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

Immunoglobulin A Nephropathy Clinical Trial

— PROTECT  

Official title:

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

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
• 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
• 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

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• Immunoglobulin A Nephropathy
• Kidney Diseases

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

External Links

•   Sponsor Website