Safety, efficacy and pharmacokinetics of sparsentan in pediatric subjects with selected kidney diseases.

Phase 1

• Conditions: Proteinuric glomerular diseases including:•Focal segmental glomerulosclerosis (FSGS) •Minimal change disease (MCD) •Immunoglobulin A nephropathy (IgAN) •Immunoglobulin A vasculitis (IgAV) •Alport syndrome (AS); MedDRA version: 21.1Level: PTClassification code 10067757Term: Focal segmental glomerulosclerosisSystem Organ Class: 10038359 - Renal and urinary disorders; MedDRA version: 20.0Level: PTClassification code 10021263Term: IgA nephropathySystem Organ Class: 10038359 - Renal and urinary disorders; MedDRA version: 22.1Level: LLTClassification code 10082959Term: IgA vasculitisSystem Organ Class: 100000004858; MedDRA version: 20.0Level: PTClassification code 10001843Term: Alport's syndromeSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; MedDRA version: 21.1Level: LLTClassification code 10058326Term: Minimal change diseaseSystem Organ Class: 10038359 - Renal and urinary disorders; Therapeutic area: Diseases [C] - Symptoms and general pathology [C23]

• Registration Number: EUCTR2021-000621-27-ES
• Lead Sponsor: Travere Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-07-27
• Last Update Posted: 18 October 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 57

Inclusion Criteria

For All Subjects (Both Populations)
A subject must meet all of the following criteria to be eligible for participation in this study:
1. 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.
2. The subject has an eGFR =30 mL/min/1.73 m2 at screening.
3. The subject has a mean seated blood pressure between the 5th and 95th percentile for age, sex, and height.

For Population 1
1. The subject is male or female =1 year at screening to <18 years of age at Day 1.
2. The subject has a UP/C =1.5 g/g at screening AND one of the following:
• 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.
• Biopsy-proven FSGS histological pattern with medical history and clinical presentation consistent with maladaptive cause of the lesion.

For Population 2
1. The subject is male or female =2 years to <18 years of age at screening.
2. The subject has UP/C =1.0 g/g at screening AND one of the following:
• Biopsy-confirmed IgAN or IgAV
• AS (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])
Are the trial subjects under 18? yes
Number of subjects for this age range: 57
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

For All Subjects (Both Populations)
A subject who meets any of the following criteria will be excluded from this study:
1. The subject weighs <7.3 kg at screening.
2. The subject has FSGS or MCD histological pattern secondary to viral infections, drug toxicities, or malignancies.
3. 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).
4. 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.
5. Subjects taking chronic immunosuppressive medications (including systemic steroids) not on a stable dose for =1 month before screening.
6. The subject requires any of the prohibited concomitant medications as defined in the study protocol.
7. The subject has undergone any organ transplantation, with the exception of corneal transplants.
8. The subject has a documented history of congenital or acquired heart failure (modified Ross heart failure classification for children Class II to Class IV [Ross 2012]) and/or previous hospitalization for heart failure or unexplained dyspnea, orthopnea, paroxysmal nocturnal dyspnea, ascites, and/or peripheral edema.
9. The subject has hemodynamically significant cardiac valvular disease.
10. The subject has clinically significant congenital vascular disease.
11. 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.
12. The subject has a history of malignancy within the past 2 years.
13. The subject has a screening hematocrit <27% or a hemoglobin value <9 g/dL.
14. The subject has a screening potassium value >5.5 mEq/L.
15. The subject has any abnormal clinical laboratory screening values that are considered by the Investigator to be clinically significant.
16. The subject has a history of allergic response to any Ang II antagonist or ERA, including sparsentan, or has a hypersensitivity to any of the excipients in the investigational product.
17. 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 investigational product until 90 days after the last dose of investigational product. 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 (IUD) in place for at least 3 months. One additional barrier method must also be used during 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 90 days after the last dose of investigational product. 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 oophorect

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified