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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03762850
Other study ID # 021IGAN17001
Secondary ID 2017-004605-41
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date December 11, 2018
Est. completion date July 2026

Study information

Verified date February 2023
Source Travere Therapeutics, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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).


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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 380
Est. completion date July 2026
Est. primary completion date August 7, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design


Intervention

Drug:
sparsentan
Target dose of 400 mg daily
irbesartan
Target dose of 300 mg daily
Dapagliflozin
Target dose of 10 mg daily

Locations

Country Name City State
Australia Travere Investigational Site Adelaide South Australia
Australia Travere Investigational Site Birtinya Queensland
Australia Travere Investigational Site Concord New South Wales
Australia Travere Investigational Site Gosford New South Wales
Australia Travere Investigational Site Kingswood New South Wales
Australia Travere Investigational Site Nedlands Western Australia
Australia Travere Investigational Site New Lambton Heights New South Wales
Australia Travere Investigational Site Randwick New South Wales
Australia Travere Investigational Site Reservoir Victoria
Australia Travere Investigational Site St Leonards New South Wales
Belgium Travere Investigational Site Bonheiden
Belgium Travere Investigational Site Brugge
Belgium Travere Investigational Site Gent
Belgium Travere Investigational Site Kortrijk
Belgium Travere Investigational Site Liège
Belgium Travere Investigational Site Roeselare
Croatia Travere Investigational Site Osijek
Croatia Travere Investigational Site Zagreb
Czechia Travere Investigational Site Praha 10
Czechia Travere Investigational Site Praha 2
Estonia Travere Investigational Site Tallinn
Estonia Travere Investigational Site Tallinn
Estonia Travere Investigational Site Tartu
France Travere Investigational Site Clermont Ferrand Cedex Puy De Dome
France Travere Investigational Site Créteil
France Travere Investigational Site Grenoble Cedex 9 Isere
France Travere Investigational Site Marseille Bouches-du-Rhone
France Travere Investigational Site Montpellier Cedex 5 Herault
France Travere Investigational Site Paris
France Travere Investigational Site Paris Cedex 15 Paris
France Travere Investigational Site Saint-Priest-en-Jarez Loire
Germany Travere Investigational Site Aachen North Rhine Westphalia
Germany Travere Investigational Site Berlin
Germany Travere Investigational Site Duesseldorf Nordrhein Westfalen
Germany Travere Investigational Site Hanover Lower Saxony
Germany Travere Investigational Site Jena Thueringen
Germany Travere Investigational Site Kaiserslautern Rheinland Palatinate
Germany Travere Investigational Site Kiel Schleswig Holstein
Germany Travere Investigational Site Kiel Schleswig-Holstein
Germany Travere Investigational Site Trier Rheinland Palatinate
Germany Travere Investigational Site Villingen-Schwenningen Baden Wuerttemberg
Hong Kong Travere Investigational Site Hong Kong
Hong Kong Travere Investigational Site Kwun Tong Kowloon
Hong Kong Travere Investigational Site Lai Chi Kok Kowloon
Hong Kong Travere Investigational Site Shatin New Territories
Hong Kong Travere Investigational Site Tsuen Wan New Territories
Italy Travere Investigational Site Bari
Italy Travere Investigational Site Catania
Italy Travere Investigational Site Catanzaro
Italy Travere Investigational Site Lecco
Italy Travere Investigational Site Milan Lombardia
Italy Travere Investigational Site Modena
Italy Travere Investigational Site Pavia
Italy Travere Investigational Site Ranica Bergamo
Italy Travere Investigational Site Roma
Italy Travere Investigational Site Torino
Korea, Republic of Travere Investigational Site Anyang-Si
Korea, Republic of Travere Investigational Site Busan
Korea, Republic of Travere Investigational Site Incheon
Korea, Republic of Travere Investigational Site Seongnam-si Gyeonggi-do
Korea, Republic of Travere Investigational Site Seoul
Korea, Republic of Travere Investigational Site Seoul
Korea, Republic of Travere Investigational Site Seoul
Korea, Republic of Travere Investigational Site Seoul
Korea, Republic of Travere Investigational Site Seoul
Korea, Republic of Travere Investigational Site Seoul
Lithuania Travere Investigational Site Kaunas
Lithuania Travere Investigational Site Vilnius
New Zealand Travere Investigational Site Grafton Auckland
New Zealand Travere Investigational Site Hamilton
New Zealand Travere Investigational Site Hastings
New Zealand Travere Investigational Site New Plymouth
Poland Travere Investigational Site Kraków
Poland Travere Investigational Site Lódz
Poland Travere Investigational Site Olsztyn
Poland Travere Investigational Site Olsztyn
Poland Travere Investigational Site Warszawa
Poland Travere Investigational Site Wroclaw
Portugal Travere Investigational Site Coimbra
Portugal Travere Investigational Site Lisboa
Portugal Travere Investigational Site Lisboa
Portugal Travere Investigational Site Loures
Portugal Travere Investigational Site Setúbal
Portugal Travere Investigational Site Vila Nova De Gaia
Spain Travere Investigational Site Barcelona
Spain Travere Investigational Site Barcelona
Spain Travere Investigational Site Barcelona
Spain Travere Investigational Site Barcelona
Spain Travere Investigational Site Madrid
Spain Travere Investigational Site Madrid
Spain Travere Investigational Site Madrid
Spain Travere Investigational Site Palma De Mallorca Baleares
Spain Travere Investigational Site Sagunto Valencia
Spain Travere Investigational Site Sevilla
Spain Travere Investigational Site Valencia
Spain Travere Investigational Site Valencia
Spain Travere Investigational Site Zaragoza
Taiwan Travere Investigational Site Hualien City
Taiwan Travere Investigational Site Kaohsiung
Taiwan Travere Investigational Site Kaohsiung
Taiwan Travere Investigational Site New Taipei City
Taiwan Travere Investigational Site Taichung
United Kingdom Travere Investigational Site Birmingham West Midlands
United Kingdom Travere Investigational Site Brighton East Sussex
United Kingdom Travere Investigational Site Cambridge Cambridgeshire
United Kingdom Travere Investigational Site Cardiff West Glamorgan
United Kingdom Travere Investigational Site Carshalton Surrey
United Kingdom Travere Investigational Site Derby Derbyshire
United Kingdom Travere Investigational Site Edinburgh Scotland
United Kingdom Travere Investigational Site Glasgow Strathclyde
United Kingdom Travere Investigational Site Leicester Leicestershire
United Kingdom Travere Investigational Site Liverpool
United Kingdom Travere Investigational Site London
United Kingdom Travere Investigational Site London
United Kingdom Travere Investigational Site London Greater London
United Kingdom Travere Investigational Site London Greater London
United Kingdom Travere Investigational Site Manchester Greater Manchester
United Kingdom Travere Investigational Site Middlesbrough Cleveland
United Kingdom Travere Investigational Site Preston Lancashire
United Kingdom Travere Investigational Site Reading Berkshire
United Kingdom Travere Investigational Site Salford Greater Manchester
United Kingdom Travere Investigational Site Stoke-on-Trent Staffordshire
United States Travere Investigational Site Birmingham Alabama
United States Travere Investigational Site Boston Massachusetts
United States Travere Investigational Site Cleveland Ohio
United States Travere Investigational Site Columbia South Carolina
United States Travere Investigational Site Columbus Ohio
United States Travere Investigational Site Coral Springs Florida
United States Travere Investigational Site Denver Colorado
United States Travere Investigational Site El Paso Texas
United States Travere Investigational Site Fort Worth Texas
United States Travere Investigational Site Fresh Meadows New York
United States Travere Investigational Site Glendale California
United States Travere Investigational Site Hinsdale Illinois
United States Travere Investigational Site Hollywood Florida
United States Travere Investigational Site Homewood Alabama
United States Travere Investigational Site Houston Texas
United States Travere Investigational Site Kansas City Kansas
United States Travere Investigational Site Lawrenceville Georgia
United States Travere Investigational Site Lewisville Texas
United States Travere Investigational Site Louisville Kentucky
United States Travere Investigational Site Marshfield Wisconsin
United States Travere Investigational Site Miami Florida
United States Travere Investigational Site Miami Florida
United States Travere Investigational Site Minneapolis Minnesota
United States Travere Investigational Site Montebello California
United States Travere Investigational Site Muncie Indiana
United States Travere Investigational Site Nampa Idaho
United States Travere Investigational Site New York New York
United States Travere Investigational Site Northridge California
United States Travere Investigational Site Philadelphia Pennsylvania
United States Travere Investigational Site Reno Nevada
United States Travere Investigational Site Salt Lake City Utah
United States Travere Investigational Site Salt Lake City Utah
United States Travere Investigational Site San Antonio Texas
United States Travere Investigational Site San Diego California
United States Travere Investigational Site San Diego California
United States Travere Investigational Site Springfield Massachusetts
United States Travere Investigational Site Stanford California
United States Travere Investigational Site Tacoma Washington
United States Travere Investigational Site Winter Park Florida
United States Travere Investigational Site Worcester Massachusetts

Sponsors (1)

Lead Sponsor Collaborator
Travere Therapeutics, Inc.

Countries where clinical trial is conducted

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

Outcome

Type Measure Description Time frame Safety issue
Primary Urine protein/creatinine ratio (UP/C) at Week 36 The primary efficacy endpoint is the change from baseline (Day 1) in the UP/C based on a 24-hour urine sample at Week 36. After the last patient randomized has undergone the Week 36 visit
Secondary eGFR over a 52-week period The rate of change in estimated glomerular filtration rate (eGFR) over a 52-week period following the initial acute effect of randomized therapy (the initial acute effect of randomized therapy is defined as the first 6 weeks of randomized treatment with study medication; thus, the analysis is from 6 weeks postrandomization to 58 weeks postrandomization eGFR chronic slope at 1 year.) Week 58 postrandomization
Secondary eGFR over a 104-week period The rate of change in estimated glomerular filtration rate (eGFR) over a 104-week period following initial acute effect of randomized therapy (the initial acute effect of randomized therapy is defined as the first 6 weeks of randomized treatment with study medication; thus, the analysis is from 6 weeks postrandomization to 110 weeks postrandomization eGFR chronic slope at 2 years.) Week 110 postrandomization
Secondary eGFR over a 110-week period The rate of change in eGFR over a 110-week (approximately 2 years) period following the initiation of randomized therapy (thus, the analysis is from Day 1 to 110 weeks postrandomization eGFR total slope at 2 years). Week 110 postrandomization
See also
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Recruiting NCT05856760 - A Study to Investigate Safety and Effect of Sparsentan in Combination With SGLT2 Inhibition in Participants With IgAN Phase 2
Recruiting NCT04662723 - Multicentre Clinical Study to Evaluate the Effect of Personalized Therapy on Patients With Immunoglobulin A Nephropathy. Phase 4
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Completed NCT04287985 - Safety and Efficacy Study of VIS649 for IgA Nephropathy Phase 2
Recruiting NCT05097989 - Study of ALXN2050 in Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN) Phase 2
Completed NCT05200871 - Humanistic Burden of (FSGS) Focal Segmental Glomerulosclerosis and IgAN (Immunoglobulin A Nephropathy)
Terminated NCT05162066 - Study to Evaluate the Safety, Tolerability of BCX9930 in Participants With Either Complement 3 Glomerulopathy (C3G), Immunoglobulin A Nephropathy (IgAN), or Primary Membranous Nephropathy (PMN) Phase 2
Active, not recruiting NCT04573920 - Atrasentan in Patients With Proteinuric Glomerular Diseases Phase 2
Withdrawn NCT02605525 - Efficacy and Safety of SM101 in the Treatment of IgA Nephropathy Phase 2
Recruiting NCT04564339 - Study of Ravulizumab in Proliferative Lupus Nephritis (LN) or Immunoglobulin A Nephropathy (IgAN) Phase 2
Active, not recruiting NCT04573478 - Atrasentan in Patients With IgA Nephropathy Phase 3
Active, not recruiting NCT04663204 - A Study of the Safety and Activity of Sparsentan for the Treatment of Incident Patients With Immunoglobulin A Nephropathy Phase 2

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