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Study of Sparsentan Treatment in Pediatrics With Proteinuric Glomerular Diseases

Phase 2
Recruiting
Conditions
IgA Vasculitis
Focal Segmental Glomerulosclerosis
Minimal Change Disease
Immunoglobulin A Nephropathy
Alport Syndrome
Interventions
Registration Number
NCT05003986
Lead Sponsor
Travere Therapeutics, Inc.
Brief Summary

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.

Detailed Description

This is a multicenter, open-label, 112-week study of sparsentan in approximately 67 pediatric subjects aged ≥1 year to \<18 years with selected proteinuric glomerular diseases, divided into 3 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 Alport syndrome (AS)

* Population 3: Subjects with kidney biopsy-confirmed IgAN

The study will evaluate long-term safety, tolerability, and efficacy with pharmacokinetic (PK) evaluations at Day 1 (Baseline), Day 2 (Visit 4), and Week 12 (Visit 9) in Population 1 and Population 2. In Population 3, PK values will be evaluated at Day 1 (Baseline) and at Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, and 96. For Population 1 and Population 2, subjects will be enrolled in 3 cohorts based on age ranges. For Population 3, subjects will be enrolled in one cohort.

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

* Population 3: IgAN (10 subjects total) 1. 10 subjects: ≥8 years to \<18 years

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
67
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Population 1: FSGS and/or MCDSparsentanSubjects with selected proteinuric glomerular diseases associated with FSGS and MCD histological patterns
Population 3: IgANSparsentanSubjects with kidney biopsy-confirmed IgAN
Population 2: IgAN, IgAV, or ASSparsentanSubjects with kidney biopsy-confirmed immunoglobulin A nephropathy (IgAN), immunoglobulin A vasculitis (IgAV), or Alport syndrome (AS)
Primary Outcome Measures
NameTimeMethod
Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), AEs leading to treatment discontinuation, and adverse events of interest (AEOIs)After the last patient has undergone the week 108 visit (Visit 15).

The incidence of TEAEs, SAEs, AEs leading to treatment discontinuation, and AEOIs

Urine protein/creatinine ratio (UP/C) at week 108After the last patient has undergone the Week 108 visit (Visit 15)

Change from baseline in UP/C over 108 weeks

Secondary Outcome Measures
NameTimeMethod
Urine albumin/creatinine ratio (UA/C) over 108 weeksWeek 108

Change from baseline in UA/C over 108 weeks

Estimated glomerular filtration rate (eGFR) over 108 weeksWeek 108

Change from baseline in eGFR over 108 weeks

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

Steady-state PK parameters \[AUCτ\]

Steady-state PK parameters [Cmax_ss]Week 108

Maximum steady-state plasma drug concentration \[Cmax_ss\]

Steady-state PK parameters [Cmin_ss]Week 108

Minimum steady-state plasma drug concentration \[Cmin_ss\]

Observed plasma Pharmacokinetic (PK) concentrationsAt scheduled Day 1, Day 2 and Week 12 visits for Population 1 and 2. At scheduled Day 1 and Week 4, 8, 12, 24, 36, 48, 60, 72, 84, and 96 visits for Population 3.

Observed plasma PK concentrations at scheduled timepoints and visits

Proportion of subjects achieving complete remission of proteinuriaWeek 108

The proportion of subjects achieving complete remission of proteinuria, defined as UP/C \<0.3 g/g over 108 weeks

Proportion of subjects with FSGS and/or MCD histological patterns achieving partial remissionWeek 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 108 weeks

Proportion of subjects who discontinue study medication due to inability to tolerate the oral suspensionWeek 108

The proportion of subjects who discontinue study medication due to inability to tolerate the smell, taste, aftertaste, volume of administration, or method of administration of oral suspension in Population 1 and Population 2

Trial Locations

Locations (1)

Travere Investigational Site

🇬🇧

Manchester, United Kingdom

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