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)
- Conditions
- kidney disorders10038430
- Registration Number
- NL-OMON52074
- Lead Sponsor
- Travere Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 2
Inclusion Criteria for All Subjects (All Three 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/assent, 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 sex and height.
Inclusion Criteria for Population 1:
1. The subject is male or female >=1 year at screening and <18 years of age at
Day 1 (Baseline).
2. 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.
Inclusion Criteria for Population 2:
1. The subject is male or female >=2 years at screening and <18 years of age at
Day 1 (Baseline).
2. 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 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])
Inclusion Criteria for Population 3:
1. The subject is male or female >=8 years at screening and <18 years of age at
Day 1 (Baseline).
2. The subject has UP/C >=1.0 g/g (113 mg/mmol) at screening AND has kidney
biopsy confirmed IgAN
3. Subject weighs >=40 kg
4. The subject has been on ACEI and/or ARB therapy for at least 12 weeks prior
to screening.
Subjects diagnosed with IgAN will be assessed for Population 3 (in US and UK
only) after it is determined that enrollment to Population 2 is no longer
possible (ie, enrollment to the applicable population cohort is completed).
Exclusion Criteria for All Subjects (All Three Populations):
A subject who meets any of the following 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)
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% (0.27 L/L) or a hemoglobin
value <9 g/dL (90 g/L).
14. The subject has a screening potassium value >5.5 mEq/L (5.5 mmol/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 angiotensin II
antagonist or endothelin receptor antagonist, including sparsentan, or has a
hypersensitivity to any of the excipients in the study medication.
17. The female subject is pregnant, plans to become pregnant during the course
of the study, or is breastfeeding.
18. 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 study
medication until 28 days after the last dose of study medication. 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. One additional barrier method must also
be used during vaginal sexual activity, such as a diaphragm, diaphragm with
spermicide (preferred), or male partner*s use of male condom or male condom
with spermicide (preferr
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoints:<br /><br>• The incidence of treatment-emergent adverse events (TEAEs), serious adverse<br /><br>events (SAEs), adverse events (AEs) leading to treatment discontinuation, and<br /><br>adverse events of interest (AEOIs)<br /><br>• Change from baseline in urine protein/creatinine ratio (UP/C) over 108 weeks</p><br>
- Secondary Outcome Measures
Name Time Method