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A Study of the Effect and Safety of Sparsentan in the Treatment of Patients With IgA Nephropathy (PROTECT)

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ClinicalTrials.gov Identifier: NCT03762850
Recruitment Status : Active, not recruiting
First Posted : December 4, 2018
Last Update Posted : June 23, 2021
Sponsor:
Information provided by (Responsible Party):
Travere Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE November 27, 2018
First Posted Date  ICMJE December 4, 2018
Last Update Posted Date June 23, 2021
Actual Study Start Date  ICMJE December 20, 2018
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 17, 2021)
Urine protein/creatinine ratio (UP/C) at Week 36 [ Time Frame: After the last patient randomized has undergone the Week 36 visit ]
The primary efficacy endpoint is the change from baseline (Day 1) in the UP/C based on a 24-hour urine sample at Week 36.
Original Primary Outcome Measures  ICMJE
 (submitted: November 30, 2018)
Urine protein/creatinine ratio (UP/C) at Week 36 [ Time Frame: After the last patient randomized has undergone the Week 36 visit ]
The primary efficacy endpoint is the change from baseline in the urine protein/creatinine ratio (UP/C), based on a 24-hour urine sample, at Week 36.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2021)
  • eGFR over a 52-week period [ Time Frame: Week 58 postrandomization ]
    The rate of change in estimated glomerular filtration rate (eGFR) over a 52-week period following the initial acute effect of randomized therapy (the initial acute effect of randomized therapy is defined as the first 6 weeks of randomized treatment with study medication; thus, the analysis is from 6 weeks postrandomization to 58 weeks postrandomization eGFR chronic slope at 1 year.)
  • eGFR over a 104-week period [ Time Frame: Week 110 postrandomization ]
    The rate of change in estimated glomerular filtration rate (eGFR) over a 104-week period following initial acute effect of randomized therapy (the initial acute effect of randomized therapy is defined as the first 6 weeks of randomized treatment with study medication; thus, the analysis is from 6 weeks postrandomization to 110 weeks postrandomization eGFR chronic slope at 2 years.)
  • eGFR over a 110-week period [ Time Frame: Week 110 postrandomization ]
    The rate of change in eGFR over a 110-week (approximately 2 years) period following the initiation of randomized therapy (thus, the analysis is from Day 1 to 110 weeks postrandomization eGFR total slope at 2 years).
Original Secondary Outcome Measures  ICMJE
 (submitted: November 30, 2018)
  • Overall eGFR change from baseline [ Time Frame: Week 114 post-randomization ]
    Change in eGFR from baseline (Week 0) to 4 weeks post-cessation of randomized treatment (Week 114).
  • eGFR over a 52-week period [ Time Frame: Week 58 post-randomization ]
    The rate of change in estimated glomerular filtration rate (eGFR) over a 52-week period following the initial acute effect of randomized therapy (the initial acute effect of randomized therapy is defined as the first 6 weeks of randomized treatment with study medication; thus, the analysis is from 6 weeks post-randomization to 58 weeks post-randomization).
  • eGFR over a 104-week period [ Time Frame: Week 110 post-randomization ]
    The rate of change in estimated glomerular filtration rate (eGFR) over a 104-week period following initial acute effect of randomized therapy (the initial acute effect of randomized therapy is defined as the first 6 weeks of randomized treatment with study medication; thus, the analysis is from 6 weeks post-randomization to 110 weeks post-randomization).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of the Effect and Safety of Sparsentan in the Treatment of Patients With IgA Nephropathy
Official Title  ICMJE A Randomized, Multicenter, Double-blind, Parallel-group, Active-control Study of the Efficacy and Safety of Sparsentan for the Treatment of Immunoglobulin A Nephropathy
Brief Summary To determine the long-term (approximately 2 years) nephroprotective potential of treatment with sparsentan as compared to an angiotensin receptor blocker in patients with immunoglobulin A nephropathy (IgAN).
Detailed Description

This is a 114-week,randomized, multicenter, double-blind, parallel-group, active-control study with an open-label extension period of up to 156 weeks, for a total duration of up to 270 weeks in patients with IgAN who have persistent overt proteinuria and remain at high risk of disease progression despite being on a stable dose (or doses) of an angiotensin-converting enzyme inhibitor (ACEI) and/or angiotensin receptor blocker (ARB) that is (are) a maximum tolerated dose that is at least one half of the maximum labeled dose (MLD) (according to approved labeling. Approximately 380 patients aged ≥18 years will be enrolled in the study globally. The investigational drug (sparsentan) is a dual acting angiotensin receptor blocker and endothelin receptor antagonist. The active control is irbesartan.

The purpose of the study is to evaluate the potential benefit of sparsentan on kidney function by analyzing change in proteinuria (protein in urine) and estimated glomerular filtration rate (eGFR) as compared to current standard treatment.

Patients enrolled in the PROTECT study (Protocol 021IGAN17001) will be those at high risk of progressing to renal failure. They will be randomly assigned in a 1:1 ratio to either sparsentan or irbesartan, as the active control (current standard treatment) at the Day 1 (Randomization) visit. Study medication (sparsentan and irbesartan) will be administered as a single oral morning dose.

The primary analysis is change in proteinuria (urine protein/creatinine ratio) from baseline at Week 36 in sparsentan-treated patients as compared to irbesartan-treated patients.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Immunoglobulin A Nephropathy
Intervention  ICMJE
  • Drug: sparsentan
    Target dose of 400 mg daily
    Other Name: RE-021
  • Drug: irbesartan
    Target dose of 300 mg daily
    Other Name: Irbesartan Tablets USP
Study Arms  ICMJE
  • Experimental: sparsentan
    Sparsentan will be administered daily as a 200-mg oral tablet, over-encapsulated (blinded) size 00 capsule for the first 2 weeks of the study following randomization. For patients who tolerate the initial dose of 200 mg after 2 weeks will increase their dose to 400 mg and continue treatment to Week 110.
    Intervention: Drug: sparsentan
  • Active Comparator: irbesartan
    Irbesartan will be administered daily as a 150-mg oral tablet, over-encapsulated (blinded) size 00 capsule for the first 2 weeks of the study following randomization. For patients who tolerate the initial dose of 150 mg after 2 weeks will increase their dose to 300 mg and continue treatment to Week 110.
    Intervention: Drug: irbesartan
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: October 29, 2020)
380
Original Estimated Enrollment  ICMJE
 (submitted: November 30, 2018)
280
Estimated Study Completion Date  ICMJE April 2023
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria for the Double-Blind Period:

  • Age 18 years or older at screening
  • Biopsy-proven primary IgAN
  • Proteinuria of ≥1 g/day at screening
  • eGFR ≥30 mL/min/1.73 m2 at screening
  • Currently on stable dose of ACEI and/or ARB therapy, for at least 12 weeks prior to screening (maximum tolerated dose and at least one-half of the maximum labeled dose)
  • Systolic BP ≤150 mmHg and diastolic BP ≤100 mmHg at screening
  • Willing to undergo change in ACEI and/or ARB and anti-hypertensive medications
  • Agree to contraception

Key Exclusion Criteria for the Double-Blind Period:

  • IgAN secondary to another condition
  • Presence of cellular glomerular crescents in >25% of glomeruli on renal biopsy (if biopsy available within 6 months of screening)
  • Chronic kidney disease (CKD) in addition to IgAN
  • History of organ transplantation, with exception of corneal transplants
  • Require any prohibited medications
  • Treatment of systemic immunosuppressive medications (including corticosteroids) for >2 weeks within 3 months of screening
  • History of heart failure or previous hospitalization for heart failure or unexplained dyspnea, orthopnea, paroxysmal nocturnal dyspnea, ascites, and/or peripheral edema
  • Clinically significant cerebrovascular disease or coronary artery disease within 6 months of screening
  • Jaundice, hepatitis, or known hepatobiliary disease or elevations of transaminases (ALT/AST) >2 times upper limit of normal at screening
  • History of malignancy other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma within the past 2 years
  • Hematocrit value <27% (0.27 V/V) or hemoglobin value <9 g/dL (90 g/L) at Screening
  • Potassium >5.5 mEq/L (5.5 mmol/L) at Screening
  • History of alcohol of illicit drug use disorder
  • History of serious side effect or allergic response to any angiotensin II antagonist or endothelin receptor antagonist, including sparsentan or irbesartan, or has a hypersensitivity to any of the excipients in the study medications
  • For female: Pregnancy, or planning to become pregnant during the course of the study, or breastfeeding
  • Participation in a study of another investigational product within 28 days of screening

Key Inclusion Criteria for the Open-Label Extension Period based on assessments at the Week 110 visit:

  • Completed participation in the double-blind period, including the Week 114 visit
  • Did not permanently discontinue study medication during the double-blind period
  • Agree to contraception

Key Exclusion Criteria for the Open-Label Extension Period based on assessments at the Week 110 and Week 114 visits:

  • Progression to end-stage renal disease (ESRD) requiring renal replacement therapy (RRT)
  • Development of any criteria for discontinuation of study medication or discontinuation from the study, between Week 110 and Week 114
  • Patient was unable to initiate, or developed contraindications to, treatment with RAAS inhibitors between Week 110 and Week 114
  • eGFR ≤20 mL/min/1.73 m2 at Week 110
  • Female patient is pregnant or breastfeeding
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Croatia,   Czechia,   Estonia,   France,   Germany,   Hong Kong,   Italy,   Korea, Republic of,   Lithuania,   New Zealand,   Poland,   Portugal,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03762850
Other Study ID Numbers  ICMJE 021IGAN17001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Travere Therapeutics, Inc.
Study Sponsor  ICMJE Travere Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Priscila Preciado, MD Travere Therapeutics, Inc.
PRS Account Travere Therapeutics, Inc.
Verification Date June 2021

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