Clinical trial NCT03493685: Study of Sparsentan in Patients With Primary Focal Segmental Glomerulosclerosis (FSGS)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Focal Segmental Glomerulosclerosis
Lead sponsor: Travere Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2018-04-10
Enrollment: 371
Sex: ALL
Minimum age (years): 8
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Slope of Estimated Glomerular Filtration Rate (eGFR)
timeFrame: From Day 1 to Week 108
measure: Percentage of Participants Achieving FSGS Partial Remission Endpoint (FPRE)
timeFrame: Week 36
Secondary outcomes:
measure: Slope of eGFR Following the Initial Acute Effect of Randomized Treatment
timeFrame: From Week 6 to Week 108
measure: Change From Baseline in eGFR to 4 Weeks Post-cessation of Randomized Treatment
timeFrame: Baseline (Day 1) to Week 112
Other outcomes:
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city: Detroit
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city: Rochester
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city: Wauwatosa
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country: Argentina
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city: New Lambton Heights
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facility: Travere Investigational Site
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city: Seoul
country: Korea, Republic of
facility: Travere Investigational Site
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country: New Zealand
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city: Hamilton
country: New Zealand
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city: Olsztyn
country: Poland
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city: Olsztyn
country: Poland
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city: Piotrków Trybunalski
country: Poland
facility: Travere Investigational Site
city: Warsaw
country: Poland
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country: Poland
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city: Wrocław
country: Poland
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city: Łódź
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facility: Travere Investigational Site
city: Amadora
country: Portugal
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city: Carnaxide
country: Portugal
facility: Travere Investigational Site
city: Lisboa
country: Portugal
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city: Lisbon
country: Portugal
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city: Loures
country: Portugal
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country: Portugal
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city: Setúbal
country: Portugal
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city: Vila Nova De Gaia
country: Portugal
facility: Travere Investigational Site
city: Palma De Mallorca
country: Spain
facility: Travere Investigational Site
state: Baleares
city: Lugo
country: Spain
facility: Travere Investigational Site
state: Burela
city: Sagunto
country: Spain
facility: Travere Investigational Site
state: Valencia
city: Badalona
country: Spain
facility: Travere Investigational Site
city: Barcelona
country: Spain
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city: Barcelona
country: Spain
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city: Barcelona
country: Spain
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city: Barcelona
country: Spain
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city: Ciudad Real
country: Spain
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city: Córdoba
country: Spain
facility: Travere Investigational Site
city: Madrid
country: Spain
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city: Madrid
country: Spain
facility: Travere Investigational Site
city: Majadahonda
country: Spain
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city: Málaga
country: Spain
facility: Travere Investigational Site
city: Santiago De Compostela
country: Spain
facility: Travere Investigational Site
city: Sevilla
country: Spain
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city: Sevilla
country: Spain
facility: Travere Investigational Site
city: Valencia
country: Spain
facility: Travere Investigational Site
city: Valencia
country: Spain
facility: Travere Investigational Site
city: Zaragoza
country: Spain
facility: Travere Investigational Site
city: Solna
country: Sweden
facility: Travere Investigational Site
city: Uppsala
country: Sweden
facility: Travere Investigational Site
city: Uppsala
country: Sweden
facility: Travere Investigational Site
city: Hualien City
country: Taiwan
facility: Travere Investigational Site
city: Kaohsiung City
country: Taiwan
facility: Travere Investigational Site
city: New Taipei City
country: Taiwan
facility: Travere Investigational Site
city: Taichung
country: Taiwan
facility: Travere Investigational Site
city: Taichung
country: Taiwan
facility: Travere Investigational Site
city: Tainan City
country: Taiwan
facility: Travere Investigational Site
city: Taipei City
country: Taiwan
facility: Travere Investigational Site
city: Taipei City
country: Taiwan
facility: Travere Investigational Site
city: Taipei
country: Taiwan
facility: Travere Investigational Site
city: Taoyuan
country: Taiwan
facility: Travere Investigational Site
city: Carshalton
country: United Kingdom
facility: Travere Investigational Site
state: London
city: Whitechapel
country: United Kingdom
facility: Travere Investigational Site
state: London
city: Fulwood
country: United Kingdom
facility: Travere Investigational Site
state: Preston
city: Brighton
country: United Kingdom
facility: Travere Investigational Site
city: Cambridge
country: United Kingdom
facility: Travere Investigational Site
city: Cardiff
country: United Kingdom
facility: Travere Investigational Site
city: Leicester
country: United Kingdom
facility: Travere Investigational Site
city: London
country: United Kingdom
facility: Travere Investigational Site
city: London
country: United Kingdom
facility: Travere Investigational Site
city: Manchester
country: United Kingdom
facility: Travere Investigational Site
city: Newcastle
country: United Kingdom
facility: Travere Investigational Site
city: Reading
country: United Kingdom
facility: Travere Investigational Site
city: Salford
country: United Kingdom
facility: Travere Investigational Site
city: Swansea
country: United Kingdom
facility: Travere Investigational Site
city: York
country: United Kingdom
facility: Travere Investigational Site
Study officials:
affiliation: Travere Therapeutics, Inc.
name: Radko Komers, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Hodson EM, Sinha A, Cooper TE. Interventions for focal segmental glomerulosclerosis in adults. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD003233. doi: 10.1002/14651858.CD003233.pub3.