Study of Sparsentan Treatment in Pediatrics With Proteinuric Glomerular Diseases

• Status: Recruiting
• Trial end date: 2025-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Travere Therapeutics, Inc.

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, 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 age, 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.

• The subject has a UP/C ≥1.5 g/g at screening AND one of the following:

• 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.

• Biopsy-proven FSGS histological pattern with medical history and clinical presentation consistent with maladaptive cause of the lesion.

Note: The 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 screening.

• The subject has UP/C ≥1.0 g/g at screening AND one of the following diagnoses:

• Biopsy-confirmed IgAN or IgAV

• AS (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% or a hemoglobin value <9 g/dL.

• The subject has a screening potassium value >5.5 milliequivalent (mEq)/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 investigational product.

• 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 investigational product until 90 days after the last dose of investigational product. 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 in place for at least 3 months. One additional barrier method must also be used during 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 90 days after the last dose of investigational product. 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 investigational product 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.