;
  2. Use of pioglitazone within 30 days of randomization;
  3. Patients with a requirement for any of the medications indicated on the list of Excluded Medications (see Appendix A);
  4. Patients who have had a kidney transplant;
  5. Women who are pregnant and/or breastfeeding;
  6. Hospitalization for surgical procedures or anything requiring NPO status within 4 weeks of randomization and dosing;
  7. HCT <27 or Hgb <9;
  8. K+ >5.5;
  9. History of malignancy other than adequately treated basal cell or squamous cell skin cancer;
  10. NT-proBNP ≥200 pg/mL (57.8 pmol/L) in adults;
  11. Patients with a history of myocardial infarction or NYHA Class II-IV heart failure;
  12. Patients with clinically significant cardiac conduction defects, including second or third degree AV block, left bundle branch block, sick sinus syndrome, atrial fibrillation, atrial flutter, an accessory bypass tract, or any arrhythmia requiring medication;
  13. Patients with hemodynamically significant valvular disease;
  14. Patients with a history of cerebrovascular accident or transient ischemic attack;
  15. Patients with BMI >40
  16. Patients with FSGS secondary to another condition;
  17. Patients known to be HIV, HBV, or HCV positive;
  18. Patients with jaundice, hepatitis, or known hepatobiliary disease (includes asymptomatic cholelithiasis); ALT and/or AST >2 X ULN at Screening;
  19. Patients who have clinical laboratory values at Screening, which are designated by the investigator as clinically significant;
  20. Patients with history of type 1 or type 2 diabetes mellitus, or fasting blood glucose >125 mg/dL at screening (after repeating the test);
  21. Patients with a history of drug or alcohol abuse within the past two years;
  22. Patients with a history of an allergic response to any angiotensin II antagonist or endothelin receptor antagonist;
  23. Women of child bearing potential who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for the entire study period including from one month prior to randomization and for a period of at least 30 days after the last dose;
  24. 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;
  25. Prior exposure to RE-021, DARA or PS433540; or
  26. Patients who are involved in the study as research site personnel.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01613118

Contacts
Contact: Radko Komers, M.D. 1-617-500-7992 radko.komers@retrophin.com
Contact: Howard Trachtman, M.D. 646-501-2663 howard.trachtman@nyumc.org

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Contact: Daniel Feig, MD, PhD, MS    205-638-9781    dfeig@peds.uab.edu   
Contact: Stephanie Clevenger, RN, BSN, CCRC    205-638-2792    sclevenger@peds.uab.edu   
Principal Investigator: Daniel Feig, MD, PhD, MS         
United States, California
Apex Research of Riverside Recruiting
Riverside, California, United States, 92505
Contact: John Robertson, MD    951-687-6300    john.robertson@davita.com   
Contact: Lorie Estrada    951-687-6300 ext 101    lestrada@riversideapex.org   
Principal Investigator: John Robertson, MD         
Los Angeles Biomedical Research Institute Recruiting
Torrance, California, United States, 90502
Contact: Sharon Adler, MD    310-222-4104    sadler@labiomed.org   
Contact: Janine LaPage    310-991-6400    jlapage@labiomed.org   
Principal Investigator: Sharon Adler, MD         
United States, Florida
Miami Children's Hospital Recruiting
Miami, Florida, United States, 33155
Contact: Ana Parades, MD, FASN    305-662-7835    ana.paredes@mch.com   
Contact: Claudia Rodriguez Paez    305-668-5582    Claudia.RodriguezPaez@mch.com   
Principal Investigator: Ana Parades, MD, FASN         
United States, Michigan
University of Michigan School of Medicine Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Debbie Gipson, MD, MS    734-936-4210    dgipson@med.umich.edu   
Contact: Emily Herreshoff    734-232-4852    egalopin@med.umich.edu   
Principal Investigator: Debbie Gipson, MD, MS         
United States, New York
NYU Langone Medical Center Recruiting
New York, New York, United States, 10016
Contact: Howard Trachtman, M.D.    646-501-2663    howard.trachtman@nyumc.org   
Contact: Suzanne Vento, RN    646-501-2663    suzanne.vento@nyumc.org   
Principal Investigator: Howard Trachtman, M.D.         
United States, North Carolina
University North Carolina (UNC) Kidney Center Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Patrick Nachman, MD    919-966-2561 ext 260    patrick_nachman@med.unc.edu   
Contact: Anne Froment    919-966-2561 ext 247    anne_froment@med.unc.edu   
Principal Investigator: Patrick Nachman, MD         
United States, Oklahoma
Unversity of Oklahoma Health Sciences Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Pascale Lane, MD    405-271-4409    pascale-lane@ouhsc.edu   
Contact: Kathy Redmond    405-271-6306    Kathy-Redmond@ouhsc.edu   
Principal Investigator: Pascale Lane, MD         
United States, Texas
Clinical Advancement Center Recruiting
San Antonio, Texas, United States, 78215
Contact: Pablo Pergola, MD    210-223-4444    ppergola@raparesearch.com   
Contact: Alison Arellano    210-223-4444    aarellano@raparesearch.com   
Principal Investigator: Pablo Pergola, MD         
United States, Utah
Southern Utah Kidney and Hypertension Center Recruiting
St. George, Utah, United States, 84770
Contact: Carlos Mercado, MD    435-652-1135      
Contact: Margaux Casteel    435-652-1135    mrscasteel920@icloud.com   
Principal Investigator: Carlos Mercado, MD         
Sponsors and Collaborators
Retrophin, Inc.
Investigators
Principal Investigator: Howard Trachtman, M.D. NYU School of Medicine
  More Information

No publications provided

Responsible Party: Retrophin, Inc.
ClinicalTrials.gov Identifier: NCT01613118     History of Changes
Other Study ID Numbers: RET-D-001
Study First Received: June 4, 2012
Last Updated: June 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Retrophin, Inc.:
Primary FSGS
Nephrotic syndrome
Steroid Resistant

Additional relevant MeSH terms:
Glomerulosclerosis, Focal Segmental
Glomerulonephritis
Nephritis
Kidney Diseases
Urologic Diseases
Irbesartan
Angiotensin Receptor Antagonists
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Angiotensin II Type 1 Receptor Blockers
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014