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EPPIK


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 (EPPIK)
Therapeutic Area Proteinuria, Glomerular Disease
Principal Investigator Lawrence Milner, MD
Min Age 1 Years
Max Age 18 Years
Gender Female
Contact Vidya Iyer
617-636-0186
viyer1@tuftsmedicalcenter.org
More Information https://clinicaltrials.gov/ct2/show/NCT05003986

Overview

Primary Objectives:

• Evaluate the safety and tolerability of sparsentan oral suspension

• Assess changes in proteinuria after once-daily dosing of sparsentan oral suspension over the 108-week treatment period

 

Secondary Objectives:

• Assess the pharmacokinetics (PK) of sparsentan oral suspension in a pediatric population

• Assess changes in estimated glomerular filtration rate (eGFR) after once-daily dosing of sparsentan oral suspension over the 108-week treatment period

 

Exploratory Objective:

• Assess the palatability and acceptability of sparsentan oral suspension

 

Primary Endpoints:

• Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events (AEs) leading to treatment discontinuation, and adverse events of interest (AEOIs)

• Change from baseline in urine protein/creatinine ratio (UP/C) over the 108-week treatment period

Secondary Endpoints:

• Observed plasma PK concentrations at scheduled timepoints and visits

• Steady-state PK parameters (area under the plasma concentration-time curve during a dosing interval [AUCτ], maximum steady-state plasma drug concentration during a dosage interval [Cmax_ss], and minimum steady-state plasma drug concentration [Cmin_ss]) derived from population PK analysis

• Change from baseline in urine albumin/creatinine ratio (UA/C) over the 108-week treatment period

• Change from baseline in eGFR over the 108-week treatment period

• The proportion of subjects with focal segmental glomerulosclerosis (FSGS) and/or minimal change disease (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

Study Details

Inclusion Criteria

  • 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 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

Exclusion Criteria

  • 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).

Study Requirements

This is a multicenter, open-label, 108-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 FSGS and MCD histological patterns

• Population 2: Subjects with 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 PK evaluations at Day 1 (Baseline), Day 2 (Visit 3), and Week 12.

For each population, subjects will be enrolled in 3 cohorts based on age ranges

Enrollment will initially start in both populations for all subjects aged ≥2 years and who are ≥10 kg at Screening and Day 1. For subjects aged <2 years or <10 kg, the Data Monitoring Committee will recommend enrollment to proceed based on exposure and safety data from subjects already enrolled in the study (Section 6.2.1). The 10 kg limit will be determined as “dry weight” by the Investigator’s judgement based on body weight when the child is free of edema or ascites and taking into account most recent premorbid or remission body weight, preferably as the last weight recorded within 3 months of the onset of the nephrotic syndrome.

After screening, subjects (including the washout subjects) meeting the eligibility criteria will undergo comprehensive baseline evaluations and clinical laboratory tests and will then be randomly assigned in a 1:1:1 ratio to 1 of the 3 PK sampling. The safety and tolerability of sparsentan will be evaluated by AEs, vital signs, physical examinations, clinical laboratory parameters, and 12-lead electrocardiograms.

The safety and tolerability of sparsentan will be evaluated by AEs, vital signs, physical examinations, clinical laboratory parameters, and 12-lead electrocardiograms.

Maximum blood volumes for blood sample collection for all ages will be based on body weight according to World Health Organization (WHO) guidance (WHO blood sample volumes in child health research: review of safe limits (https://www.who.int/bulletin/volumes/89/1/10-080010/en/) unless superseded by local requirements.

Pharmacokinetic assessments will be performed at Day 1 (Baseline), Day 2 (Visit 3), and Week 12 (Visit 9). Periodic safety and efficacy assessments will be performed according to the schedules. Adverse events and concomitant medications/therapies will be monitored and recorded from the time of informed consent/assent through study completion

Number of Subjects (Planned):

Approximately 57 pediatric subjects will be enrolled in this study, with approximately 30 subjects in Population 1 and 27 subjects in Population 2