Sparsentan Treatment in Pediatric Subjects

What is the Purpose of this Study?

The purpose of this study is to determine the safety and effectiveness of an investigational drug called sparsentan in the treatment of kidney diseases and whether it is safe to use in children who are 1-17 years old. The study focuses on patients with select proteinuric glomerular diseases (focal segmental glomerulosclerosis, minimal change disease, immunoglobulin A nephropathy, immunoglobulin A vasculitis, or Alport syndrome). The main study procedures include taking sparsentan, providing blood samples and electrocardiogram readings, and getting tested for swelling (edema).

Previous studies have shown that sparsentan is effective in reducing protein in the urine. The kidneys filter out waste materials out of the blood; the waste is passed out of the body as urine. When damaged, the glomeruli (parts of the kidney that filter the blood) leak protein and sometimes blood cells into the urine. Having protein in urine for long periods of time may eventually lead to kidney failure.

Eligibility

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.

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.
* 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.
* The subject is male or female ≥2 years at screening and \<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 \[ie, simultaneous mutations in 2 of the COL4A3, COL4A4, and COL4A5 genes\])
* The subject is male or female ≥8 years at screening and \<18 years of age at Day 1 (Baseline).
* The subject has UP/C ≥1.0 g/g (113 mg/mmol) at screening AND has kidney biopsy-confirmed IgAN
* Subject weighs ≥40 kg
* The subject has been on ACEI and/or ARB therapy for at least 12 weeks prior to screening
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.
* For Population 3 - the subject is unable to swallow the study medication tablets whole.

Show less

Where can I participate?

Beverly

More about this Clinical Trial

What is the full name of this clinical trial?

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

Study Details

Disease Type/Condition

Other

Principal Investigator

Kamil, Elaine

Co-Investigators

Dechu Puliyanda, Helen Pizzo

Age Group

Children

Phase

IRB Number

STUDY00001521

ClinicalTrials.gov ID

NCT05003986

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org