Effectiveness and Safety of Sparsentan as treatment for Primary Focal Segmental Glomerulosclerosis (FSGS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Travere Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

15 Oct 2018 → 19 Mar 2026

Decision date (initial)

2024-09-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Travere Therapeutics Inc.

External identifiers

EU CT number

2023-505494-32-00

EudraCT number

2016-005141-23

ClinicalTrials.gov

NCT03493685

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety, Pharmacokinetic

The efficacy objective of the study is to determine the long-term nephroprotective potential of treatment with sparsentan as compared with an ARB in patients with primary and genetic FSGS. The safety objective of the study is to assess the safety and tolerability of sparsentan by double-blind monitoring of safety endpoints. The open-label objective of the study is to assess the long-term efficacy, safety, and tolerability of open label sparsentan in patients with FSGS.

Secondary objectives 1

1. Not applicable

Conditions and MedDRA coding

Focal segmental glomerulosclerosis (FSGS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Double-Blind Period : The patient or parent/legal guardian (as appropriate) is willing and able to provide signed informed consent/assent
2. Double-Blind Period: Biopsy-proven FSGS lesion(s) or documentation of a genetic mutation in a podocyte protein associated with FSGS. The biopsy may have been performed at any time in the past. The patient will be enrolled based on light microscopy diagnosis of FSGS and supportive findings on either electron microscopy (EM) or immunofluorescence (IF) analysis (preferably both). In exceptional cases, the patient may be enrolled based on light microscopy diagnosis of FSGS lesion(s) in the absence of EM or IF analysis, provided the history and/or the course of the disease are indicative of primary FSGS and the case has been reviewed by the Medical Monitor and Investigator.
3. Double-Blind Period : Male or female aged 18 to 75 years, inclusive weighing at least 20 kg at screening (Note: patients under 18 may be recruited only in the United States and United Kingdom).
4. Double-Blind Period : UP/C ≥1.5 g/g (170 mg/mmol) at screening.
5. Double-Blind Period : eGFR ≥30 mL/min/1.73 m2 at screening.
6. Double-Blind Period : Mean seated blood pressure ≥100/60 mmHg and ≤160/100 mmHg.
7. Double-Blind Period : WOCBP agree to the use of contraception and pregnancy testing as described in the protocol.
8. Open-Label Extension Period:Based on assessments at the Week 108 visit, a patient will meet all of the following criteria to be eligible for the open-label extension. 1.The patient completed participation in the double-blind period, including the Week 112 visit.
9. Open-Label Extension Period: The patient or parent/legal guardian (as appropriate) is willing and able to provide signed informed consent for participation in the open-label extension.
10. Open-Label Extension Period: The patient received blinded study medication throughout the duration of the double blind period (ie, did not permanently discontinue study medication).

Exclusion criteria 26

1. Double-Blind Period: FSGS secondary to another condition.
2. Double-Blind Period: Positive findings on serological tests of another primary or secondary glomerular disease.
3. Double-Blind Period: History of type 1 diabetes mellitus, uncontrolled type 2 diabetes mellitus (hemoglobin A1c [HbA1c] >8%), or nonfasting blood glucose >180 mg/dL (10.0 mmol/L) at screening.
4. Double-Blind Period: Any organ transplantation, with the exception of corneal transplants.
5. Double-Blind Period: Treatment with any of the prohibited concomitant medications.
6. Double-Blind Period: Treatment with rituximab, cyclophosphamide, or abatacept within ≤3 months prior to screening. If a patient is taking other chronic immunosuppressive medications, the dosage must be stable for ≥1 month prior to screening.
7. Double-Blind Period: Documented history of heart failure and/or previous hospitalization for heart failure or unexplained dyspnea, orthopnea, paroxysmal nocturnal dyspnea, ascites, and/or peripheral edema.
8. Double-Blind Period: Clinically significant cerebrovascular disease and/or coronary artery disease.
9. Double-Blind Period: Hemodynamically significant valvular disease.
10. Double-Blind Period: Jaundice, hepatitis, or known hepatobiliary disease (excluding asymptomatic cholelithiasis), or transaminase levels >2 times the upper limit of the normal range at screening.
11. Double-Blind Period: Positive at screening for the human immunodeficiency virus (HIV) or markers indicating acute or chronic hepatitis B virus (HBV) infection or hepatitis C virus (HCV) infection.
12. Double-Blind Period: History of malignancy other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma within the past 2 years.
13. Double-Blind Period: A screening hematocrit value <27% (0.27 L/L) or hemoglobin value <9 g/dL(90 g/L).
14. Double-Blind Period: A screening potassium value of >5.5 mEq/L(5.5 mmol/L).
15. Double-Blind Period: Body mass index (BMI) >40 and there is a causal relationship to the FSGS lesion.
16. Double-Blind Period: History of alcohol or illicit drug use, or excessive alcohol intake (>21 units per week within 2 years of screening)
17. Double-Blind Period: History of serious side effect or allergic response to any AngII antagonist or ERA or hypersensitivity to any of the excipients
18. Double-Blind Period: Female patient is pregnant, breastfeeding, or planning to conceive during the study.
19. Double-Blind Period: Participation in a study of another investigational product within 28 days prior to screening.
20. Double-Blind Period: Prior exposure to sparsentan.
21. Double-Blind Period: Unable to adhere to the requirements of the study, including swallowing the study medication capsules whole.
22. Open-Label Extension Period:Based on assessments at the Week 108 and Week 112 visits, a patient who meets any of the following criteria will be excluded from the openlabel extension. 1.The patient has progressed to ESRD requiring RRT.
23. Open-Label Extension Period: 2.The patient developed criteria for discontinuation as defined in Section 6.4.2 or Section 6.5 between Week 108 and Week 112.
24. Open-Label Extension Period: 3.The patient was unable to initiate, or developed contraindications to, treatment with RAAS inhibitors between Week 108 and Week 112.
25. Open-Label Extension Period: 4.The patient has an eGFR ≤20 mL/min/1.73 m2 at Week 108. NOTE: If, in the Investigator's opinion, the eGFR value at Week 108 is deemed unlikely to be representative of the patient's true status, the Investigator may repeat the eGFR measurement prior to Week 112 through the central laboratory to assess patient eligibility. Patients with an eGFR <30 mL/min/1.73 m2 will require close monitoring of eGFR and serum potassium throughout the open-label extension.
26. Open-Label Extension Period: 5. The female patient is pregnant, plans to become pregnant during the course of the study, or is breastfeeding.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 8

1. Efficacy End points: The primary efficacy endpoint is the slope of eGFR over approximately 2 years of randomized treatment assessed at the final analysis. The surrogate efficacy endpoint is the proportion of patients achieving a target reduction in proteinuria.
2. Safety End points: Descriptive statistics will be used to summarize the safety data.
3. Open-Label Endpoints: Endpoints for the open-label extension include, but are not necessarily limited to : The absolute and percent change from Week 112 in eGFR at each visit
4. Open-Label Endpoints: The percent change from Week 112 in UP/C at each visit
5. Open-Label Endpoints: Changes from Week 112 in QOL at each visit
6. Open-Label Endpoints: Changes from Week 112 in body weight, vital signs, physical examinations, peripheral edema, and clinical laboratory parameters
7. Open-Label Endpoints: Changes from Week 112 in lipid profile (total cholesterol and triglycerides, LDL-C, and HDL C
8. Open-Label Endpoints: The incidence of TEAEs during the open-label extension

Secondary endpoints 1

1. Secondary Efficacy Endpoints: The secondary efficacy endpoints in non-US countries are: • The percent change from Week 6 in eGFR at Week 108 • The percent change in eGFR from baseline of the double-blind period to 4 weeks post -cessation of randomized treatment at Week 112 • The slope of eGFR following the initiation of randomized treatment

Investigational products

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

Test 2

Comparator 1

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 9

Locations

12 EU/EEA countries · 53 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 128 files

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

Application history

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