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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Travere Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]

Trial duration

9 Dec 2021 → ongoing

Decision date (initial)

2024-06-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Travere Therapeutics, Inc.

External identifiers

EU CT number

2023-505497-14-00

EudraCT number

2021-000621-27

ClinicalTrials.gov

NCT05003986

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

1. Evaluate the safety and tolerability of sparsentan oral suspension (Population 1 and Population 2) and tablets (Population 3).

2. Assess changes in proteinuria after once-daily dosing of sparsentan oral suspension and tablets over 108 weeks.

Secondary objectives 3

1. Assess the PK of sparsentan oral suspension and tablets in a pediatric population
2. Assess changes in estimated eGFR after once-daily dosing of sparsentan oral suspension and tablets over 108 weeks
3. Assess the palatability and acceptability of sparsentan oral suspension

Conditions and MedDRA coding

Proteinuric glomerular diseases including: •Focal segmental glomerulosclerosis (FSGS) •Minimal change disease (MCD) •Immunoglobulin A nephropathy (IgAN) •Immunoglobulin A vasculitis (IgAV) •Alport syndrome (AS)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001984-PIP02-20, EMEA-001984-PIP03-20

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. 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.
2. 2. For All Subjects (All Three Populations) - The subject has an eGFR ≥30 mL/min/1.73 m2 at screening.
3. 3. For All Subjects (All Three Populations) - The subject has a mean seated blood pressure between the 5th and 95th percentile for sex and height.
4. 1. For Population 1 - Male or female ≥1 year at screening to <18 years of age at Day 1.
5. 2. 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.
6. 1. For Population 2 - Male or female ≥2 years to <18 years of age at Day 1 (Baseline).
7. 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].
8. 1. For Population 3- Male or female ≥8 years at screening and <18 years of age at Day 1 (Baseline).
9. 2. For Population 3- The subject has UP/C ≥1.0 g/g (113 mg/mmol) at screening AND has kidney biopsy-confirmed IgAN
10. 3. For Population 3- Subject weighs ≥40 kg
11. 4. For Population 3- The subject has been on ACEI and/or ARB therapy for at least 12 weeks prior to screening.

Exclusion criteria 22

1. For All Subjects (All Three Populations) 1. Weighs <7.3 kg at screening
2. Has clinically significant congenital vascular disease
3. Has jaundice, hepatitis, or known hepatobiliary disease, or ALT and/or AST >2 times the UL of normal at screening
4. Has a history of malignancy within the past 2 years
5. Has a screening hematocrit <27% (0.27 L/L) or a hemoglobin value <9 g/dL (90 g/L)
6. Has a screening potassium value >5.5 mEq/L (5.5 mmol/L)
7. Has any abnormal clinical laboratory screening values that are considered to be clinically significant
8. Has a history of allergy to any Ang II antagonist or ERA, including sparsentan, or has a hypersensitivity to any of the excipients
9. Female is pregnant, plans to become pregnant during the course of the study, or is breastfeeding
10. 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
11. 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
12. Has FSGS or MCD histological pattern secondary to viral infections, drug toxicities, or malignancies
13. The subject has had prior exposure to sparsentan
14. The subject or parent/legal guardian is unable to adhere to the requirements of the study
15. Has immunoglobulin A (IgA) glomerular deposits not in the context of primary IgAN or IgAV (ie, secondary to another condition
16. 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
17. Taking chronic immunosuppressive medications and not on a stable dose for ≥1 month before screening
18. Requires any of the prohibited concomitant medications
19. Has undergone any organ transplantation, with the exception of corneal transplants
20. 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
21. Has hemodynamically significant cardiac valvular disease
22. For Population 3 - The subject is unable to swallow the study medication tablets whole.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. The incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events (AEs) leading to treatment discontinuation, and adverse events of interest (AEOIs)
2. Change from baseline in urine protein/creatinine ratio (UP/C) over 108 weeks

Secondary endpoints 6

1. Observed plasma PK concentrations at scheduled timepoints and visits
2. Relevant steady-state PK parameters (area under the plasma concentration-time curve during a dosing interval [AUCτ], maximum steady-state plasma drug concentration [Cmax_ss], and minimum steady-state plasma drug concentration [Cmin_ss])
3. Change from baseline in urine albumin/creatinine ratio (UA/C) and eGFR over 108 weeks
4. The proportion of subjects achieving complete remission of proteinuria, defined as UP/C <0.3 g/g, over 108 weeks
5. 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 108 weeks
6. 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 the oral suspension (Population 1 and Population 2).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Travere Therapeutics Inc.

Sponsor organisation

Travere Therapeutics Inc.

Address

3611 Valley Centre Drive Suite 300

City

San Diego

Postcode

92130-3331

Country

United States

Scientific contact point

Organisation

Travere Therapeutics Inc.

Contact name

Travere Call Center

Public contact point

Organisation

Travere Therapeutics Inc.

Contact name

Travere Call Center

Third parties 12

Locations

6 EU/EEA countries · 17 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 84 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications