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

This study is currently recruiting participants.
Verified April 2014 by Retrophin, Inc.
Sponsor:
Information provided by (Responsible Party):
Retrophin, Inc.
ClinicalTrials.gov Identifier:
NCT01613118
First received: June 4, 2012
Last updated: April 10, 2014
Last verified: April 2014

June 4, 2012
April 10, 2014
December 2013
December 2014   (final data collection date for primary outcome measure)
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.
Change in albumin excretion rate (AER) from baseline achieved with fixed doses (100 mg, 200 mg, 400 mg, and 800 mg) of RE-021 to ARB therapy after 6 weeks of treatment. [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01613118 on ClinicalTrials.gov Archive Site
Not Provided
Determine the PK characteristics of RE-021 in patients with FSGS and proteinuria [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
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.
Not Provided
 
Randomized, Double-Blind, Safety and Efficacy Study of RE-021 (Sparsentan) in Focal Segmental Glomerulosclerosis
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

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).

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).

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Focal Segmental Glomerulosclerosis
  • Drug: RE-021 (Sparsentan)
    Oral, once-daily
    Other Name: Sparsentan
  • Drug: Irbesartan
    Oral, once-daily
    Other Name: Avapro
  • 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.

    Intervention: Drug: RE-021 (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.

    Intervention: Drug: RE-021 (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.

    Intervention: Drug: RE-021 (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.

    Intervention: Drug: Irbesartan
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
December 2015
December 2014   (final data collection date for primary outcome measure)
  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.
Both
8 Years to 65 Years
No
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
United States
 
NCT01613118
RET-D-001
Yes
Retrophin, Inc.
Retrophin, Inc.
Not Provided
Principal Investigator: Howard Trachtman, M.D. NYU School of Medicine
Retrophin, Inc.
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP