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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03493685
Other study ID # 021FSGS16010
Secondary ID
Status Active, not recruiting
Phase Phase 3
First received
Last updated
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
Health authority
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

Study Design


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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Recruiting NCT02382874 - Allogenic AD-MSC Transplantation in Idiopathic Nephrotic Syndrome (Focal Segmental Glomerulosclerosis) Phase 1
Completed NCT00464321 - Safety Study of GC1008 in Patients With Focal Segmental Glomerulosclerosis (FSGS) of Single Doses of GC1008 in Patients With Treatment Resistant Idiopathic FSGS Phase 1
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