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
To evaluate the safety, efficacy and tolerability of sparsentan oral suspension and tablets, and assess changes in proteinuria after once-daily dosing over 108 weeks.
⁃ 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