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Study of Sparsentan Treatment in Pediatrics With Proteinuric Glomerular Diseases (EPPIK)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05003986
Recruitment Status : Recruiting
First Posted : August 13, 2021
Last Update Posted : September 26, 2022
Sponsor:
Information provided by (Responsible Party):
Travere Therapeutics, Inc.

Brief Summary:
To evaluate the safety, efficacy and tolerability of sparsentan oral suspension and assess changes in proteinuria after once-daily dosing over the 108-week treatment period.

Condition or disease Intervention/treatment Phase
Focal Segmental Glomerulosclerosis Minimal Change Disease Immunoglobulin A Nephropathy IgA Vasculitis Alport Syndrome Drug: Sparsentan Phase 2

Detailed Description:

This is a multicenter, open-label, 112-week study of sparsentan in approximately 57 pediatric subjects aged ≥1 year to <18 years with selected proteinuric glomerular diseases, divided into 2 populations, defined as follows:

  • Population 1: Subjects with selected proteinuric glomerular diseases associated with Focal Segmental Glomerulosclerosis (FSGS) and Minimal Change Disease (MCD) histological patterns
  • Population 2: Subjects with kidney biopsy-confirmed immunoglobulin A nephropathy (IgAN), immunoglobulin A vasculitis (IgAV), or subjects with Alport syndrome (AS)

The study will evaluate long-term safety, tolerability, and efficacy with pharmacokinetic evaluations at Day 1 (Baseline), Day 2 (Visit 4), and Week 12 (Visit 9). For each population, subjects will be enrolled in 3 cohorts based on age ranges.

Study Enrollment:

  • Population 1: FSGS and/or MCD (30 subjects total)

    1. Cohort 1 (6 subjects): ≥8 years to <18 years
    2. Cohort 2 (18 subjects): ≥3 years to <8 years
    3. Cohort 3 (6 subjects): ≥1 year to <3 years
  • Population 2: IgAN, IgAV, or AS (27 subjects total)

    1. Cohort 1 (9 subjects): ≥8 years to <18 years
    2. Cohort 2 (12 subjects): ≥5 years to <8 years
    3. Cohort 3 (6 subjects): ≥2 years to <5 years

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 57 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label, Single-Arm, Cohort Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Sparsentan Treatment in Pediatric Subjects With Selected Proteinuric Glomerular Diseases
Actual Study Start Date : August 12, 2021
Estimated Primary Completion Date : May 1, 2025
Estimated Study Completion Date : June 1, 2025


Arm Intervention/treatment
Experimental: Population 1: FSGS and/or MCD
Subjects with selected proteinuric glomerular diseases associated with FSGS and MCD histological patterns
Drug: Sparsentan
Population 1: 800 mg Sparsentan
Other Name: RE-021

Experimental: Population 2: IgAN, IgAV, or AS
Subjects with biopsy-confirmed immunoglobulin A nephropathy (IgAN), immunoglobulin A vasculitis (IgAV), or subjects with Alport syndrome (AS)
Drug: Sparsentan
Population 2: 400 mg Sparsentan
Other Name: RE-021




Primary Outcome Measures :
  1. Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), AEs leading to treatment discontinuation, and adverse events of interest (AEOIs) [ Time Frame: After the last patient has undergone the week 108 visit (Visit 15). ]
    The incidence of TEAEs, SAEs, AEs leading to treatment discontinuation, and AEOIs

  2. Urine protein/creatinine ratio (UP/C) at week 108 [ Time Frame: After the last patient has undergone the Week 108 visit (Visit 15) ]
    Change from baseline in UP/C over the 108-week treatment period


Secondary Outcome Measures :
  1. Observed plasma Pharmacokinetic (PK) concentrations [ Time Frame: At scheduled Day 1, Day 2 and Week 12 visits ]
    Observed plasma PK concentrations at scheduled timepoints and visits

  2. Steady-state PK parameters area under the plasma concentration-time curve during a dosing interval ([AUCτ]) [ Time Frame: Week 108 ]
    Steady-state PK parameters [AUCτ]

  3. Steady-state PK parameters [Cmax_ss] [ Time Frame: Week 108 ]
    Maximum steady-state plasma drug concentration during a dosage interval [Cmax_ss]

  4. Steady-state PK parameters [Cmin_ss] [ Time Frame: Week 108 ]
    Minimum steady-state plasma drug concentration [Cmin_ss] derived from population PK analysis

  5. Urine albumin/creatinine ratio (UA/C) over the 112 weeks [ Time Frame: Week 112 ]
    Change from baseline in UA/C through the end of the study (i.e. at Week 112)

  6. Urine protein/creatinine ratio (UP/C) over the 112 weeks [ Time Frame: Week 112 ]
    Change from baseline in UP/C through the end of the study (i.e. at Week 112)

  7. Estimated glomerular filtration rate (eGFR) over the 112 weeks [ Time Frame: Week 112 ]
    Change from baseline in eGFR through the end of the study (i.e. at Week 112)

  8. Proportion of subjects with FSGS and/or MCD histological patterns achieving partial remission [ Time Frame: Week 108 ]
    The proportion of subjects with FSGS and/or MCD histological patterns achieving partial remission defined as UP/C ≤1.5 g/g and >40% reduction in UP/C over the 108-week treatment period



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria for All Subjects (Both Populations):

A subject must meet all of the following criteria to be eligible for participation in this study:

  • The subject or parent/legal guardian (as appropriate) is willing and able to provide signed informed consent/assent, and where required, the subject is willing to provide assent before any screening procedures per local requirements.
  • The subject has an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 at screening.
  • The subject has a mean seated blood pressure between the 5th and 95th percentile for sex and height.

Inclusion Criteria for Population 1:

  • The subject is male or female ≥1 year at screening and <18 years of age at Day 1 (Baseline).
  • The subject has a UP/C ≥1.5 g/g (170 mg/mmol) at screening AND one of the following:
  • Kidney biopsy-proven FSGS or MCD histological patterns and clinical presentation consistent with primary FSGS or MCD and qualifying proteinuria at screening despite history or ongoing treatment with corticosteroids and/or other immunosuppressive disease-modifying agents.
  • Documentation of a genetic mutation in a podocyte protein associated with FSGS or MCD. Subjects with a documented podocytic mutation do not require kidney biopsy.
  • Kidney biopsy-proven FSGS histological pattern with medical history and clinical presentation consistent with maladaptive cause of the lesion.

Note: The kidney biopsy may have been performed at any time in the past but must include light microscopy and electron microscopy characteristics and/or immunofluorescence findings consistent with FSGS or MCD.

Inclusion Criteria for Population 2:

  • The subject is male or female ≥2 years to <18 years of age at Day 1 (Baseline).
  • The subject has UP/C ≥0.6 g/g (68 mg/mmol) at screening AND one of the following diagnoses:
  • Kidney biopsy-confirmed IgAN, IgAV, or AS
  • Diagnosis of AS by genetic testing (pathogenic X-linked Collagen, Type IV, Alpha-5 (COL4A5) mutation OR autosomal-recessive mutations in both alleles of Collagen, Type IV, Alpha-3 (COL4A3) and/or Collagen, Type IV, Alpha-4 (COL4A4) OR autosomal-dominant COL4A3 and/or COL4A4 and digenic mutations [ie, simultaneous mutations in 2 of the COL4A3, COL4A4, and COL4A5 genes])

Exclusion Criteria for All Subjects (Both Populations):

A subject who meets any of the following will be excluded from this study:

  • The subject weighs <7.3 kg at screening.
  • The subject has FSGS or MCD histological pattern secondary to viral infections, drug toxicities, or malignancies.
  • The subject has immunoglobulin A (IgA) glomerular deposits not in the context of primary IgAN or IgAV (ie, secondary to another condition; eg, systemic lupus erythematosus and liver cirrhosis).
  • The subject has had an acute onset or presentation of glomerular disease or a diagnostic biopsy or a relapse of glomerular disease requiring new or different class of immunosuppressive treatment (including, but not limited to, systemic corticosteroids, calcineurin inhibitors and mycophenolate mofetil, abatacept, cyclophosphamide, rituximab, ofatumumab, and ocrelizumab) within 6 months before screening.
  • Subjects taking chronic immunosuppressive medications (including systemic steroids) not on a stable dose for ≥1 month before screening.
  • The subject requires any of the prohibited concomitant medications as defined in the study protocol.
  • The subject has undergone any organ transplantation, with the exception of corneal transplants.
  • The subject has a documented history of congenital or acquired heart failure (modified Ross heart failure classification for children Class II to Class IV) and/or previous hospitalization for heart failure or unexplained dyspnea, orthopnea, paroxysmal nocturnal dyspnea, ascites, and/or peripheral edema.
  • The subject has hemodynamically significant cardiac valvular disease.
  • The subject has clinically significant congenital vascular disease.
  • The subject has jaundice, hepatitis, or known hepatobiliary disease, or alanine aminotransferase and/or aspartate aminotransferase >2 times the upper limit of the normal range at screening.
  • The subject has a history of malignancy within the past 2 years.
  • The subject has a screening hematocrit <27% (0.27 L/L) or a hemoglobin value <9 g/dL (90 g/L).
  • The subject has a screening potassium value >5.5 milliequivalent (mEq)/L (5.5 mmol/L).
  • The subject has any abnormal clinical laboratory screening values that are considered by the Investigator to be clinically significant.
  • The subject has a history of allergic response to any angiotensin II antagonist or endothelin receptor antagonist, including sparsentan, or has a hypersensitivity to any of the excipients in the study medication.
  • The female subject is pregnant, plans to become pregnant during the course of the study, or is breastfeeding.
  • Female subjects of childbearing potential, beginning at menarche, who do not agree to use 1 highly reliable (ie, can achieve a failure rate of <1% per year) method of contraception from 7 days before the first dose of the study medication until 28 days after the last dose of study medication. Examples of highly reliable contraception methods include stable oral, implanted, transdermal, or injected contraceptive hormones associated with the inhibition of ovulation or an intrauterine device. One additional barrier method must also be used during vaginal sexual activity, such as a diaphragm, diaphragm with spermicide (preferred), or male partner's use of male condom or male condom with spermicide (preferred), from Day 1/Randomization until 28 days after the last dose of study medication. Female subjects of childbearing potential are defined as those who are fertile after menarche, unless permanently sterile; permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. All female subjects of childbearing potential must have a negative serum pregnancy test result at screening (Visit 1) and a negative urine pregnancy test result, with positive results confirmed by serum, at every study visit from Day 1 (Visit 3) and after.

Note: Before menarche, pregnancy testing and contraceptive use are not required. However, subjects and their parents/legal guardians must be advised that, immediately upon menarche, subjects will be required to begin pregnancy testing and initiate contraceptive use. This requirement cannot be waived.

  • The subject has participated in a study of another study medication within 28 days before screening or plans to participate in such a study during the course of this study.
  • The subject has had prior exposure to sparsentan.
  • The subject or parent/legal guardian (as appropriate), in the opinion of the Investigator, are unable to adhere to the requirements of the study including but not limited to, a history of noncompliance and/or any other reason that causes the Investigator to believe the subject would not be a good candidate for the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05003986


Contacts
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Contact: Travere Call Center 1-877-659-5518 medinfo@travere.com

Locations
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United States, Delaware
Travere Investigational Site Recruiting
Wilmington, Delaware, United States, 19803
United States, Florida
Travere Investigational Site Recruiting
Miami, Florida, United States, 33136
Travere Investigational Site Recruiting
Miami, Florida, United States, 33155
United States, Iowa
Travere Investigational Site Recruiting
Iowa City, Iowa, United States, 52242
United States, Massachusetts
Travere Investigational Site Recruiting
Boston, Massachusetts, United States, 02111
United States, Michigan
Travere Investigational Site Recruiting
Ann Arbor, Michigan, United States, 48109-5008
United States, Minnesota
Travere Investigational Site Recruiting
Minneapolis, Minnesota, United States, 55454
United States, Missouri
Travere Investigational Site Recruiting
Kansas City, Missouri, United States, 64108
United States, New Jersey
Travere Investigational Site Recruiting
Hackensack, New Jersey, United States, 07601
Travere Investigational Site Recruiting
Neptune, New Jersey, United States, 07753
United States, New York
Travere Investigational Site Recruiting
New Hyde Park, New York, United States, 11042
Travere Investigational Site Recruiting
New York, New York, United States, 10016
United States, North Carolina
Travere Investigational Site Recruiting
Chapel Hill, North Carolina, United States, 27514
Travere Investigational Site Recruiting
Charlotte, North Carolina, United States, 28203
Travere Investigational Site Recruiting
Durham, North Carolina, United States, 22710
United States, Ohio
Travere Investigational Site Recruiting
Columbus, Ohio, United States, 43205
United States, Oklahoma
Travere Investigational Site Recruiting
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Travere Investigational Site Recruiting
Philadelphia, Pennsylvania, United States, 19104
Travere Investigational Site Recruiting
Philadelphia, Pennsylvania, United States, 19134
United States, Texas
Travere Investigational Site Recruiting
Houston, Texas, United States, 77030
United States, Washington
Travere Investigational Site Recruiting
Seattle, Washington, United States, 98105
Netherlands
Travere Investigational Site Recruiting
Nijmegen, Netherlands, 6525 GA
Poland
Travere Investigational Site Recruiting
Kraków, Poland, 30-663
Travere Investigational Site Recruiting
Warsaw, Poland, 04-730
Travere Investigational Site Recruiting
Łódź, Poland, 93-338
Spain
Travere Investigational Site Recruiting
Barcelona, Spain, 08035
Travere Investigational Site Recruiting
Madrid, Spain, 28041
Travere Investigational Site Recruiting
Madrid, Spain, 28046
Travere Investigational Site Recruiting
Sevilla, Spain, 41013
Sponsors and Collaborators
Travere Therapeutics, Inc.
Investigators
Layout table for investigator information
Study Director: Radko Komers, MD, PhD Travere Therapeutics, Inc.
Additional Information:
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Responsible Party: Travere Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05003986    
Other Study ID Numbers: RTRX-RE021-201
First Posted: August 13, 2021    Key Record Dates
Last Update Posted: September 26, 2022
Last Verified: September 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Travere Therapeutics, Inc.:
Alport, AS, FSGS, IgAN, IgAV, MCD, pediatrics, peds
Additional relevant MeSH terms:
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Glomerulosclerosis, Focal Segmental
Nephritis, Hereditary
Glomerulonephritis, IGA
Nephrosis, Lipoid
Vasculitis
Kidney Diseases
Urologic Diseases
Vascular Diseases
Cardiovascular Diseases
Glomerulonephritis
Nephritis
Urogenital Abnormalities
Congenital Abnormalities
Collagen Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Nephrosis