Study of Sparsentan in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS)

Focal Segmental Glomerulosclerosis Clinical Trial

— DUPLEX  

Official title:

A Randomized, Multicenter, Double-blind, Parallel, Active-control Study of the Effects of Sparsentan, a Dual Endothelin Receptor and Angiotensin Receptor Blocker, on Renal Outcomes in Patients With Primary FSGS

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03493685
• Other study ID #: 021FSGS16010
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 17, 2018
• Est. completion date: February 2026

Study information

• Verified date: April 2024
• Source: Travere Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To determine the long-term nephroprotective potential of treatment with sparsentan as compared to an angiotensin receptor blocker in patients with primary and genetic focal segmental glomerulosclerosis (FSGS).

Description:

This is a randomized, multicenter, double-blind, parallel, active-control study. Approximately 300 patients aged 8 to 75 years (inclusive) will be enrolled in the study. The study will be conducted in approximately 300 study centers, globally. The investigational drug (sparsentan) is a dual-acting angiotensin receptor blocker and endothelin receptor antagonist. The active control is irbesartan. Patients who meet eligibility criteria will require washout from renin-angiotensin-aldosterone system (RAAS) blockers, if applicable prior to their first dose of study drug. Patients will be randomly assigned in a 1:1 ratio to receive either sparsentan or active control (irbesartan). After completing the double-blind portion of the study, patients may participate in the open-label extension for treatment with sparsentan if they meet eligibility criteria. 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 371
• Est. completion date: February 2026
• Est. primary completion date: March 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 75 Years

Eligibility

Key Inclusion Criteria for the Double-blind Period:

• Sites within the US and UK: The patient is male or female aged 8 to 75 years, inclusive, weighing =20 kg at screening
• Sites outside the US and UK: The patient is male or female aged 18 to 75 years, inclusive, weighing =20 kg at screening
• Biopsy-proven focal segmental glomerulosclerosis (FSGS) lesion(s) or documentation of a genetic mutation in a podocyte protein associated with FSGS.
• Urine protein/creatinine (UP/C) =1.5 g/g (170 mg/mmol) at screening
• eGFR =30 mL/min/1.73 m2 at screening.
• Women of childbearing potential must agree to the use of one highly reliable method of contraception from 7 days prior to the first dose of study medication until 90 days after the last dose of study medication, plus one additional barrier method during sexual activity

Key Exclusion Criteria for the Double-blind Period:

• FSGS secondary to another condition
• Positive serological tests of another primary or secondary glomerular disease not consistent with a diagnosis of primary or genetic FSGS
• History of type 1 diabetes mellitus, uncontrolled type 2 diabetes mellitus, or nonfasting blood glucose >180 mg/dL (10.0 mmol/L)
• Treated with rituximab, cyclophosphamide, or abatacept within =3 months prior to screening; if taking other chronic immunosuppressive medications, the dosage must be stable prior to screening
• Documented history of heart failure, coronary artery disease, or cerebrovascular disease
• Significant liver disease
• Positive at screening for the human immunodeficiency virus or markers indicating acute or chronic hepatitis B virus infection or hepatitis C infection
• History of malignancy other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma within the past 2 years
• Screening hematocrit value <27% (0.27 L/L) or hemoglobin value <9 g/dL (90 g/L)
• Screening potassium value of >5.5 mEq/L (5.5 mmol/L)
• Extreme obesity (ie, =18 years of age with a body mass index (BMI) >40, or is <18 years of age with a BMI in the 99th percentile plus 5 units at screening, in whom there is a causal relationship between obesity and the development of FSGS
• History of alcohol or illicit drug use disorder
• History of serious side effect or allergic response to any angiotensin II antagonist or endothelin receptor antagonist
• Female patient is pregnant, plans to become pregnant during the course of the study, or is breastfeeding. Key Inclusion Criteria for the Open-label Extension Based on assessments at the Week 108

visit:

• Complete participation in the double-blind period, including the Week 112 visit.
• Patient received blinded study medication through the duration of the double-blind period (ie, did not permanently discontinue study medication) Key Exclusion Criteria for the Open-label Extension Based on Assessments at Week 108 and

112 visits:

• Progression to end-stage renal disease requiring replacement therapy
• The patient developed criteria for discontinuation between Week 108 and Week 112
• The patient was unable to initiate, or developed contraindications to, treatment with RAAS inhibitors between Week 108 and Week 112
• eGFR =20 mL/min/1.73 m2 at Week 108

Related Conditions & MeSH terms

• Focal Segmental Glomerulosclerosis
• Glomerulosclerosis, Focal Segmental

Intervention

Drug:
• sparsentan
Double-blind period: target dose of 800 mg daily; Open-label extension: target dose based on dosage from week 114 daily
• Irbesartan
target dose of 300 mg daily

Locations

Country	Name	City	State
Argentina	Travere Investigational Site	Buenos Aires
Argentina	Travere Investigational Site	Córdoba
Argentina	Travere Investigational Site	Córdoba
Argentina	Travere Investigational Site	Santa Fe
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	Nedlands	Western Australia
Australia	Travere Investigational Site	New Lambton Heights	New South Wales
Australia	Travere Investigational Site	Parkville	Victoria
Australia	Travere Investigational Site	Saint Leonards	New South Wales
Australia	Travere Investigational Site	Wollongong	New South Wales
Australia	Travere Investigational Site	Woolloongabba	Queensland
Belgium	Travere Investigational Site	Leuven
Belgium	Travere Investigational Site	Liège
Belgium	Travere Investigational Site	Roeselare
Brazil	Travere Investigational Site	Botucatu
Brazil	Travere Investigational Site	Itaquera
Brazil	Travere Investigational Site	Passo Fundo
Brazil	Travere Investigational Site	Porto Alegre
Brazil	Travere Investigational Site	Recife
Brazil	Travere Investigational Site	Rio De Janeiro
Brazil	Travere Investigational Site	São Paulo
Brazil	Travere Investigational Site	São Paulo
Canada	Travere Investigational Site	Edmonton	Alberta
Canada	Travere Investigational Site	Greenfield Park	Quebec
Canada	Travere Investigational Site	London	Ontario
Croatia	Travere Investigational Site	Zagreb
Czechia	Travere Investigational Site	Nový Jicín
Czechia	Travere Investigational Site	Praha 10	Praha
Czechia	Travere Investigational Site	Praha 2	Praha
Denmark	Travere Investigational Site	Aarhus	Region Midtjylland
Denmark	Travere Investigational Site	Kolding	Southern Denmark
Estonia	Travere Investigational Site	Tallin
Estonia	Travere Investigational Site	Tartu
France	Travere Investigational Site	Bordeaux
France	Travere Investigational Site	Clermont-Ferrand
France	Travere Investigational Site	Créteil
France	Travere Investigational Site	Grenoble Cedex 9
France	Travere Investigational Site	Marseille
France	Travere Investigational Site	Nice
France	Travere Investigational Site	Paris
France	Travere Investigational Site	Paris
France	Travere Investigational Site	Paris Cedex 15
France	Travere Investigational Site	Saint-Priest-en-Jarez
France	Travere Investigational Site	Toulouse
France	Travere Investigational Site	Valenciennes
Germany	Travere Investigational Site	Aachen
Germany	Travere Investigational Site	Berlin
Germany	Travere Investigational Site	Berlin
Germany	Travere Investigational Site	Düsseldorf	Westfalen
Germany	Travere Investigational Site	Hanover
Germany	Travere Investigational Site	Stuttgart
Germany	Travere Investigational Site	Villingen-Schwenningen
Hong Kong	Travere Investigational Site	Hong Kong
Hong Kong	Travere Investigational Site	Lai Chi Kok
Italy	Travere Investigational Site	Bari
Italy	Travere Investigational Site	Bergamo
Italy	Travere Investigational Site	Bologna
Italy	Travere Investigational Site	Firenze
Italy	Travere Investigational Site	Genova
Italy	Travere Investigational Site	Germaneto
Italy	Travere Investigational Site	Lecco
Italy	Travere Investigational Site	Milano
Italy	Travere Investigational Site	Monza
Italy	Travere Investigational Site	Pavia
Italy	Travere Investigational Site	Roma
Italy	Travere Investigational Site	Verona
Korea, Republic of	Travere Investigational Site	Busan
Korea, Republic of	Travere Investigational Site	Daejeon
Korea, Republic of	Travere Investigational Site	Gyeonggi-do
Korea, Republic of	Travere Investigational Site	Gyeonggi-do
Korea, Republic of	Travere Investigational Site	Seoul
Korea, Republic of	Travere Investigational Site	Seoul
New Zealand	Travere Investigational Site	Auckland
New Zealand	Travere Investigational Site	Hamilton
Poland	Travere Investigational Site	Lódz
Poland	Travere Investigational Site	Olsztyn
Poland	Travere Investigational Site	Olsztyn
Poland	Travere Investigational Site	Piotrków Trybunalski
Poland	Travere Investigational Site	Warsaw
Poland	Travere Investigational Site	Warsaw
Poland	Travere Investigational Site	Wroclaw
Portugal	Travere Investigational Site	Amadora
Portugal	Travere Investigational Site	Carnaxide
Portugal	Travere Investigational Site	Lisboa
Portugal	Travere Investigational Site	Lisbon
Portugal	Travere Investigational Site	Loures
Portugal	Travere Investigational Site	Porto
Portugal	Travere Investigational Site	Setúbal
Portugal	Travere Investigational Site	Vila Nova De Gaia
Spain	Travere Investigational Site	Badalona
Spain	Travere Investigational Site	Barcelona
Spain	Travere Investigational Site	Barcelona
Spain	Travere Investigational Site	Barcelona
Spain	Travere Investigational Site	Barcelona
Spain	Travere Investigational Site	Ciudad Real
Spain	Travere Investigational Site	Córdoba
Spain	Travere Investigational Site	Lugo	Burela
Spain	Travere Investigational Site	Madrid
Spain	Travere Investigational Site	Madrid
Spain	Travere Investigational Site	Majadahonda
Spain	Travere Investigational Site	Málaga
Spain	Travere Investigational Site	Palma De Mallorca	Baleares
Spain	Travere Investigational Site	Sagunto	Valencia
Spain	Travere Investigational Site	Santiago De Compostela
Spain	Travere Investigational Site	Sevilla
Spain	Travere Investigational Site	Sevilla
Spain	Travere Investigational Site	Valencia
Spain	Travere Investigational Site	Valencia
Spain	Travere Investigational Site	Zaragoza
Sweden	Travere Investigational Site	Solna
Sweden	Travere Investigational Site	Uppsala
Sweden	Travere Investigational Site	Uppsala
Taiwan	Travere Investigational Site	Hualien City
Taiwan	Travere Investigational Site	Kaohsiung City
Taiwan	Travere Investigational Site	New Taipei City
Taiwan	Travere Investigational Site	Taichung
Taiwan	Travere Investigational Site	Taichung
Taiwan	Travere Investigational Site	Tainan City
Taiwan	Travere Investigational Site	Taipei
Taiwan	Travere Investigational Site	Taipei City
Taiwan	Travere Investigational Site	Taipei City
Taiwan	Travere Investigational Site	Taoyuan
United Kingdom	Travere Investigational Site	Brighton
United Kingdom	Travere Investigational Site	Cambridge
United Kingdom	Travere Investigational Site	Cardiff
United Kingdom	Travere Investigational Site	Carshalton	London
United Kingdom	Travere Investigational Site	Fulwood	Preston
United Kingdom	Travere Investigational Site	Leicester
United Kingdom	Travere Investigational Site	London
United Kingdom	Travere Investigational Site	London
United Kingdom	Travere Investigational Site	Manchester
United Kingdom	Travere Investigational Site	Newcastle
United Kingdom	Travere Investigational Site	Reading
United Kingdom	Travere Investigational Site	Salford
United Kingdom	Travere Investigational Site	Swansea
United Kingdom	Travere Investigational Site	Whitechapel	London
United Kingdom	Travere Investigational Site	York
United States	Travere Investigational Site	Ann Arbor	Michigan
United States	Travere Investigational Site	Bethlehem	Pennsylvania
United States	Travere Investigational Site	Boston	Massachusetts
United States	Travere Investigational Site	Bronx	New York
United States	Travere Investigational Site	Camp Hill	Pennsylvania
United States	Travere Investigational Site	Chapel Hill	North Carolina
United States	Travere Investigational Site	Chicago	Illinois
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	Corpus Christi	Texas
United States	Travere Investigational Site	Dallas	Texas
United States	Travere Investigational Site	Dallas	Texas
United States	Travere Investigational Site	Dallas	Texas
United States	Travere Investigational Site	Denver	Colorado
United States	Travere Investigational Site	Denver	Colorado
United States	Travere Investigational Site	Detroit	Michigan
United States	Travere Investigational Site	Durham	North Carolina
United States	Travere Investigational Site	El Paso	Texas
United States	Travere Investigational Site	Flushing	New York
United States	Travere Investigational Site	Fort Lauderdale	Florida
United States	Travere Investigational Site	Fort Worth	Texas
United States	Travere Investigational Site	Gainesville	Florida
United States	Travere Investigational Site	Hackensack	New Jersey
United States	Travere Investigational Site	Hampton	Virginia
United States	Travere Investigational Site	Hinsdale	Illinois
United States	Travere Investigational Site	Houston	Texas
United States	Travere Investigational Site	Houston	Texas
United States	Travere Investigational Site	Kansas City	Missouri
United States	Travere Investigational Site	Kansas City	Missouri
United States	Travere Investigational Site	Kansas City	Kansas
United States	Travere Investigational Site	Las Vegas	Nevada
United States	Travere Investigational Site	Lawrenceville	Georgia
United States	Travere Investigational Site	Lewisville	Texas
United States	Travere Investigational Site	Los Angeles	California
United States	Travere Investigational Site	Louisville	Kentucky
United States	Travere Investigational Site	Marshfield	Wisconsin
United States	Travere Investigational Site	Mesa	Arizona
United States	Travere Investigational Site	Miami	Florida
United States	Travere Investigational Site	Miami	Florida
United States	Travere Investigational Site	Miami	Florida
United States	Travere Investigational Site	Middlebury	Connecticut
United States	Travere Investigational Site	Minneapolis	Minnesota
United States	Travere Investigational Site	Minneapolis	Minnesota
United States	Travere Investigational Site	Monroe	Louisiana
United States	Travere Investigational Site	Morgantown	West Virginia
United States	Travere Investigational Site	Nampa	Idaho
United States	Travere Investigational Site	New Hyde Park	New York
United States	Travere Investigational Site	New Orleans	Louisiana
United States	Travere Investigational Site	New York	New York
United States	Travere Investigational Site	New York	New York
United States	Travere Investigational Site	New York	New York
United States	Travere Investigational Site	Northridge	California
United States	Travere Investigational Site	Ocala	Florida
United States	Travere Investigational Site	Oklahoma City	Oklahoma
United States	Travere Investigational Site	Orlando	Florida
United States	Travere Investigational Site	Palo Alto	California
United States	Travere Investigational Site	Philadelphia	Pennsylvania
United States	Travere Investigational Site	Phoenix	Arizona
United States	Travere Investigational Site	Pittsburgh	Pennsylvania
United States	Travere Investigational Site	Port Charlotte	Florida
United States	Travere Investigational Site	Raleigh	North Carolina
United States	Travere Investigational Site	Reno	Nevada
United States	Travere Investigational Site	Rochester	Minnesota
United States	Travere Investigational Site	Roseburg	Oregon
United States	Travere Investigational Site	Saint George	Utah
United States	Travere Investigational Site	Salt Lake City	Utah
United States	Travere Investigational Site	Salt Lake City	Utah
United States	Travere Investigational Site	San Diego	California
United States	Travere Investigational Site	San Dimas	California
United States	Travere Investigational Site	San Francisco	California
United States	Travere Investigational Site	Sherman	Texas
United States	Travere Investigational Site	Shreveport	Louisiana
United States	Travere Investigational Site	Spokane	Washington
United States	Travere Investigational Site	Springfield	Massachusetts
United States	Travere Investigational Site	Temple Terrace	Florida
United States	Travere Investigational Site	Torrance	California
United States	Travere Investigational Site	Upland	Pennsylvania
United States	Travere Investigational Site	Victorville	California
United States	Travere Investigational Site	Washington	District of Columbia
United States	Travere Investigational Site	Wauwatosa	Wisconsin
United States	Travere Investigational Site	Wichita	Kansas
United States	Travere Investigational Site	Wilmington	Delaware
United States	Travere Investigational Site	Winston-Salem	North Carolina
United States	Travere Investigational Site	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Travere Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Croatia,  Czechia,  Denmark,  Estonia,  France,  Germany,  Hong Kong,  Italy,  Korea, Republic of,  New Zealand,  Poland,  Portugal,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Slope of Estimated Glomerular Filtration Rate (eGFR)	The total eGFR slope over 2 years, defined as the slope of eGFR following initiation of randomized treatment (ie, Day 1 to Week 108). Estimates are calculated from a mixed-effects model with treatment, Baseline eGFR, analysis visit, treatment-by-analysis visit, randomization stratification factors as fixed effects, and intercept and slope for each participant as a random effect.	From Day 1 to Week 108
Primary	Percentage of Participants Achieving FSGS Partial Remission Endpoint (FPRE)	Percentage of participants achieving FPRE, defined as urine protein-to-creatinine ratio (UP/C) =1.5 grams/gram (g/g) (170 milligrams per millimoles [mg/mmol]) and a >40% reduction from Baseline was analyzed using a generalized linear model to model probability of achieving FPRE. Missing responses were imputed prior to analysis using multiple imputation. A generalized linear model with appropriate link function was implemented with Baseline log (UP/C), treatment, analysis visit, treatment by analysis visit interaction, and randomization strata as fixed effects. For estimates of probability of achieving FPRE, risk difference, and odds ratio, binomial distribution with logit link was used. For relative risk, Poisson distribution with log link was used. Using Rubin's approach, estimated treatment effects are combined across all imputations to obtain overall estimates for probabilities.	Week 36
Secondary	Slope of eGFR Following the Initial Acute Effect of Randomized Treatment	The chronic eGFR slope over 2 years, defined as the slope of eGFR following the initial acute effect of randomized treatment (ie, Week 6 to Week 108). Estimates were calculated from a mixed-effects model with linear spline (ie, change point at Week 6), which included treatment, Baseline eGFR, time from Baseline (TFB) (weeks), time from change point (TFCP) (weeks), treatment-by-TFB and treatment-by-TFCP interactions, and randomization stratification factors as fixed effects, intercept and slopes as random effects. The slope difference was tested by the null hypothesis that the sum of the treatment-by-TFB and treatment-by-TFCP interactions = 0.	From Week 6 to Week 108
Secondary	Change From Baseline in eGFR to 4 Weeks Post-cessation of Randomized Treatment	The change from Baseline to 4 weeks post-cessation of randomized treatment (Week 112) was analyzed via an analysis of covariance (ANCOVA) model on the natural log(eGFR) with treatment, Baseline eGFR, and randomization strata as fixed effects. Only participants who completed the 108-week treatment period were included. Estimated LS Mean and 95% CI are converted to percentages as follows: [exponential (LS mean change from baseline in natural log(eGFR)) minus 1] multiplied by 100. Baseline (Day 1) was defined as the last non-missing assessment prior to and including the first administration of study medication in the study including unscheduled assessments. Percent change from Baseline was calculated as "[(Post Baseline minus Baseline value)/ Baseline value] multiplied by 100.	Baseline (Day 1) to Week 112

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