A Randomized, Multicenter, Double-blind, Parallel, Active-control Study of the Effects of Sparsentan, a Dual Endothelin Receptor and Angiotensin Receptor Blocker, on Renal Outcomes in Patients with Primary Focal Segmental Glomerulosclerosis (FSGS)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 116
- 试验地点
- 53
- 主要终点
- 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.
研究概览
简要总结
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.
入排标准
- 年龄范围
- 0 years 至 65+ years（65+ Years, 0-17 Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Double-Blind Period : The patient or parent/legal guardian (as appropriate) is willing and able to provide signed informed consent/assent
- •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).
- •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.
排除标准
- •Double-Blind Period: FSGS secondary to another condition.
- •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: Positive findings on serological tests of another primary or secondary glomerular disease.
- •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
- •Open-Label Extension Period: 3.The patient was unable to initiate, or developed contraindications to, treatment with RAAS inhibitors between Week 108 and Week
- •Open-Label Extension Period: 4.The patient has an eGFR ≤20 mL/min/1.73 m2 at Week
- •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:
- •The female patient is pregnant, plans to become pregnant during the course of the study, or is breastfeeding.
- •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.
结局指标
主要结局
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.
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.
Safety End points: Descriptive statistics will be used to summarize the safety data.
Safety End points: Descriptive statistics will be used to summarize the safety data.
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
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
Open-Label Endpoints: The percent change from Week 112 in UP/C at each visit
Open-Label Endpoints: The percent change from Week 112 in UP/C at each visit
Open-Label Endpoints: Changes from Week 112 in QOL at each visit
Open-Label Endpoints: Changes from Week 112 in QOL at each visit
Open-Label Endpoints: Changes from Week 112 in body weight, vital signs, physical examinations, peripheral edema, and clinical laboratory parameters
Open-Label Endpoints: Changes from Week 112 in body weight, vital signs, physical examinations, peripheral edema, and clinical laboratory parameters
Open-Label Endpoints: Changes from Week 112 in lipid profile (total cholesterol and triglycerides, LDL-C, and HDL C
Open-Label Endpoints: Changes from Week 112 in lipid profile (total cholesterol and triglycerides, LDL-C, and HDL C
Open-Label Endpoints: The incidence of TEAEs during the open-label extension
Open-Label Endpoints: The incidence of TEAEs during the open-label extension
次要结局
- 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
研究者
Travere Call Center
Scientific
Travere Therapeutics Inc.