A Randomized, Multicenter, Double-blind, Parallel-group, Active-control Study of the Efficacy and Safety of Sparsentan for the Treatment of Immunoglobulin A Nephropathy (PROTECT)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 162
- 试验地点
- 54
- 主要终点
- Efficacy End points: The primary efficacy endpoint is the change from baseline in the urine protein/creatinine ratio (UP/C) at Week 36.
研究概览
简要总结
The efficacy objective of the study is to determine the effect of sparsentan on proteinuria and preservation of renal function, as compared to an angiotensin receptor blocker (ARB), in patients with immunoglobulin A nephropathy (IgAN). 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 treatment with sparsentan in patients with IgAN.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Double-Blind Period: Male or female, aged ≥18 years.
- •Open-Label Extension Period: The patient did not permanently discontinue study medication during the double-blind period.
- •Open-Label Extension Period: WOCBP, beginning at menarche, must agree to the use of 1 highly reliable (ie, can achieve a failure rate of <1% per year) method of contraception from 7 days prior to the first dose of study medication until 90 days after the last dose of study medication (including open-label sparsentan). One additional barrier method must also be used during sexual activity, such as a diaphragm or diaphragm with spermicide (preferred), or male partner's use of male condom or male condom with spermicide (preferred), from the Week 114 visit until 90 days after the last dose of study medication.
- •Sparsentan + SGLT2 Inhibitor Sub-study: Based on assessments at a regularly scheduled open-label extension visit, a patient must meet all of the following criteria to be eligible for the Sub-study: The patient is participating in the open-label extension and is willing and able to provide signed informed consent for participation in the open-label extension period Sub-study.
- •Sparsentan + SGLT2 Inhibitor Sub-study: The patient has a urine protein excretion value of ≥0.3 g/day.
- •Sparsentan + SGLT2 Inhibitor Sub-study: The patient has an eGFR of ≥25 mL/min/1.73m
- •Sparsentan + SGLT2 Inhibitor Sub-study: The patient is on a stable dose of sparsentan for ≥8 weeks in the open-label extension period that is the maximum tolerated dose.
- •Sparsentan + SGLT2 Inhibitor Sub-study: The patient has ≥12 weeks of the study remaining.
- •Sparsentan + SGLT2 Inhibitor Sub-study: The patient fulfils local requirements, recommendations and does not have contraindications for on-label prescription of dapagliflozin.
- •Double-Blind Period: Biopsy-proven IgAN.
- •Double-Blind Period: Urine protein excretion value ≥1.0 g/day at screening.
- •Double-Blind Period: eGFR value of ≥30 mL/min/1.73 m2 at screening.
- •Double-Blind Period: The patient has been on a stable dose of ACEI and/or ARB therapy for at least 12 weeks prior to screening.
- •Double-Blind Period: At screening, systolic blood pressure ≤150 mmHg and diastolic blood pressure ≤100 mmHg.
- •Double-Blind Period: Women of childbearing potential (WOCBP) must agree to the use of two forms of contraception.
- •Open-Label Extension Period: Based on assessments at the Week 110 and Week 114 visit, a patient must meet all of the following criteria to be eligible for the open-label extension period. The patient completed participation in the double-blind period, including the Week 114 visit.
- •Open-Label Extension Period: The patient is willing and able to provide signed informed consent for participation in the open-label extension period.
排除标准
- •Double-Blind Period: IgAN secondary to another condition.
- •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 Volume/Volume) 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: 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.
- •Open-Label Extension Period: Based on assessments at the Week 110 and Week 114 visits, a patient who meets any of the following criteria will be excluded from the open-label extension period: The patient has progressed to end-stage renal disease (ESRD) requiring renal replacement therapy (RRT).
- •Open-Label Extension Period: The patient developed any criteria for discontinuation of study medication or discontinuation from the study, respectively, between Week 110 and Week
- •Open-Label Extension Period: The patient was unable to initiate, or developed contraindications to, treatment with RAAS inhibitors between Week 110 and Week
- •Open-Label Extension Period: The patient has an eGFR value of ≤20 mL/min/1.73 m2 at Week
- •Open-Label Extension Period: The patient has a potassium value of >5.5 mEq/L (5.5 mmol/L).
- •Double-Blind Period: Cellular glomerular crescents present in >25% of glomeruli on renal biopsy within 6 months prior to screening.
- •Open-Label Extension Period: The female patient is pregnant or is breastfeeding.
- •Sparsentan + SGLT2 inhibitor Sub-study: Based on assessments at an open-label extension visit, a patient who meets any of the following criteria will be excluded from participation in the open-label extension period Sub-study: The patient has progressed to ESRD requiring RRT.
- •Sparsentan + SGLT2 inhibitor Sub-study: The patient has initiated or changed dose of a systemic immunosuppressive medication (including systemic steroids) within 12 weeks.
- •Sparsentan + SGLT2 inhibitor Sub-study: The patient has been taking an SGLT2 inhibitor within 12 weeks.
- •Sparsentan + SGLT2 inhibitor Sub-study: The patient, in the opinion of the Investigator, is unable to adhere to the requirements of the Sub-study.
- •Double-Blind Period: The patient has a chronic kidney disease in addition to IgAN.
- •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 any systemic immunosuppressive medications (including corticosteroids) for >2 weeks within 3 months 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: Jaundice, hepatitis, or known hepatobiliary disease (excluding asymptomatic cholelithiasis), or transaminase levels >2 times the upper limit of the normal range at screening.
结局指标
主要结局
Efficacy End points: The primary efficacy endpoint is the change from baseline in the urine protein/creatinine ratio (UP/C) at Week 36.
Efficacy End points: The primary efficacy endpoint is the change from baseline in the urine protein/creatinine ratio (UP/C) at Week 36.
Safety End points: Descriptive statistics will be used to summarize the safety data. All safety evaluations will be conducted based on the Safety Analysis Set. Observed data will be listed by patient.
Safety End points: Descriptive statistics will be used to summarize the safety data. All safety evaluations will be conducted based on the Safety Analysis Set. Observed data will be listed by patient.
Open-Label Extension Period: Endpoints for the open-label extension period include, but are not necessarily limited to: The absolute and percent change from Week 114 in eGFR at each visit
Open-Label Extension Period: Endpoints for the open-label extension period include, but are not necessarily limited to: The absolute and percent change from Week 114 in eGFR at each visit
Open-Label Extension Period: The percent change from Week 114 in UP/C at each visit
Open-Label Extension Period: The percent change from Week 114 in UP/C at each visit
Open-Label Extension Period: Changes from Week 114 in QoL at each visit
Open-Label Extension Period: Changes from Week 114 in QoL at each visit
Open-Label Extension Period: Changes from Week 114 in body weight, vital signs, physical examinations, peripheral edema, and clinical laboratory parameters
Open-Label Extension Period: Changes from Week 114 in body weight, vital signs, physical examinations, peripheral edema, and clinical laboratory parameters
Open-Label Extension Period: Changes from Week 114 in lipid profile (total cholesterol and triglycerides, low density lipoprotein C, and high density lipoprotein C)
Open-Label Extension Period: Changes from Week 114 in lipid profile (total cholesterol and triglycerides, low density lipoprotein C, and high density lipoprotein C)
Open-Label Extension Period: The incidence of TEAEs during the open-label extension period
Open-Label Extension Period: The incidence of TEAEs during the open-label extension period
Sparsentan + SGLT2 Inhibitor Sub-study: For the Sub-study, the baseline visit (Day 1) is defined as the visit upon which eligibility is assessed. Safety Endpoints: Safety evaluations include the following: Changes from Sub-study baseline in body weight, vital signs, physical examinations, peripheral edema, and clinical laboratory parameters at each visit.
Sparsentan + SGLT2 Inhibitor Sub-study: For the Sub-study, the baseline visit (Day 1) is defined as the visit upon which eligibility is assessed. Safety Endpoints: Safety evaluations include the following: Changes from Sub-study baseline in body weight, vital signs, physical examinations, peripheral edema, and clinical laboratory parameters at each visit.
Sparsentan + SGLT2 Inhibitor Sub-study: The incidence of TEAEs during the Sub-study period.
Sparsentan + SGLT2 Inhibitor Sub-study: The incidence of TEAEs during the Sub-study period.
Sparsentan + SGLT2 Inhibitor Sub-study: Efficacy Endpoints: Endpoints include, but are not limited to: The mean change from Sub-study baseline in UP/C and UA/C based on a 24-hour urine sample at the next scheduled visit.
Sparsentan + SGLT2 Inhibitor Sub-study: Efficacy Endpoints: Endpoints include, but are not limited to: The mean change from Sub-study baseline in UP/C and UA/C based on a 24-hour urine sample at the next scheduled visit.
Sparsentan + SGLT2 Inhibitor Sub-study: Achievement of urinary protein excretion <0.3 g/day at the next scheduled visit.
Sparsentan + SGLT2 Inhibitor Sub-study: Achievement of urinary protein excretion <0.3 g/day at the next scheduled visit.
Sparsentan + SGLT2 Inhibitor Sub-study: Change in absolute and percent change from Sub-study baseline in eGFR at the next scheduled visit.
Sparsentan + SGLT2 Inhibitor Sub-study: Change in absolute and percent change from Sub-study baseline in eGFR at the next scheduled visit.
次要结局
- Rate of change of eGFR
研究者
Travere Call Center
Scientific
Travere Therapeutics Inc.