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
2 other identifiers
interventional
406
17 countries
159
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Dec 2018
Longer than P75 for phase_3
159 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 27, 2018
CompletedFirst Posted
Study publicly available on registry
December 4, 2018
CompletedStudy Start
First participant enrolled
December 11, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 7, 2023
CompletedResults Posted
Study results publicly available
July 3, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2026
ExpectedApril 20, 2026
March 1, 2026
4.7 years
November 27, 2018
June 11, 2024
March 31, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
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 Outcomes (2)
Total Slope of Estimated Glomerular Filtration Rate (eGFR) Over a 110-week Period
From Day 1 to Week 110
Annualized Slope of eGFR Following the Initial Acute Effect of Randomized Treatment (Chronic Slope)
From Week 6 to Week 110 post randomization
Study Arms (4)
sparsentan
EXPERIMENTALDouble-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.
irbesartan
ACTIVE COMPARATORDouble-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.
dapagliflozin + sparsentan (Sub study)
EXPERIMENTALOLE 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.
sparsentan (Sub Study)
EXPERIMENTALOLE Sub study: Sparsentan will be administered daily as a dose of 400-mg for a period of 12 weeks.
Interventions
Target dose of 400 mg daily
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (162)
Travere Investigational Site
Birmingham, Alabama, 35233, United States
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Homewood, Alabama, 35209, United States
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Glendale, California, 91206, United States
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Montebello, California, 90640, United States
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Northridge, California, 91324, United States
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San Diego, California, 92103-6204, United States
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San Diego, California, 92103, United States
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Stanford, California, 94205, United States
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Denver, Colorado, 80230, United States
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Coral Springs, Florida, 33071, United States
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Hollywood, Florida, 33021, United States
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Miami, Florida, 33136, United States
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Miami, Florida, 33186, United States
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Winter Park, Florida, 32789, United States
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Lawrenceville, Georgia, 30046, United States
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Nampa, Idaho, 83687, United States
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Hinsdale, Illinois, 60521, United States
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Muncie, Indiana, 47303, United States
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Kansas City, Kansas, 66160, United States
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Louisville, Kentucky, 40202, United States
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Boston, Massachusetts, 02215, United States
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Springfield, Massachusetts, 01104, United States
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Worcester, Massachusetts, 01608, United States
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Minneapolis, Minnesota, 55404, United States
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Reno, Nevada, 89511, United States
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Fresh Meadows, New York, 11365, United States
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New York, New York, 10032, United States
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Cleveland, Ohio, 44106, United States
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Columbus, Ohio, 43210, United States
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Philadelphia, Pennsylvania, 19104, United States
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Columbia, South Carolina, 29203, United States
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El Paso, Texas, 79935, United States
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Fort Worth, Texas, 76104, United States
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Houston, Texas, 77054, United States
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Lewisville, Texas, 75057, United States
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San Antonio, Texas, 78207, United States
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Salt Lake City, Utah, 84115, United States
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Salt Lake City, Utah, 84132, United States
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Tacoma, Washington, 98405, United States
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Marshfield, Wisconsin, 54449, United States
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Concord, New South Wales, 2139, Australia
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Gosford, New South Wales, 2250, Australia
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Kingswood, New South Wales, 2747, Australia
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New Lambton Heights, New South Wales, 2305, Australia
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Randwick, New South Wales, 2031, Australia
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St Leonards, New South Wales, 2065, Australia
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Birtinya, Queensland, 4575, Australia
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Adelaide, South Australia, 5000, Australia
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Reservoir, Victoria, 3073, Australia
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Nedlands, Western Australia, 6009, Australia
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Bonheiden, 2820, Belgium
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Bruges, 8310, Belgium
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Ghent, 9000, Belgium
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Kortrijk, 8500, Belgium
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Liège, 4000, Belgium
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Roeselare, 8800, Belgium
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Osijek, 31000, Croatia
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Zagreb, 10000, Croatia
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Prague, 10034, Czechia
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Prague, 12808, Czechia
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Tallinn, 10617, Estonia
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Tallinn, 13419, Estonia
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Tartu, 50406, Estonia
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Marseille, Bouches-du-Rhone, 13005, France
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Montpellier, Herault, 34295, France
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Grenoble, Isere, 38043, France
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Paris, Paris, 75015, France
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Saint-Priest-en-Jarez, Pays de la Loire Region, 42270, France
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Clermont-Ferrand, Puy De Dome, 63003, France
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Créteil, 94010, France
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Paris, 75475, France
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Villingen-Schwenningen, Baden-Wurttemberg, 78052, Germany
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Hanover, Lower Saxony, 30625, Germany
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Aachen, North Rhine-Westphalia, 52074, Germany
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DĂ¼sseldorf, North Rhine-Westphalia, 40210, Germany
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Kaiserslautern, Rheinland Palatinate, 67655, Germany
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Trier, Rheinland Palatinate, 54292, Germany
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Kiel, Schleswig-Holstein, 23538, Germany
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Kiel, Schleswig-Holstein, 24105, Germany
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Jena, Thuringia, 07747, Germany
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Berlin, 10117, Germany
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Kwun Tong, Kowloon, Hong Kong
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Lai Chi Kok, Kowloon, Hong Kong
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Shatin, New Territories, Hong Kong
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Tsuen Wan, New Territories, Hong Kong
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Hong Kong, Hong Kong
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Ranica, Bergamo, 24020, Italy
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Milan, Lombardy, 20162, Italy
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Bari, 70124, Italy
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Catania, 95123, Italy
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Catanzaro, 88100, Italy
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Lecco, 23900, Italy
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Modena, 41124, Italy
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Pavia, 27100, Italy
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Roma, 00168, Italy
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Torino, 10126, Italy
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Kaunas, LT-50009, Lithuania
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Vilnius, LT-08661, Lithuania
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Grafton, Auckland, 1142, New Zealand
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Hamilton, 3200, New Zealand
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Hastings, 4120, New Zealand
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New Plymouth, 4310, New Zealand
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Krakow, 31-559, Poland
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Lodz, 93-347, Poland
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Olsztyn, 10-124, Poland
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Olsztyn, 10-561, Poland
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Warsaw, 04-749, Poland
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Wroclaw, 50-566, Poland
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Coimbra, 3000-075, Portugal
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Lisbon, 1069-166, Portugal
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Lisbon, 1649-035, Portugal
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Loures, 2674-514, Portugal
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SetĂºbal, 2910-446, Portugal
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Vila Nova de Gaia, 4434-502, Portugal
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Seongnam-si, Gyeonggi-do, 13620, South Korea
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Anyang-si, 14068, South Korea
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Busan, 47392, South Korea
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Incheon, 21565, South Korea
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Seoul, 02841, South Korea
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Seoul, 03080, South Korea
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Seoul, 06273, South Korea
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Seoul, 110-746, South Korea
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Seoul, 120-752, South Korea
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Seoul, 135-710, South Korea
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Palma de Mallorca, Balearic Islands, 07120, Spain
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Sagunto, Valencia, 46520, Spain
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Barcelona, 08003, Spain
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Barcelona, 08025, Spain
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Barcelona, 08035, Spain
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Barcelona, 08036, Spain
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Madrid, 28007, Spain
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Madrid, 28040, Spain
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Madrid, 28041, Spain
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Seville, 41009, Spain
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Valencia, 46014, Spain
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Valencia, 46017, Spain
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Zaragoza, 50009, Spain
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Hualien City, 970, Taiwan
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Kaohsiung City, 807, Taiwan
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Kaohsiung City, 81362, Taiwan
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New Taipei City, 220, Taiwan
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Taichung, 40705, Taiwan
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Reading, Berkshire, RG1 5AN, United Kingdom
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Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom
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Middlesbrough, Cleveland, TS4 3BW, United Kingdom
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Derby, Derbyshire, DE22 3DT, United Kingdom
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Brighton, East Sussex, BN2 5BE, United Kingdom
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London, Greater London, E1 4AT, United Kingdom
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London, Greater London, SE1 9RT, United Kingdom
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Manchester, Greater Manchester, M13 9WL, United Kingdom
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Salford, Greater Manchester, M6 8HD, United Kingdom
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Preston, Lancashire, PR2 9HT, United Kingdom
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Leicester, Leicestershire, LE5 4PW, United Kingdom
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Edinburgh, Scotland, EH16 4SA, United Kingdom
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Stoke-on-Trent, Staffordshire, ST4 6QG, United Kingdom
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Glasgow, Strathclyde, G11 6NT, United Kingdom
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Carshalton, Surrey, SM5 1AA, United Kingdom
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Cardiff, West Glamorgan, CF14 4XW, United Kingdom
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Birmingham, West Midlands, B9 5SS, United Kingdom
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Liverpool, L9 7AL, United Kingdom
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London, E1 1FR, United Kingdom
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London, SE5 9RS, United Kingdom
Related Publications (5)
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.
PMID: 41428405DERIVEDTunnicliffe 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.
PMID: 38299639DERIVEDRovin 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.
PMID: 37931634DERIVEDObadina 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.
PMID: 37254256DERIVEDHeerspink 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.
PMID: 37015244DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Travere Therapeutics Call Center
- Organization
- Travere Therapeutics, Inc
Study Officials
- STUDY DIRECTOR
Radko Komers, MD, PhD
Travere Therapeutics, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 27, 2018
First Posted
December 4, 2018
Study Start
December 11, 2018
Primary Completion
August 7, 2023
Study Completion (Estimated)
July 1, 2026
Last Updated
April 20, 2026
Results First Posted
July 3, 2024
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- 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.
- Access Criteria
- Requires submission and approval of intended use and a data sharing agreement.
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.