Evaluation of Sparsentan in Pediatric Patients with Proteinuric Glomerular Diseases: A Phase 2, Open-Label, Single-Arm Cohort Study
- Trial ID
- 2023-505497-14-00
- Protocol
- RTRX-RE021-201
- Sponsor
- Travere Therapeutics Inc.
Trial statistics
Objectives
The primary objective of this study is to evaluate the **safety** and tolerability of sparsentan oral suspension in pediatric subjects with selected proteinuric glomerular diseases, including focal segmental glomerulosclerosis, minimal change disease, immunoglobulin A nephropathy, immunoglobulin A vasculitis, and Alport syndrome. Additionally, the study aims to assess changes in **proteinuria** after once-daily dosing of sparsentan oral suspension over a period of 108 weeks. These objectives are clinically relevant as they address the potential therapeutic benefits and safety profile of sparsentan in managing proteinuria, a common and significant clinical manifestation in these glomerular diseases.
Secondary objectives include: - Assessing the pharmacokinetics (PK) of sparsentan oral suspension in a pediatric population, which is crucial for understanding the drug's absorption, distribution, metabolism, and excretion in this specific demographic. - Evaluating changes in estimated glomerular filtration rate (eGFR) after once-daily dosing of sparsentan oral suspension over 108 weeks, providing insights into the drug's impact on kidney function. - Assessing the palatability and acceptability of sparsentan oral suspension, which is important for ensuring adherence to the treatment regimen in pediatric patients.
Participants
The clinical trial involves a total of **32 participants** diagnosed with **proteinuric glomerular diseases**, including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), immunoglobulin A nephropathy (IgAN), immunoglobulin A vasculitis (IgAV), and Alport syndrome (AS). The study population comprises both male and female subjects, with an age range from 1 year to less than 18 years at the time of screening. Participants were selected based on specific criteria, including an estimated glomerular filtration rate (eGFR) of at least 30 mL/min/1.73 m² and a mean seated blood pressure within the 5th to 95th percentile for their sex and height. The trial includes individuals with a history of treatment with corticosteroids or other immunosuppressive agents, and those with genetic mutations associated with FSGS or MCD. The study population is considered vulnerable, given the inclusion of minors. Lifestyle factors such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is designed as 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, including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), immunoglobulin A nephropathy (IgAN), immunoglobulin A vasculitis (IgAV), and Alport syndrome (AS). The trial will involve the administration of sparsentan as an oral suspension, with a maximum daily dose of 800 mg, over a period of 108 weeks. The primary objectives are to assess the safety and tolerability of sparsentan and to evaluate changes in proteinuria after once-daily dosing. The trial will also measure secondary endpoints, including plasma pharmacokinetic concentrations and changes in urine albumin/creatinine ratio and estimated glomerular filtration rate (eGFR).
Participants will be involved in the study for a total duration of 108 weeks, with the trial estimated to conclude by March 2026. The study will commence with an inclusion (screening) visit, where eligibility criteria such as age, eGFR, and blood pressure will be assessed. Participants will be required to have a mean seated blood pressure between the 5th and 95th percentile for sex and height, and an eGFR of at least 30 mL/min/1.73 m². The study will include follow-up visits at scheduled intervals to monitor safety, efficacy, and pharmacokinetic parameters. The end-of-study visit will mark the completion of the trial, where final assessments will be conducted.
Participants may be withdrawn from the study if they experience treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), or adverse events leading to treatment discontinuation. Additionally, participants who are unable to tolerate the oral suspension due to its smell, taste, aftertaste, volume, or method of administration may also be discontinued. The trial is not categorized as low intervention and is specifically designed to address the needs of pediatric subjects with rare proteinuric glomerular diseases.
Treatment
The clinical trial involves the administration of **Sparsentan**, an investigational medication formulated as an **oral suspension**. The active substance, sparsentan, is of chemical origin and is developed by Travere Therapeutics, Inc. The pharmaceutical form is specifically designed for pediatric use, and the medication is classified as an orphan drug. The maximum daily dose of sparsentan is 800 mg, with a total maximum dose of 599,200 mg over the course of the study. The treatment period extends up to 108 weeks, with the medication administered once daily via the oral route. The study aims to evaluate the safety, tolerability, and efficacy of sparsentan in pediatric subjects with selected proteinuric glomerular diseases.
In this trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus remains solely on the administration of sparsentan to assess its impact on proteinuria and other relevant clinical outcomes. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the prescribed regimen. The trial is designed as an open-label, single-arm cohort study, allowing for a comprehensive evaluation of the pharmacokinetics and therapeutic potential of sparsentan in the target population.
Efficacy
Efficacy in this clinical trial will be assessed through several primary and secondary endpoints. The primary efficacy endpoint is the change from baseline in the urine protein/creatinine ratio (UP/C) over a period of 108 weeks. This parameter is crucial for evaluating the effect of the treatment on proteinuria, a key indicator of kidney function in patients with proteinuric glomerular diseases.
Secondary efficacy endpoints include the change from baseline in urine albumin/creatinine ratio (UA/C) and estimated glomerular filtration rate (**eGFR**) over the same duration. Additionally, the trial will measure the proportion of subjects achieving complete remission of proteinuria, defined as UP/C <0.3 g/g, and the proportion of subjects with focal segmental glomerulosclerosis (FSGS) and/or minimal change disease (MCD) achieving partial remission, defined as UP/C ≤1.5 g/g and >40% reduction in UP/C. These endpoints will provide a comprehensive assessment of the treatment's impact on disease progression and symptom management.
Data collection will occur at scheduled timepoints throughout the 108-week treatment period, ensuring a robust analysis of the treatment's efficacy. The trial will utilize validated laboratory tests to measure UP/C and UA/C ratios, as well as eGFR, to ensure accuracy and reliability in the assessment of these parameters. The results will be analyzed to determine the treatment's effectiveness in reducing proteinuria and improving kidney function in the pediatric population with selected proteinuric glomerular diseases.
Inclusion and Exclusion Criteria
Inclusion Criteria
- For All Subjects (All Three Populations) - The subject or parent/legal guardian is willing and able to provide signed informed consent/assent, the subject is willing to provide assent before any screening procedures.
- For All Subjects (All Three Populations) - The subject has an eGFR ≥30 mL/min/1.73 m2 at screening.
- For All Subjects (All Three Populations) - The subject has a mean seated blood pressure between the 5th and 95th percentile for sex and height.
- For Population 1 - Male or female ≥1 year at screening to <18 years of age at Day 1.
- For Population 1 - 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.
- For Population 2 - Male or female ≥2 years to <18 years of age at Day 1 (Baseline).
- 2.For Population 2 - Has UP/C ≥0.6 g/g (68 mg/mmol) at screening AND one of the following: • Kidney biopsy-confirmed IgAN, IgAV or AS • Diagnosis of AS by genetic testing (pathogenic X-linked COL4A5 mutation OR autosomal-recessive mutations in both alleles of COL4A3 and/or COL4A4 OR autosomal-dominant COL4A3 and/or COL4A4 and digenic mutations [ie, simultaneous mutations in 2 of the COL4A3, COL4A4, and COL4A5 genes].
- For Population 3- Male or female ≥8 years at screening and <18 years of age at Day 1 (Baseline).
- For Population 3- The subject has UP/C ≥1.0 g/g (113 mg/mmol) at screening AND has kidney biopsy-confirmed IgAN
- For Population 3- Subject weighs ≥40 kg
- For Population 3- The subject has been on ACEI and/or ARB therapy for at least 12 weeks prior to screening.
Exclusion Criteria
- For All Subjects (All Three Populations) 1. Weighs <7.3 kg at screening
- Has clinically significant congenital vascular disease
- Has jaundice, hepatitis, or known hepatobiliary disease, or ALT and/or AST >2 times the UL of normal at screening
- Has a history of malignancy within the past 2 years
- Has a screening hematocrit <27% (0.27 L/L) or a hemoglobin value <9 g/dL (90 g/L)
- Has a screening potassium value >5.5 mEq/L (5.5 mmol/L)
- Has any abnormal clinical laboratory screening values that are considered to be clinically significant
- Has a history of allergy to any Ang II antagonist or ERA, including sparsentan, or has a hypersensitivity to any of the excipients
- Female is pregnant, plans to become pregnant during the course of the study, or is breastfeeding
- Female of childbearing potential who do not agree to use 1 highly reliable method of contraception from 7 days before the first dose of the study medication until 28 days after the last dose of study medication and have a - serum pregnancy test at screening and a - urine pregnancy, with + results confirmed by serum, at every study visit
- 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
- Has FSGS or MCD histological pattern secondary to viral infections, drug toxicities, or malignancies
- The subject has had prior exposure to sparsentan
- The subject or parent/legal guardian is unable to adhere to the requirements of the study
- Has immunoglobulin A (IgA) glomerular deposits not in the context of primary IgAN or IgAV (ie, secondary to another condition
- 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 within 6 months before screening
- Taking chronic immunosuppressive medications and not on a stable dose for ≥1 month before screening
- Requires any of the prohibited concomitant medications
- Has undergone any organ transplantation, with the exception of corneal transplants
- Has a documented history of congenital or acquired heart failure and/or previous hospitalization for heart failure or unexplained dyspnea, orthopnea, paroxysmal nocturnal dyspnea, ascites, and/or peripheral edema
- Has hemodynamically significant cardiac valvular disease
- For Population 3 - The subject is unable to swallow the study medication tablets whole.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Recruiting | 12 Aug 2021 | 5 |
 Italy | Recruiting | 12 Aug 2021 | 8 |
 The Netherlands | Recruiting | 12 Aug 2021 | — |
 Poland | Recruiting | 12 Aug 2021 | 2 |
 Spain | Recruiting | 12 Aug 2021 | 8 |
 Sweden | Recruiting | 12 Aug 2021 | 2 |
| Netherlands | — | — | 2 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Sparsentan_DF3 | Test | TABLET | ORAL USE | 400 | 108 | PRD11161698 |
Sparsentan_DF2 | Test | TABLET | ORAL USE | 400 | 108 | PRD11161697 |
Sparsentan_DF4 | Test | ORAL SUSPENSION | ORAL USE | 800.00 | 108 | PRD11161699 |