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

Phase 1

• Conditions: Focal segmental glomerulosclerosis (FSGS); MedDRA version: 21.1Level: PTClassification code 10067757Term: Focal segmental glomerulosclerosisSystem Organ Class: 10038359 - Renal and urinary disorders; Therapeutic area: Diseases [C] - Symptoms and general pathology [C23]

• Registration Number: EUCTR2016-005141-23-PT
• Lead Sponsor: Travere Therapeutics Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-04-12
• Last Update Posted: 5 August 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

1. The patient or parent/legal guardian (as appropriate) is willing and able to provide signed informed consent/assent
2. 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. 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. UP/C =1.5 g/g (170 mg/mmol) at screening.
5. eGFR =30 mL/min/1.73 m2 at screening.
6. Mean seated blood pressure =100/60 mmHg and =160/100 mmHg.
7. WOCBP agree to the use of contraception and pregnancy testing as described in the protocol.

Inclusion Criteria for the Open-Label Extension:
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.
2.The patient or parent/legal guardian (as appropriate) is willing and able to provide signed informed consent for participation in the open-label extension.
3.The patient received blinded study medication throughout the duration of the double blind period (ie, did not permanently discontinue study medication).

Are the trial subjects under 18? yes
Number of subjects for this age range: 60
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion Criteria

1. FSGS secondary to another condition.
2. Positive findings on serological tests of another primary or secondary glomerular disease.
3. 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. Any organ transplantation, with the exception of corneal transplants.
5. Treatment with any of the prohibited concomitant medications.
6. 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. 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. Clinically significant cerebrovascular disease and/or coronary artery disease.
9. Hemodynamically significant valvular disease.
10. Jaundice, hepatitis, or known hepatobiliary disease (excluding asymptomatic cholelithiasis), or transaminase levels >2 times the upper limit of the normal range at screening.
11. 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. History of malignancy other than adequately treated basal cell or squamous cell skin cancer or cervical carcinoma within the past 2 years.
13. A screening hematocrit value <27% (0.27 L/L) or hemoglobin value <9 g/dL(90 g/L).
14. A screening potassium value of >5.5 mEq/L(5.5 mmol/L).
15. Body mass index (BMI) >40 and there is a causal relationship to the FSGS lesion.
16. History of alcohol or illicit drug use, or excessive alcohol intake (>21 units per week within 2 years of screening)
17. History of serious side effect or allergic response to any AngII antagonist or ERA or hypersensitivity to any of the excipients
18. Female patient is pregnant, breastfeeding, or planning to conceive during the study.
19. Participation in a study of another investigational product within 28 days prior to screening.
20. Prior exposure to sparsentan.
21. Unable to adhere to the requirements of the study, including swallowing the study medication capsules whole.

Exclusion Criteria for the Open-Label Extension:
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 open-label extension.
1.The patient has progressed to ESRD requiring RRT.
2.The patient developed criteria for discontinuation as defined in Section 6.4.2 or Section 6.5 between Week 108 and Week 112.
3.The patient was unable to initiate, or developed contraindications to, treatment with RAAS inhibitors between Week 108 and Week 112.
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.
5. The female patient is pregnant, plans to become pregnant during the course of the study, or is breastfeeding.

Study & Design

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