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

A Randomized, Multicenter, Double-blind, Parallel-group, Active-control Study of the Efficacy and Safety of Sparsentan for the Treatment of Immunoglobulin A Nephropathy

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Immunoglobulin A Nephropathy
• Intervention / Treatment: Drug: sparsentan; Drug: irbesartan; Drug: Dapagliflozin

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.

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.

Patients participating in the open-label extension period may be evaluated for eligibility to participate in a randomized, open-label, controlled Sub study evaluating the safety and efficacy of an SGLT2 inhibitor in addition to stable sparsentan treatment (OLE Sub study). The SGLT2 inhibitor, dapagliflozin will be provided as "study medication" for the OLE Sub study. Following completion of the visit 12 weeks after the OLE baseline visit, eligible patients may receive open-label dapagliflozin for at least 12 weeks but up to 24 additional weeks, or through the end of the open-label extension period, whichever is shortest. Approximately 60 patients from the open-label extension period will be enrolled into the OLE Sub study.

• Study Type: Interventional
• Enrollment (Actual): 406
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Travere Investigational Site
    • Gosford, New South Wales, Australia, 2250
      • Travere Investigational Site
    • Kingswood, New South Wales, Australia, 2747
      • Travere Investigational Site
    • New Lambton Heights, New South Wales, Australia, 2305
      • Travere Investigational Site
    • Randwick, New South Wales, Australia, 2031
      • Travere Investigational Site
    • St Leonards, New South Wales, Australia, 2065
      • Travere Investigational Site
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Travere Investigational Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Travere Investigational Site
  • Victoria
    • Reservoir, Victoria, Australia, 3073
      • Travere Investigational Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Travere Investigational Site
• Belgium
  • Bonheiden, Belgium, 2820
    • Travere Investigational Site
  • Bruges, Belgium, 8310
    • Travere Investigational Site
  • Ghent, Belgium, 9000
    • Travere Investigational Site
  • Kortrijk, Belgium, 8500
    • Travere Investigational Site
  • Liège, Belgium, 4000
    • Travere Investigational Site
  • Roeselare, Belgium, 8800
    • Travere Investigational Site
• Croatia
  • Osijek, Croatia, 31000
    • Travere Investigational Site
  • Zagreb, Croatia, 10000
    • Travere Investigational Site
• Czechia
  • Prague, Czechia, 10034
    • Travere Investigational Site
  • Prague, Czechia, 12808
    • Travere Investigational Site
• Estonia
  • Tallinn, Estonia, 10617
    • Travere Investigational Site
  • Tallinn, Estonia, 13419
    • Travere Investigational Site
  • Tartu, Estonia, 50406
    • Travere Investigational Site
• France
  • Créteil, France, 94010
    • Travere Investigational Site
  • Paris, France, 75475
    • Travere Investigational Site
  • Bouches-du-Rhone
    • Marseille, Bouches-du-Rhone, France, 13005
      • Travere Investigational Site
  • Herault
    • Montpellier, Herault, France, 34295
      • Travere Investigational Site
  • Isere
    • Grenoble, Isere, France, 38043
      • Travere Investigational Site
  • Paris
    • Paris, Paris, France, 75015
      • Travere Investigational Site
  • Pays de la Loire Region
    • Saint-Priest-en-Jarez, Pays de la Loire Region, France, 42270
      • Travere Investigational Site
  • Puy De Dome
    • Clermont-Ferrand, Puy De Dome, France, 63003
      • Travere Investigational Site
• Germany
  • Berlin, Germany, 10117
    • Travere Investigational Site
  • Baden-Wurttemberg
    • Villingen-Schwenningen, Baden-Wurttemberg, Germany, 78052
      • Travere Investigational Site
  • Lower Saxony
    • Hanover, Lower Saxony, Germany, 30625
      • Travere Investigational Site
  • North Rhine-Westphalia
    • Aachen, North Rhine-Westphalia, Germany, 52074
      • Travere Investigational Site
    • Düsseldorf, North Rhine-Westphalia, Germany, 40210
      • Travere Investigational Site
  • Rheinland Palatinate
    • Kaiserslautern, Rheinland Palatinate, Germany, 67655
      • Travere Investigational Site
    • Trier, Rheinland Palatinate, Germany, 54292
      • Travere Investigational Site
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Travere Investigational Site
    • Kiel, Schleswig-Holstein, Germany, 23538
      • Travere Investigational Site
  • Thuringia
    • Jena, Thuringia, Germany, 07747
      • Travere Investigational Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Travere Investigational Site
  • Kowloon
    • Kwun Tong, Kowloon, Hong Kong
      • Travere Investigational Site
    • Lai Chi Kok, Kowloon, Hong Kong
      • Travere Investigational Site
  • New Territories
    • Shatin, New Territories, Hong Kong
      • Travere Investigational Site
    • Tsuen Wan, New Territories, Hong Kong
      • Travere Investigational Site
• Italy
  • Bari, Italy, 70124
    • Travere Investigational Site
  • Catania, Italy, 95123
    • Travere Investigational Site
  • Catanzaro, Italy, 88100
    • Travere Investigational Site
  • Lecco, Italy, 23900
    • Travere Investigational Site
  • Modena, Italy, 41124
    • Travere Investigational Site
  • Pavia, Italy, 27100
    • Travere Investigational Site
  • Roma, Italy, 00168
    • Travere Investigational Site
  • Torino, Italy, 10126
    • Travere Investigational Site
  • Bergamo
    • Ranica, Bergamo, Italy, 24020
      • Travere Investigational Site
  • Lombardy
    • Milan, Lombardy, Italy, 20162
      • Travere Investigational Site
• Lithuania
  • Kaunas, Lithuania, LT-50009
    • Travere Investigational Site
  • Vilnius, Lithuania, LT-08661
    • Travere Investigational Site
• New Zealand
  • Hamilton, New Zealand, 3200
    • Travere Investigational Site
  • Hastings, New Zealand, 4120
    • Travere Investigational Site
  • New Plymouth, New Zealand, 4310
    • Travere Investigational Site
  • Auckland
    • Grafton, Auckland, New Zealand, 1142
      • Travere Investigational Site
• Poland
  • Krakow, Poland, 31-559
    • Travere Investigational Site
  • Lodz, Poland, 93-347
    • Travere Investigational Site
  • Olsztyn, Poland, 10-124
    • Travere Investigational Site
  • Olsztyn, Poland, 10-561
    • Travere Investigational Site
  • Warsaw, Poland, 04-749
    • Travere Investigational Site
  • Wroclaw, Poland, 50-566
    • Travere Investigational Site
• Portugal
  • Coimbra, Portugal, 3000-075
    • Travere Investigational Site
  • Lisbon, Portugal, 1649-035
    • Travere Investigational Site
  • Lisbon, Portugal, 1069-166
    • Travere Investigational Site
  • Loures, Portugal, 2674-514
    • Travere Investigational Site
  • Setúbal, Portugal, 2910-446
    • Travere Investigational Site
  • Vila Nova de Gaia, Portugal, 4434-502
    • Travere Investigational Site
• South Korea
  • Anyang-si, South Korea, 14068
    • Travere Investigational Site
  • Busan, South Korea, 47392
    • Travere Investigational Site
  • Incheon, South Korea, 21565
    • Travere Investigational Site
  • Seoul, South Korea, 02841
    • Travere Investigational Site
  • Seoul, South Korea, 03080
    • Travere Investigational Site
  • Seoul, South Korea, 06273
    • Travere Investigational Site
  • Seoul, South Korea, 110-746
    • Travere Investigational Site
  • Seoul, South Korea, 120-752
    • Travere Investigational Site
  • Seoul, South Korea, 135-710
    • Travere Investigational Site
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea, 13620
      • Travere Investigational Site
• Spain
  • Barcelona, Spain, 08003
    • Travere Investigational Site
  • Barcelona, Spain, 08025
    • Travere Investigational Site
  • Barcelona, Spain, 08035
    • Travere Investigational Site
  • Barcelona, Spain, 08036
    • Travere Investigational Site
  • Madrid, Spain, 28007
    • Travere Investigational Site
  • Madrid, Spain, 28040
    • Travere Investigational Site
  • Madrid, Spain, 28041
    • Travere Investigational Site
  • Seville, Spain, 41009
    • 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
  • Valencia
    • Sagunto, Valencia, Spain, 46520
      • Travere Investigational Site
• Taiwan
  • Hualien City, Taiwan, 970
    • Travere Investigational Site
  • Kaohsiung City, Taiwan, 81362
    • Travere Investigational Site
  • Kaohsiung City, Taiwan, 807
    • Travere Investigational Site
  • New Taipei City, Taiwan, 220
    • Travere Investigational Site
  • Taichung, Taiwan, 40705
    • Travere Investigational Site
• United Kingdom
  • Liverpool, United Kingdom, L9 7AL
    • Travere Investigational Site
  • London, United Kingdom, SE5 9RS
    • Travere Investigational Site
  • London, United Kingdom, E1 1FR
    • Travere Investigational Site
  • Berkshire
    • Reading, Berkshire, United Kingdom, RG1 5AN
      • Travere Investigational Site
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Travere Investigational Site
  • Cleveland
    • Middlesbrough, Cleveland, United Kingdom, TS4 3BW
      • Travere Investigational Site
  • Derbyshire
    • Derby, Derbyshire, United Kingdom, DE22 3DT
      • Travere Investigational Site
  • East Sussex
    • Brighton, East Sussex, United Kingdom, BN2 5BE
      • Travere Investigational Site
  • Greater London
    • London, Greater London, United Kingdom, E1 4AT
      • Travere Investigational Site
    • London, Greater London, United Kingdom, SE1 9RT
      • Travere Investigational Site
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M13 9WL
      • Travere Investigational Site
    • Salford, Greater Manchester, United Kingdom, M6 8HD
      • Travere Investigational Site
  • Lancashire
    • Preston, Lancashire, United Kingdom, PR2 9HT
      • Travere Investigational Site
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE5 4PW
      • Travere Investigational Site
  • Scotland
    • Edinburgh, Scotland, United Kingdom, EH16 4SA
      • Travere Investigational Site
  • Staffordshire
    • Stoke-on-Trent, Staffordshire, United Kingdom, ST4 6QG
      • Travere Investigational Site
  • Strathclyde
    • Glasgow, Strathclyde, United Kingdom, G11 6NT
      • Travere Investigational Site
  • Surrey
    • Carshalton, Surrey, United Kingdom, SM5 1AA
      • Travere Investigational Site
  • West Glamorgan
    • Cardiff, West Glamorgan, United Kingdom, CF14 4XW
      • Travere Investigational Site
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B9 5SS
      • Travere Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Travere Investigational Site
    • Homewood, Alabama, United States, 35209
      • Travere Investigational Site
  • California
    • Glendale, California, United States, 91206
      • Travere Investigational Site
    • Montebello, California, United States, 90640
      • Travere Investigational Site
    • Northridge, California, United States, 91324
      • Travere Investigational Site
    • San Diego, California, United States, 92103-6204
      • Travere Investigational Site
    • San Diego, California, United States, 92103
      • Travere Investigational Site
    • Stanford, California, United States, 94205
      • Travere Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80230
      • Travere Investigational Site
  • Florida
    • Coral Springs, Florida, United States, 33071
      • Travere Investigational Site
    • Hollywood, Florida, United States, 33021
      • Travere Investigational Site
    • Miami, Florida, United States, 33136
      • Travere Investigational Site
    • Miami, Florida, United States, 33186
      • 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, 83687
      • Travere Investigational Site
  • Illinois
    • Hinsdale, Illinois, United States, 60521
      • Travere Investigational Site
  • Indiana
    • Muncie, Indiana, United States, 47303
      • Travere Investigational Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Travere Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Travere Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Travere Investigational Site
    • Springfield, Massachusetts, United States, 01104
      • Travere Investigational Site
    • Worcester, Massachusetts, United States, 01608
      • Travere Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Travere Investigational Site
  • Nevada
    • Reno, Nevada, United States, 89511
      • Travere Investigational Site
  • New York
    • Fresh Meadows, New York, United States, 11365
      • Travere Investigational Site
    • New York, New York, United States, 10032
      • Travere Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Travere Investigational Site
    • Columbus, Ohio, United States, 43210
      • Travere Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Travere Investigational Site
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Travere Investigational Site
  • Texas
    • El Paso, Texas, United States, 79935
      • Travere Investigational Site
    • Fort Worth, Texas, United States, 76104
      • Travere Investigational Site
    • Houston, Texas, United States, 77054
      • Travere Investigational Site
    • Lewisville, Texas, United States, 75057
      • Travere Investigational Site
    • San Antonio, Texas, United States, 78207
      • Travere Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84115
      • Travere Investigational Site
    • Salt Lake City, Utah, United States, 84132
      • Travere Investigational Site
  • Washington
    • Tacoma, Washington, United States, 98405
      • Travere Investigational Site
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • Travere Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Key Inclusion Criteria for the OLE Sparsentan + SGLT2 Inhibitor Sub study:

• Participating in the open-label extension and is willing and able to provide signed informed consent for participation in the open-label extension period Sub study
• A urine protein excretion value of ≥0.3 g/day.
• An eGFR of ≥25 mL/min/1.73m2
• On a stable dose of sparsentan for ≥8 weeks in the open-label extension period that is the maximum tolerated dose.

Key Exclusion Criteria for the OLE Sparsentan + SGLT2 Inhibitor Sub study:

• Progressed to ESRD requiring RRT
• Initiated or changed dose of a systemic immunosuppressive medication (including systemic steroids) within 12 weeks
• Taking an SGLT2 inhibitor within 12 weeks

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sparsentan; Double-blind: 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.	Drug: sparsentan; Target dose of 400 mg daily; Other Names: RE-021
Active Comparator: irbesartan; Double-blind: 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.	Drug: irbesartan; Target dose of 300 mg daily; Other Names: Irbesartan Tablets USP
Experimental: dapagliflozin + sparsentan (Sub study); OLE Sub study: Dapagliflozin will be administered daily as a 5-mg oral tablet, in addition to 400-mg of Sparsentan, for a period of 12 weeks.	Drug: sparsentan; Target dose of 400 mg daily; Other Names: RE-021; Drug: Dapagliflozin; Target dose of 10 mg daily
Experimental: sparsentan (Sub Study); OLE Sub study: Sparsentan will be administered daily as a dose of 400-mg for a period of 12 weeks.	Drug: sparsentan; Target dose of 400 mg daily; Other Names: RE-021

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in the Urine Protein/Creatinine (UP/C) at Week 36	24-hour urine sample was collected for analysis of UP/C via a mixed-model repeated-measures (MMRM) analysis. Missing responses were imputed prior to analysis using multiple imputation. Change from Baseline during the double-blind period in UP/C on the log scale was the dependent variable. Log Baseline UP/C was included as a covariate along with fixed effects for randomized treatment, time (ie, nominal visit in weeks), randomized treatment-by-time interaction, and randomization strata with participants as random effect. Estimates in log scale were back transformed. Baseline was defined as the last non-missing observation on or prior to the start of the dosing. Using Rubin's approach, estimated treatment effects are combined across all imputations to obtain overall estimates.	Baseline (Day 1) and at Week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Slope of Estimated Glomerular Filtration Rate (eGFR) Over a 110-week Period	The rate of change in eGFR from Day 1 to Week 110 (ie, over 110 weeks) was analyzed via a mixed-model random coefficients analysis. Missing responses were imputed prior to analysis using multiple imputation. Fixed effects for randomized treatment, Baseline eGFR, time (in weeks), randomized treatment-by-time interaction, and randomization strata were included. In addition, the model also included a random intercept and random slope for each participant. Using Rubin's approach, the estimated treatment effects are combined across all imputations to obtain the overall estimates.	From Day 1 to Week 110
Annualized Slope of eGFR Following the Initial Acute Effect of Randomized Treatment (Chronic Slope)	The rate of change in eGFR from Week 6 to Week 110 (ie, over 104 weeks following the initial acute effect of randomized therapy) was analyzed via a mixed-model random coefficients analysis. Missing responses were imputed prior to analysis using multiple imputation. Fixed effects for randomized treatment, Baseline eGFR, time (in weeks), randomized treatment-by-time interaction, and randomization strata were included. In addition, the model also included a random intercept and random slope for each participant. Using Rubin's approach, the estimated treatment effects are combined across all imputations to obtain the overall estimates.	From Week 6 to Week 110 post randomization

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Tunnicliffe DJ, Reid S, Craig JC, Samuels JA, Molony DA, Strippoli GF. Non-immunosuppressive treatment for IgA nephropathy. Cochrane Database Syst Rev. 2024 Feb 1;2(2):CD003962. doi: 10.1002/14651858.CD003962.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.
• Heerspink HJL, Rovin BH, Komers R, Hendry B, Mercer A, Preciado P, Murphy E, Tesar V. Association between Complete Proteinuria Remission and Kidney Function in the Phase 3 PROTECT Trial of Sparsentan in IgA Nephropathy. Clin J Am Soc Nephrol. 2026 Apr 1;21(4):578-592. doi: 10.2215/CJN.0000000961. Epub 2025 Dec 22.
• Rovin BH, Barratt J, Heerspink HJL, Alpers CE, Bieler S, Chae DW, Diva UA, Floege J, Gesualdo L, Inrig JK, Kohan DE, Komers R, Kooienga LA, Lafayette R, Maes B, Malecki R, Mercer A, Noronha IL, Oh SW, Peh CA, Praga M, Preciado P, Radhakrishnan J, Rheault MN, Rote WE, Tang SCW, Tesar V, Trachtman H, Trimarchi H, Tumlin JA, Wong MG, Perkovic V; DUPRO steering committee and PROTECT Investigators. Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial. Lancet. 2023 Dec 2;402(10417):2077-2090. doi: 10.1016/S0140-6736(23)02302-4. Epub 2023 Nov 3.
• Heerspink HJL, Radhakrishnan J, Alpers CE, Barratt J, Bieler S, Diva U, Inrig J, Komers R, Mercer A, Noronha IL, Rheault MN, Rote W, Rovin B, Trachtman H, Trimarchi H, Wong MG, Perkovic V; PROTECT Investigators. Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial. Lancet. 2023 May 13;401(10388):1584-1594. doi: 10.1016/S0140-6736(23)00569-X. Epub 2023 Apr 1.

Helpful Links

• Sponsor Website

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2018
• Primary Completion (Actual): August 7, 2023
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: November 27, 2018
• First Submitted That Met QC Criteria: November 30, 2018
• First Posted (Actual): December 4, 2018

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 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; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Glomerulonephritis, IGA; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Polycyclic Compounds; Benzene Derivatives; Tetrazoles; Biphenyl Compounds; Spiro Compounds; Irbesartan; dapagliflozin; sparsentan
• Other Study ID Numbers: 021IGAN17001; 2017-004605-41 (EudraCT Number)

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