Study of Sparsentan in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS) (DUPLEX)

A Randomized, Multicenter, Double-blind, Parallel, Active-control Study of the Effects of Sparsentan, a Dual Endothelin Receptor and Angiotensin Receptor Blocker, on Renal Outcomes in Patients With Primary FSGS

To determine the long-term nephroprotective potential of treatment with sparsentan as compared to an angiotensin receptor blocker in patients with primary and genetic focal segmental glomerulosclerosis (FSGS).

Study Overview

• Status: Completed
• Conditions: Focal Segmental Glomerulosclerosis
• Intervention / Treatment: Drug: sparsentan; Drug: Irbesartan

Detailed Description

This is a randomized, multicenter, double-blind, parallel, active-control study. Approximately 300 patients aged 8 to 75 years (inclusive) will be enrolled in the study. The study will be conducted in approximately 300 study centers, globally. The investigational drug (sparsentan) is a dual-acting angiotensin receptor blocker and endothelin receptor antagonist. The active control is irbesartan. Patients who meet eligibility criteria will require washout from renin-angiotensin-aldosterone system (RAAS) blockers, if applicable prior to their first dose of study drug.

Patients will be randomly assigned in a 1:1 ratio to receive either sparsentan or active control (irbesartan).

After completing the double-blind portion of the study, patients may participate in the open-label extension for treatment with sparsentan if they meet eligibility criteria.

Primary completion date represents the anticipated completion date of the double-blind portion of the study. Study completion date represents the anticipated completion date of the open-label extension portion of the study.

• Study Type: Interventional
• Enrollment (Actual): 371
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1280AEB
    • Travere Investigational Site
  • Córdoba, Argentina, X5000JHGQ
    • Travere Investigational Site
  • Córdoba, Argentina, X5016LIG
    • Travere Investigational Site
  • Santa Fe, Argentina, S3000
    • Travere Investigational Site
• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Travere Investigational Site
    • New Lambton Heights, New South Wales, Australia, 2305
      • Travere Investigational Site
    • Saint Leonards, New South Wales, Australia, 2065
      • Travere Investigational Site
    • Wollongong, New South Wales, Australia, 2522
      • Travere Investigational Site
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Travere Investigational Site
    • Woolloongabba, Queensland, Australia, 4102
      • Travere Investigational Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Travere Investigational Site
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Travere Investigational Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Travere Investigational Site
• Belgium
  • Leuven, Belgium, 3000
    • Travere Investigational Site
  • Liège, Belgium, 4000
    • Travere Investigational Site
  • Roeselare, Belgium, 8800
    • Travere Investigational Site
• Brazil
  • Botucatu, Brazil, 18618-686
    • Travere Investigational Site
  • Itaquera, Brazil, 08270-120
    • Travere Investigational Site
  • Passo Fundo, Brazil, 99010-080
    • Travere Investigational Site
  • Porto Alegre, Brazil, 90035-903
    • Travere Investigational Site
  • Recife, Brazil, 50670-901
    • Travere Investigational Site
  • Rio de Janeiro, Brazil, 20551-030
    • Travere Investigational Site
  • São Paulo, Brazil, 04038-002
    • Travere Investigational Site
  • São Paulo, Brazil, 05403-000
    • Travere Investigational Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Travere Investigational Site
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • Travere Investigational Site
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Travere Investigational Site
• Croatia
  • Zagreb, Croatia, 10000
    • Travere Investigational Site
• Czechia
  • Nový Jičín, Czechia, 74101
    • Travere Investigational Site
  • Prague
    • Prague, Prague, Czechia, 100 34
      • Travere Investigational Site
    • Prague, Prague, Czechia, 120 00
      • Travere Investigational Site
• Denmark
  • Central Jutland
    • Aarhus, Central Jutland, Denmark, 8200
      • Travere Investigational Site
  • Southern Denmark
    • Kolding, Southern Denmark, Denmark, 6000
      • Travere Investigational Site
• Estonia
  • Tallinn, Estonia, 10617
    • Travere Investigational Site
  • Tartu, Estonia, 50406
    • Travere Investigational Site
• France
  • Bordeaux, France, 33076
    • Travere Investigational Site
  • Clermont-Ferrand, France, 63003
    • Travere Investigational Site
  • Créteil, France, 94000
    • Travere Investigational Site
  • Grenoble, France, 38043
    • Travere Investigational Site
  • Marseille, France, 13005
    • Travere Investigational Site
  • Nice, France, 06001
    • Travere Investigational Site
  • Paris, France, 75010
    • Travere Investigational Site
  • Paris, France, 75015
    • Travere Investigational Site
  • Paris, France, 75743
    • Travere Investigational Site
  • Saint-Priest-en-Jarez, France, 42270
    • Travere Investigational Site
  • Toulouse, France, 31059
    • Travere Investigational Site
  • Valenciennes, France, 59322
    • Travere Investigational Site
• Germany
  • Aachen, Germany, 52074
    • Travere Investigational Site
  • Berlin, Germany, 10117
    • Travere Investigational Site
  • Berlin, Germany, 12203
    • Travere Investigational Site
  • Hanover, Germany, 30625
    • Travere Investigational Site
  • Stuttgart, Germany, 70376
    • Travere Investigational Site
  • Villingen-Schwenningen, Germany, 78052
    • Travere Investigational Site
  • Westfalen
    • Düsseldorf, Westfalen, Germany, 40210
      • Travere Investigational Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Travere Investigational Site
  • Lai Chi Kok, Hong Kong
    • Travere Investigational Site
• Italy
  • Bari, Italy, 70124
    • Travere Investigational Site
  • Bergamo, Italy, 24127
    • Travere Investigational Site
  • Bologna, Italy, 40138
    • Travere Investigational Site
  • Florence, Italy, 50134
    • Travere Investigational Site
  • Genova, Italy, 16132
    • Travere Investigational Site
  • Germaneto, Italy, 88100
    • Travere Investigational Site
  • Lecco, Italy, 23900
    • Travere Investigational Site
  • Milan, Italy, 20122
    • Travere Investigational Site
  • Monza, Italy, 20900
    • Travere Investigational Site
  • Pavia, Italy, 27100
    • Travere Investigational Site
  • Roma, Italy, 168
    • Travere Investigational Site
  • Verona, Italy, 37126
    • Travere Investigational Site
• New Zealand
  • Auckland, New Zealand, 1051
    • Travere Investigational Site
  • Hamilton, New Zealand, 3204
    • Travere Investigational Site
• Poland
  • Lodz, Poland, 93-347
    • Travere Investigational Site
  • Olsztyn, Poland, 10-561
    • Travere Investigational Site
  • Olsztyn, Poland, 10-117
    • Travere Investigational Site
  • Piotrkow Trybunalski, Poland, 97-300
    • Travere Investigational Site
  • Warsaw, Poland, 00-631
    • Travere Investigational Site
  • Warsaw, Poland, 04-749
    • Travere Investigational Site
  • Wroclaw, Poland, 50-556
    • Travere Investigational Site
• Portugal
  • Amadora, Portugal, 2720-276
    • Travere Investigational Site
  • Carnaxide, Portugal, 2790-134
    • Travere Investigational Site
  • Lisbon, Portugal, 1649-035
    • Travere Investigational Site
  • Lisbon, Portugal, 1050-099
    • Travere Investigational Site
  • Loures, Portugal, 2674-514
    • Travere Investigational Site
  • Porto, Portugal, 4200-319
    • Travere Investigational Site
  • Setúbal, Portugal, 2910-446
    • Travere Investigational Site
  • Vila Nova de Gaia, Portugal, 4434-502
    • Travere Investigational Site
• South Korea
  • Busan, South Korea, 47392
    • Travere Investigational Site
  • Daejeon, South Korea, 35015
    • Travere Investigational Site
  • Gyeonggi-do, South Korea, 13620
    • Travere Investigational Site
  • Gyeonggi-do, South Korea, 14068
    • Travere Investigational Site
  • Seoul, South Korea, 3080
    • Travere Investigational Site
  • Seoul, South Korea, 3722
    • Travere Investigational Site
• Spain
  • Badalona, Spain, 8916
    • Travere Investigational Site
  • Barcelona, Spain, 08003
    • Travere Investigational Site
  • Barcelona, Spain, 08025
    • Travere Investigational Site
  • Barcelona, Spain, 08035
    • Travere Investigational Site
  • Barcelona, Spain, 08036
    • Travere Investigational Site
  • Ciudad Real, Spain, 13005
    • Travere Investigational Site
  • Córdoba, Spain, 14004
    • Travere Investigational Site
  • Madrid, Spain, 28040
    • Travere Investigational Site
  • Madrid, Spain, 28041
    • Travere Investigational Site
  • Majadahonda, Spain, 28222
    • Travere Investigational Site
  • Málaga, Spain, 29010
    • Travere Investigational Site
  • Santiago de Compostela, Spain, 15706
    • Travere Investigational Site
  • Seville, Spain, 41009
    • Travere Investigational Site
  • Seville, Spain, 41013
    • Travere Investigational Site
  • Valencia, Spain, 46014
    • Travere Investigational Site
  • Valencia, Spain, 46017
    • Travere Investigational Site
  • Zaragoza, Spain, 50009
    • Travere Investigational Site
  • Balearic Islands
    • Palma de Mallorca, Balearic Islands, Spain, 07120
      • Travere Investigational Site
  • Burela
    • Lugo, Burela, Spain, 27880
      • Travere Investigational Site
  • Valencia
    • Sagunto, Valencia, Spain, 46520
      • Travere Investigational Site
• Sweden
  • Solna, Sweden, SE-171 64
    • Travere Investigational Site
  • Uppsala, Sweden, 75237
    • Travere Investigational Site
  • Uppsala, Sweden, SE-751 85
    • Travere Investigational Site
• Taiwan
  • Hualien City, Taiwan, 970
    • Travere Investigational Site
  • Kaohsiung City, Taiwan, 81362
    • Travere Investigational Site
  • New Taipei City, Taiwan, 235
    • Travere Investigational Site
  • Taichung, Taiwan, 40705
    • Travere Investigational Site
  • Taichung, Taiwan, 404
    • Travere Investigational Site
  • Tainan, Taiwan, 710
    • Travere Investigational Site
  • Taipei, Taiwan, 10048
    • Travere Investigational Site
  • Taipei, Taiwan, 104
    • Travere Investigational Site
  • Taipei, Taiwan, 110
    • Travere Investigational Site
  • Taoyuan District, Taiwan, 333
    • Travere Investigational Site
• United Kingdom
  • Brighton, United Kingdom, BN2 5BE
    • Travere Investigational Site
  • Cambridge, United Kingdom, CB2 0QQ
    • Travere Investigational Site
  • Cardiff, United Kingdom, CF14 4XW
    • Travere Investigational Site
  • Leicester, United Kingdom, LE5 4PW
    • Travere Investigational Site
  • London, United Kingdom, SE5 9RS
    • Travere Investigational Site
  • London, United Kingdom, NW3 2QG
    • Travere Investigational Site
  • Manchester, United Kingdom, M13 9WL
    • Travere Investigational Site
  • Newcastle, United Kingdom, NE7 7DN
    • Travere Investigational Site
  • Reading, United Kingdom, RG1 5AN
    • Travere Investigational Site
  • Salford, United Kingdom, M6 8HD
    • Travere Investigational Site
  • Swansea, United Kingdom, SA6 6NL
    • Travere Investigational Site
  • York, United Kingdom, YO31 8HE
    • Travere Investigational Site
  • London
    • Carshalton, London, United Kingdom, SM5 1AA
      • Travere Investigational Site
    • Whitechapel, London, United Kingdom, E1 1BB
      • Travere Investigational Site
  • Preston
    • Fulwood, Preston, United Kingdom, PR2 9HT
      • Travere Investigational Site
• United States
  • Arizona
    • Mesa, Arizona, United States, 85210
      • Travere Investigational Site
    • Phoenix, Arizona, United States, 85027
      • Travere Investigational Site
  • California
    • Los Angeles, California, United States, 90048
      • Travere Investigational Site
    • Northridge, California, United States, 91324
      • Travere Investigational Site
    • Palo Alto, California, United States, 94304
      • Travere Investigational Site
    • San Diego, California, United States, 92103
      • Travere Investigational Site
    • San Dimas, California, United States, 91773
      • Travere Investigational Site
    • San Francisco, California, United States, 94118
      • Travere Investigational Site
    • Torrance, California, United States, 90502
      • Travere Investigational Site
    • Victorville, California, United States, 92395
      • Travere Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80230
      • Travere Investigational Site
    • Denver, Colorado, United States, 80205
      • Travere Investigational Site
  • Connecticut
    • Middlebury, Connecticut, United States, 06762
      • Travere Investigational Site
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Travere Investigational Site
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Travere Investigational Site
  • Florida
    • Coral Springs, Florida, United States, 33071
      • Travere Investigational Site
    • Fort Lauderdale, Florida, United States, 33308
      • Travere Investigational Site
    • Gainesville, Florida, United States, 32610
      • Travere Investigational Site
    • Miami, Florida, United States, 33136
      • Travere Investigational Site
    • Miami, Florida, United States, 33126
      • Travere Investigational Site
    • Miami, Florida, United States, 33155
      • Travere Investigational Site
    • Ocala, Florida, United States, 34471
      • Travere Investigational Site
    • Orlando, Florida, United States, 32827
      • Travere Investigational Site
    • Port Charlotte, Florida, United States, 33952
      • Travere Investigational Site
    • Temple Terrace, Florida, United States, 33637
      • Travere Investigational Site
    • Winter Park, Florida, United States, 32789
      • Travere Investigational Site
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Travere Investigational Site
  • Idaho
    • Nampa, Idaho, United States, 86387
      • Travere Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Travere Investigational Site
    • Hinsdale, Illinois, United States, 60521
      • Travere Investigational Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Travere Investigational Site
    • Wichita, Kansas, United States, 67214
      • Travere Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Travere Investigational Site
  • Louisiana
    • Monroe, Louisiana, United States, 71201
      • Travere Investigational Site
    • New Orleans, Louisiana, United States, 70121
      • Travere Investigational Site
    • Shreveport, Louisiana, United States, 71101
      • Travere Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Travere Investigational Site
    • Springfield, Massachusetts, United States, 01107
      • Travere Investigational Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Travere Investigational Site
    • Detroit, Michigan, United States, 48202
      • Travere Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Travere Investigational Site
    • Minneapolis, Minnesota, United States, 55455
      • Travere Investigational Site
    • Rochester, Minnesota, United States, 55902
      • Travere Investigational Site
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Travere Investigational Site
    • Kansas City, Missouri, United States, 64111
      • Travere Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89129
      • Travere Investigational Site
    • Reno, Nevada, United States, 89511
      • Travere Investigational Site
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Travere Investigational Site
  • New York
    • Fresh Meadows, New York, United States, 11365
      • Travere Investigational Site
    • New Hyde Park, New York, United States, 11040
      • Travere Investigational Site
    • New York, New York, United States, 10032
      • Travere Investigational Site
    • New York, New York, United States, 10016
      • Travere Investigational Site
    • New York, New York, United States, 10029
      • Travere Investigational Site
    • The Bronx, New York, United States, 10467
      • Travere Investigational Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Travere Investigational Site
    • Durham, North Carolina, United States, 27710
      • Travere Investigational Site
    • Raleigh, North Carolina, United States, 27609
      • Travere Investigational Site
    • Winston-Salem, North Carolina, United States, 27103
      • Travere Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Travere Investigational Site
    • Columbus, Ohio, United States, 43210
      • Travere Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Travere Investigational Site
  • Oregon
    • Roseburg, Oregon, United States, 97471
      • Travere Investigational Site
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Travere Investigational Site
    • Camp Hill, Pennsylvania, United States, 17011
      • Travere Investigational Site
    • Philadelphia, Pennsylvania, United States, 19104
      • Travere Investigational Site
    • Pittsburgh, Pennsylvania, United States, 15224
      • Travere Investigational Site
    • Upland, Pennsylvania, United States, 19013
      • Travere Investigational Site
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Travere Investigational Site
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • Travere Investigational Site
  • Texas
    • Corpus Christi, Texas, United States, 78412
      • Travere Investigational Site
    • Dallas, Texas, United States, 75231
      • Travere Investigational Site
    • Dallas, Texas, United States, 75235
      • Travere Investigational Site
    • Dallas, Texas, United States, 75246
      • Travere Investigational Site
    • El Paso, Texas, United States, 79902
      • Travere Investigational Site
    • Fort Worth, Texas, United States, 76104
      • Travere Investigational Site
    • Houston, Texas, United States, 77054
      • Travere Investigational Site
    • Houston, Texas, United States, 77030
      • Travere Investigational Site
    • Lewisville, Texas, United States, 75057
      • Travere Investigational Site
    • Sherman, Texas, United States, 75090
      • Travere Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84115
      • Travere Investigational Site
    • Salt Lake City, Utah, United States, 84112
      • Travere Investigational Site
    • St. George, Utah, United States, 84790
      • Travere Investigational Site
  • Virginia
    • Hampton, Virginia, United States, 23666
      • Travere Investigational Site
  • Washington
    • Spokane, Washington, United States, 99204
      • Travere Investigational Site
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Travere Investigational Site
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • Travere Investigational Site
    • Wauwatosa, Wisconsin, United States, 53226
      • Travere Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria for the Double-blind Period:

• Sites within the US and UK: The patient is male or female aged 8 to 75 years, inclusive, weighing ≥20 kg at screening
• Sites outside the US and UK: The patient is male or female aged 18 to 75 years, inclusive, weighing ≥20 kg at screening
• Biopsy-proven focal segmental glomerulosclerosis (FSGS) lesion(s) or documentation of a genetic mutation in a podocyte protein associated with FSGS.
• Urine protein/creatinine (UP/C) ≥1.5 g/g (170 mg/mmol) at screening
• eGFR ≥30 mL/min/1.73 m2 at screening.
• Women of childbearing potential must agree to the use of one highly reliable method of contraception from 7 days prior to the first dose of study medication until 90 days after the last dose of study medication, plus one additional barrier method during sexual activity

Key Exclusion Criteria for the Double-blind Period:

• FSGS secondary to another condition
• Positive serological tests of another primary or secondary glomerular disease not consistent with a diagnosis of primary or genetic FSGS
• History of type 1 diabetes mellitus, uncontrolled type 2 diabetes mellitus, or nonfasting blood glucose >180 mg/dL (10.0 mmol/L)
• Treated with rituximab, cyclophosphamide, or abatacept within ≤3 months prior to screening; if taking other chronic immunosuppressive medications, the dosage must be stable prior to screening
• Documented history of heart failure, coronary artery disease, or cerebrovascular disease
• Significant liver disease
• Positive at screening for the human immunodeficiency virus or markers indicating acute or chronic hepatitis B virus infection or hepatitis C infection
• History of malignancy other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma within the past 2 years
• Screening hematocrit value <27% (0.27 L/L) or hemoglobin value <9 g/dL (90 g/L)
• Screening potassium value of >5.5 mEq/L (5.5 mmol/L)
• Extreme obesity (ie, ≥18 years of age with a body mass index (BMI) >40, or is <18 years of age with a BMI in the 99th percentile plus 5 units at screening, in whom there is a causal relationship between obesity and the development of FSGS
• History of alcohol or illicit drug use disorder
• History of serious side effect or allergic response to any angiotensin II antagonist or endothelin receptor antagonist
• Female patient is pregnant, plans to become pregnant during the course of the study, or is breastfeeding.

Key Inclusion Criteria for the Open-label Extension Based on assessments at the Week 108 visit:

• Complete participation in the double-blind period, including the Week 112 visit.
• Patient received blinded study medication through the duration of the double-blind period (ie, did not permanently discontinue study medication)

Key Exclusion Criteria for the Open-label Extension Based on Assessments at Week 108 and 112 visits:

• Progression to end-stage renal disease requiring replacement therapy
• The patient developed criteria for discontinuation between Week 108 and Week 112
• The patient was unable to initiate, or developed contraindications to, treatment with RAAS inhibitors between Week 108 and Week 112
• eGFR ≤20 mL/min/1.73 m2 at Week 108

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sparsentan for double-blind and open-label extension; Sparsentan will be administered as a single oral dose; an initial dose of 400 mg daily titrating up to a target dose of 800 mg, daily	Drug: sparsentan; Double-blind period: target dose of 800 mg daily; Open-label extension: target dose based on dosage from week 114 daily; Other Names: RE-021
Active Comparator: Irbesartan; Irbesartan will be administered as a single oral dose; an initial dose of 150 mg daily titrating up to a target dose of 300 mg, daily	Drug: Irbesartan; target dose of 300 mg daily; Other Names: Irbesartan Tablets USP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Slope of Estimated Glomerular Filtration Rate (eGFR)	The total eGFR slope over 2 years, defined as the slope of eGFR following initiation of randomized treatment (ie, Day 1 to Week 108). Estimates are calculated from a mixed-effects model with treatment, Baseline eGFR, analysis visit, treatment-by-analysis visit, randomization stratification factors as fixed effects, and intercept and slope for each participant as a random effect.	From Day 1 to Week 108
Percentage of Participants Achieving FSGS Partial Remission Endpoint (FPRE)	Percentage of participants achieving FPRE, defined as urine protein-to-creatinine ratio (UP/C) ≤1.5 grams/gram (g/g) (170 milligrams per millimoles [mg/mmol]) and a >40% reduction from Baseline was analyzed using a generalized linear model to model probability of achieving FPRE. Missing responses were imputed prior to analysis using multiple imputation. A generalized linear model with appropriate link function was implemented with Baseline log (UP/C), treatment, analysis visit, treatment by analysis visit interaction, and randomization strata as fixed effects. For estimates of probability of achieving FPRE, risk difference, and odds ratio, binomial distribution with logit link was used. For relative risk, Poisson distribution with log link was used. Using Rubin's approach, estimated treatment effects are combined across all imputations to obtain overall estimates for probabilities.	Week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Slope of eGFR Following the Initial Acute Effect of Randomized Treatment	The chronic eGFR slope over 2 years, defined as the slope of eGFR following the initial acute effect of randomized treatment (ie, Week 6 to Week 108). Estimates were calculated from a mixed-effects model with linear spline (ie, change point at Week 6), which included treatment, Baseline eGFR, time from Baseline (TFB) (weeks), time from change point (TFCP) (weeks), treatment-by-TFB and treatment-by-TFCP interactions, and randomization stratification factors as fixed effects, intercept and slopes as random effects. The slope difference was tested by the null hypothesis that the sum of the treatment-by-TFB and treatment-by-TFCP interactions = 0.	From Week 6 to Week 108
Change From Baseline in eGFR to 4 Weeks Post-cessation of Randomized Treatment	The change from Baseline to 4 weeks post-cessation of randomized treatment (Week 112) was analyzed via an analysis of covariance (ANCOVA) model on the natural log(eGFR) with treatment, Baseline eGFR, and randomization strata as fixed effects. Only participants who completed the 108-week treatment period were included. Estimated LS Mean and 95% CI are converted to percentages as follows: [exponential (LS mean change from baseline in natural log(eGFR)) minus 1] multiplied by 100. Baseline (Day 1) was defined as the last non-missing assessment prior to and including the first administration of study medication in the study including unscheduled assessments. Percent change from Baseline was calculated as "[(Post Baseline minus Baseline value)/ Baseline value] multiplied by 100.	Baseline (Day 1) to Week 112

Collaborators and Investigators

• Sponsor: Travere Therapeutics, Inc.
• Investigators: Study Director: Radko Komers, MD, PhD, Travere Therapeutics, Inc.

Publications and helpful links

General Publications

• 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.
• Obadina M, Wilson S, Derebail VK, Little J. Emerging Therapies and Advances in Sickle Cell Disease with a Focus on Renal Manifestations. Kidney360. 2023 Jul 1;4(7):997-1005. doi: 10.34067/KID.0000000000000162. Epub 2023 May 31.
• Rheault MN. Treatment Approaches for Alport Syndrome. J Am Soc Nephrol. 2026 Jan 1;37(1):172-179. doi: 10.1681/ASN.0000000897. Epub 2025 Sep 12.
• Yee J, Gong W, Inrig J, Rheault MN, Gruber AJ, Bedard PW, Komers R, Trachtman H. Antiproteinuric Effect of Sparsentan in Patients with Genetic-Associated FSGS Enrolled in the DUPLEX Trial. Clin J Am Soc Nephrol. 2025 Dec 23. doi: 10.2215/CJN.0000000948. Online ahead of print. No abstract available.
• 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.
• Rheault MN, Alpers CE, Barratt J, Bieler S, Canetta P, Chae DW, Coppock G, Diva U, Gesualdo L, Heerspink HJL, Inrig JK, Kirsztajn GM, Kohan D, Komers R, Kooienga LA, Lieberman K, Mercer A, Noronha IL, Perkovic V, Radhakrishnan J, Rote W, Rovin B, Tesar V, Trimarchi H, Tumlin J, Wong MG, Trachtman H; DUPRO Steering Committee and DUPLEX Investigators. Sparsentan versus Irbesartan in Focal Segmental Glomerulosclerosis. N Engl J Med. 2023 Dec 28;389(26):2436-2445. doi: 10.1056/NEJMoa2308550. Epub 2023 Nov 3.

Helpful Links

• Corporate Website

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2018
• Primary Completion (Actual): March 20, 2023
• Study Completion (Actual): March 19, 2026

Study Registration Dates

• First Submitted: April 3, 2018
• First Submitted That Met QC Criteria: April 3, 2018
• First Posted (Actual): April 10, 2018

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Glomerulonephritis; Nephritis; Glomerulosclerosis, Focal Segmental; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Polycyclic Compounds; Benzene Derivatives; Tetrazoles; Biphenyl Compounds; Spiro Compounds; Irbesartan; sparsentan
• Other Study ID Numbers: 021FSGS16010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Requests for clinical trial data, including language stating its intended use, should be directed to datarequest@travere.com. If approved, the requested information will be provided to the requestor after signing a data access agreement. Requests can be made following completion of the study and full publication of the study data in a peer reviewed journal for up to 36 months following its publication. Travere reserves the right to decline or recommend modifications to a request if it does not comply with the data sharing policy or if it is determined that the request is made by a biased source.
• IPD Sharing Time Frame: Requests can be made following completion of the study and full publication of the study data in a peer reviewed journal for up to 36 months following its publication.
• IPD Sharing Access Criteria: Requires submission and approval of intended use and a data sharing agreement.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No