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

NCT ID: NCT03762850

Last Updated: 2025-06-10

Study Results

Results available

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Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

406 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-12-11

Study Completion Date

2026-07-31

Brief Summary

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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

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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.

Conditions

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Immunoglobulin A Nephropathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

sparsentan

Intervention Type DRUG

Target dose of 400 mg daily

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.

Group Type ACTIVE_COMPARATOR

irbesartan

Intervention Type DRUG

Target dose of 300 mg daily

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.

Group Type EXPERIMENTAL

sparsentan

Intervention Type DRUG

Target dose of 400 mg daily

Dapagliflozin

Intervention Type DRUG

Target dose of 10 mg daily

sparsentan (Sub Study)

OLE Sub study: Sparsentan will be administered daily as a dose of 400-mg for a period of 12 weeks.

Group Type EXPERIMENTAL

sparsentan

Intervention Type DRUG

Target dose of 400 mg daily

Interventions

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sparsentan

Target dose of 400 mg daily

Intervention Type DRUG

irbesartan

Target dose of 300 mg daily

Intervention Type DRUG

Dapagliflozin

Target dose of 10 mg daily

Intervention Type DRUG

Other Intervention Names

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RE-021 Irbesartan Tablets USP

Eligibility Criteria

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Inclusion Criteria

* 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


* 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


* 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.

Exclusion Criteria

* 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


* 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


* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Travere Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Radko Komers, MD, PhD

Role: STUDY_DIRECTOR

Travere Therapeutics, Inc.

Locations

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Birmingham, Alabama, United States

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Homewood, Alabama, United States

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Glendale, California, United States

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Montebello, California, United States

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Northridge, California, United States

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San Diego, California, United States

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San Diego, California, United States

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Stanford, California, United States

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Denver, Colorado, United States

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Coral Springs, Florida, United States

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Hollywood, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Winter Park, Florida, United States

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Lawrenceville, Georgia, United States

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Nampa, Idaho, United States

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Hinsdale, Illinois, United States

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Muncie, Indiana, United States

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Kansas City, Kansas, United States

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Louisville, Kentucky, United States

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Boston, Massachusetts, United States

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Springfield, Massachusetts, United States

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Worcester, Massachusetts, United States

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Minneapolis, Minnesota, United States

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Reno, Nevada, United States

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Fresh Meadows, New York, United States

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New York, New York, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Philadelphia, Pennsylvania, United States

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Columbia, South Carolina, United States

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El Paso, Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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Lewisville, Texas, United States

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San Antonio, Texas, United States

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Salt Lake City, Utah, United States

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Salt Lake City, Utah, United States

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Tacoma, Washington, United States

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Marshfield, Wisconsin, United States

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Concord, New South Wales, Australia

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Gosford, New South Wales, Australia

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Kingswood, New South Wales, Australia

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New Lambton Heights, New South Wales, Australia

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Randwick, New South Wales, Australia

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St Leonards, New South Wales, Australia

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Birtinya, Queensland, Australia

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Adelaide, South Australia, Australia

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Reservoir, Victoria, Australia

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Nedlands, Western Australia, Australia

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Bonheiden, , Belgium

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Bruges, , Belgium

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Ghent, , Belgium

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Kortrijk, , Belgium

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Liège, , Belgium

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Roeselare, , Belgium

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Osijek, , Croatia

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Zagreb, , Croatia

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Prague, , Czechia

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Prague, , Czechia

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Tallinn, , Estonia

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Tallinn, , Estonia

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Tartu, , Estonia

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Marseille, Bouches-du-Rhone, France

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Montpellier, Herault, France

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Grenoble, Isere, France

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Paris, Paris, France

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Saint-Priest-en-Jarez, Pays de la Loire Region, France

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Clermont-Ferrand, Puy De Dome, France

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Créteil, , France

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Paris, , France

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Villingen-Schwenningen, Baden-Wurttemberg, Germany

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Hanover, Lower Saxony, Germany

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Aachen, North Rhine-Westphalia, Germany

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Düsseldorf, North Rhine-Westphalia, Germany

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Kaiserslautern, Rheinland Palatinate, Germany

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Trier, Rheinland Palatinate, Germany

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Kiel, Schleswig-Holstein, Germany

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Kiel, Schleswig-Holstein, Germany

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Jena, Thuringia, Germany

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Berlin, , 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, Italy

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Milan, Lombardy, Italy

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Bari, , Italy

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Catania, , Italy

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Catanzaro, , Italy

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Lecco, , Italy

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Modena, , Italy

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Pavia, , Italy

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Roma, , Italy

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Torino, , Italy

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Kaunas, , Lithuania

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Vilnius, , Lithuania

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Grafton, Auckland, New Zealand

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Hamilton, , New Zealand

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Hastings, , New Zealand

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New Plymouth, , New Zealand

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Krakow, , Poland

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Lodz, , Poland

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Olsztyn, , Poland

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Warsaw, , Poland

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Wroclaw, , Poland

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Coimbra, , Portugal

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Lisbon, , Portugal

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Loures, , Portugal

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Setúbal, , Portugal

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Vila Nova de Gaia, , Portugal

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Seongnam-si, Gyeonggi-do, South Korea

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Anyang-si, , South Korea

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Busan, , South Korea

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Incheon, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Palma de Mallorca, Balearic Islands, Spain

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Sagunto, Valencia, Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Seville, , Spain

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Valencia, , Spain

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Valencia, , Spain

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Zaragoza, , Spain

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Hualien City, , Taiwan

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Kaohsiung City, , Taiwan

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Kaohsiung City, , Taiwan

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New Taipei City, , Taiwan

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Taichung, , Taiwan

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Reading, Berkshire, United Kingdom

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Cambridge, Cambridgeshire, United Kingdom

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Middlesbrough, Cleveland, United Kingdom

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Derby, Derbyshire, United Kingdom

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Brighton, East Sussex, United Kingdom

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London, Greater London, United Kingdom

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London, Greater London, United Kingdom

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Manchester, Greater Manchester, United Kingdom

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Salford, Greater Manchester, United Kingdom

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Preston, Lancashire, United Kingdom

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Leicester, Leicestershire, United Kingdom

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Edinburgh, Scotland, United Kingdom

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Stoke-on-Trent, Staffordshire, United Kingdom

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Glasgow, Strathclyde, United Kingdom

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Carshalton, Surrey, United Kingdom

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Cardiff, West Glamorgan, United Kingdom

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Birmingham, West Midlands, United Kingdom

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Liverpool, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Countries

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United States Australia Belgium Croatia Czechia Estonia France Germany Hong Kong Italy Lithuania New Zealand Poland Portugal South Korea Spain Taiwan United Kingdom

References

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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.

Reference Type DERIVED
PMID: 38299639 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37931634 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37254256 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37015244 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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http://travere.com

Sponsor Website

Other Identifiers

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2017-004605-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

021IGAN17001

Identifier Type: -

Identifier Source: org_study_id

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