Evaluation of Sparsentan Versus Irbesartan on Renal Outcomes in Patients with Primary Focal Segmental Glomerulosclerosis (FSGS)
- Trial ID
- 2023-505494-32-00
- Protocol
- 021FSGS16010
- Sponsor
- Travere Therapeutics Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the long-term **nephroprotective** potential of **sparsentan** compared to an angiotensin receptor blocker (ARB) in patients with primary and genetic **focal segmental glomerulosclerosis (FSGS)**. This is clinically relevant as FSGS is a progressive kidney disorder that can lead to end-stage renal disease, and effective treatments are crucial for improving patient outcomes. Additionally, the study aims to assess the safety and tolerability of sparsentan through double-blind monitoring of safety endpoints. An open-label component will further evaluate the long-term efficacy, safety, and tolerability of sparsentan in FSGS patients. There are no secondary objectives applicable to this study.
Participants
The clinical trial involves a total of **255 participants** diagnosed with **focal segmental glomerulosclerosis (FSGS)**. The study population includes both male and female subjects, aged between 18 to 75 years, with a minimum weight of 20 kg at screening. Participants were selected based on specific criteria, including a biopsy-proven FSGS lesion or documentation of a genetic mutation in a podocyte protein associated with FSGS. The trial population is characterized by a mean seated blood pressure within the range of 100/60 mmHg to 160/100 mmHg and an estimated glomerular filtration rate (eGFR) of at least 30 mL/min/1.73 m² at screening. Lifestyle considerations such as diet and physical activity are not specified. The study includes a vulnerable population, and both genders are represented. Participants are required to provide informed consent, and women of childbearing potential must agree to use contraception and undergo pregnancy testing as per the protocol.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy and safety of **sparsentan** in patients with primary focal segmental glomerulosclerosis (FSGS). This is a randomized, double-blind, parallel, active-control study involving the administration of sparsentan and a comparator, **irbesartan**, both in tablet form for oral use. The trial is structured into a double-blind period followed by an open-label extension. The double-blind period will last approximately 108 weeks, during which participants will receive either sparsentan or irbesartan. The open-label extension will allow all participants to receive sparsentan for an additional period, contingent upon meeting specific criteria at the end of the double-blind phase.
Participants will be required to attend several study visits throughout the trial. The initial visit will be a screening visit to confirm eligibility based on criteria such as age, weight, and specific medical parameters like eGFR and blood pressure. Following successful screening, participants will be randomized to receive either sparsentan or irbesartan. Regular follow-up visits will be scheduled to monitor efficacy and safety endpoints, including changes in eGFR and proteinuria levels. The primary efficacy endpoint is the slope of eGFR over the two-year treatment period, while safety will be assessed through descriptive statistics of adverse events. The end-of-study visit will occur at the conclusion of the open-label extension, where final assessments will be conducted.
The expected duration of participant involvement is approximately 268 weeks, including both the double-blind and open-label phases. Conditions that may lead to early termination from the study include significant adverse events, non-compliance with study procedures, or withdrawal of consent. The trial aims to provide comprehensive data on the long-term nephroprotective potential of sparsentan compared to an angiotensin receptor blocker in patients with FSGS, as well as its safety and tolerability profile.
Treatment
The clinical trial involves the administration of **Sparsentan**, a dual endothelin receptor and angiotensin receptor blocker, as the experimental medication. **Sparsentan** is provided in tablet form and is manufactured by Travere Therapeutics, Inc. The pharmaceutical form is a tablet, and the route of administration is oral. The maximum daily dose of **Sparsentan** is 800 mg, with a total maximum dose of 1,461,600 mg over a treatment period of 268 days. The trial includes two formulations of **Sparsentan**, identified as Sparsentan_DF3 and Sparsentan_DF2, both of which are chemically derived and not formulated for pediatric use. The study aims to evaluate the nephroprotective potential of **Sparsentan** in patients with primary focal segmental glomerulosclerosis (FSGS).
In addition to the experimental treatment, the study employs **Irbesartan** as a comparator treatment. **Irbesartan** is an angiotensin receptor blocker provided in tablet form, with a maximum daily dose of 300 mg and a total maximum dose of 222,600 mg over a treatment period of 108 days. The tablets are over-encapsulated to maintain blinding during the trial. The route of administration for **Irbesartan** is also oral. This comparator treatment is used to assess the efficacy and safety of **Sparsentan** against a standard angiotensin receptor blocker in the management of FSGS.
Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed treatment regimens. The study is designed to provide a comprehensive evaluation of the long-term efficacy, safety, and tolerability of **Sparsentan** compared to **Irbesartan** in the target patient population.
Efficacy
The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary efficacy endpoint is the slope of estimated glomerular filtration rate (**eGFR**) over approximately two years of randomized treatment, which will be evaluated at the final analysis. Additionally, a surrogate efficacy endpoint will be the proportion of patients achieving a target reduction in proteinuria. Secondary efficacy endpoints include the percent change from Week 6 in eGFR at Week 108, the percent change in eGFR from baseline of the double-blind period to four weeks post-cessation of randomized treatment at Week 112, and the slope of eGFR following the initiation of randomized treatment.
For the open-label extension, endpoints will include the absolute and percent change from Week 112 in eGFR at each visit, the percent change from Week 112 in urine protein-to-creatinine ratio (UP/C) at each visit, and changes from Week 112 in quality of life (QOL) at each visit. Additional assessments will include changes from Week 112 in body weight, vital signs, physical examinations, peripheral edema, clinical laboratory parameters, and lipid profile, including total cholesterol, triglycerides, LDL-C, and HDL-C. The incidence of treatment-emergent adverse events (TEAEs) during the open-label extension will also be monitored.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Double-Blind Period : The patient or parent/legal guardian (as appropriate) is willing and able to provide signed informed consent/assent
- 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.
- 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).
- Double-Blind Period : UP/C ≥1.5 g/g (170 mg/mmol) at screening.
- Double-Blind Period : eGFR ≥30 mL/min/1.73 m2 at screening.
- Double-Blind Period : Mean seated blood pressure ≥100/60 mmHg and ≤160/100 mmHg.
- Double-Blind Period : WOCBP agree to the use of contraception and pregnancy testing as described in the protocol.
- 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.
- 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.
- 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
- Double-Blind Period: FSGS secondary to another condition.
- Double-Blind Period: Positive findings on serological tests of another primary or secondary glomerular disease.
- 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.
- Double-Blind Period: Any organ transplantation, with the exception of corneal transplants.
- Double-Blind Period: Treatment with any of the prohibited concomitant medications.
- 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.
- 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.
- Double-Blind Period: Clinically significant cerebrovascular disease and/or coronary artery disease.
- Double-Blind Period: Hemodynamically significant valvular disease.
- 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.
- 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.
- 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.
- Double-Blind Period: A screening hematocrit value <27% (0.27 L/L) or hemoglobin value <9 g/dL(90 g/L).
- Double-Blind Period: A screening potassium value of >5.5 mEq/L(5.5 mmol/L).
- Double-Blind Period: Body mass index (BMI) >40 and there is a causal relationship to the FSGS lesion.
- Double-Blind Period: History of alcohol or illicit drug use, or excessive alcohol intake (>21 units per week within 2 years of screening)
- Double-Blind Period: History of serious side effect or allergic response to any AngII antagonist or ERA or hypersensitivity to any of the excipients
- Double-Blind Period: Female patient is pregnant, breastfeeding, or planning to conceive during the study.
- Double-Blind Period: Participation in a study of another investigational product within 28 days prior to screening.
- Double-Blind Period: Prior exposure to sparsentan.
- Double-Blind Period: Unable to adhere to the requirements of the study, including swallowing the study medication capsules whole.
- 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.
- 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.
- 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.
- 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.
- Open-Label Extension Period: 5. The female patient is pregnant, plans to become pregnant during the course of the study, or is breastfeeding.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 01 Mar 2018 | 5 |
 Croatia | Not Recruiting | 01 Mar 2018 | 6 |
 Czechia | Not Recruiting | 01 Mar 2018 | 7 |
 Denmark | Not Recruiting | 01 Mar 2018 | 2 |
 Estonia | Not Recruiting | 01 Mar 2018 | 1 |
 France | Not Recruiting | 01 Mar 2018 | 14 |
 Germany | Not Recruiting | 01 Mar 2018 | 12 |
 Italy | Not Recruiting | 01 Mar 2018 | 24 |
 Poland | Not Recruiting | 01 Mar 2018 | 6 |
 Portugal | Not Recruiting | 01 Mar 2018 | 6 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Sparsentan_DF2 | Test | TABLET | ORAL USE | 800 | 268 | PRD11161697 |
IRBESARTAN | Comparator | — | ORAL USE | 300 | 108 | SUB08293MIG |
Sparsentan_DF3 | Test | TABLET | ORAL USE | 800 | 268 | PRD11161698 |