A Sequential Phase 2/3, Single-Arm, Open-Label Study in Adults Followed by a Randomized, Placebo-Controlled, Double-Blind, Multicenter Study to Evaluate the Efficacy and Safety of APL2 in Adults and Adolescents With Focal Segmental Glomerulosclerosis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 270
- 试验地点
- 6
- 主要终点
- Phase 2: Evaluate the efficacy of APL2 in terms of change from baseline in log-transformed urine protein to creatinine ratio (uPCR)
研究概览
简要总结
This is a sequential phase 2/3 study to evaluate the efficacy and safety of twice-weekly subcutaneous (SC) infusions of APL2 in patients diagnosed with FSGS. The initial phase 2 portion is a single-arm, open-label study in adults diagnosed with FSGS. Phase 2 will commence prior to randomizing for phase 3. The phase 3 portion of the study is a randomized, placebo-controlled, double-blinded, multicenter study in adults and adolescents diagnosed with FSGS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Phase 2: adults aged ≥18 years
- •Phase 3: adults aged ≥18 years; if and where approved, adolescents (aged 12--17 years) at the time of signing the informed consent and assent form
- •Weight ≥30 kg and ≤100 kg at screening
- •FSGS diagnosis
- •Phase 2: primary, genetic, or undetermined FSGS diagnosed by kidney biopsy
- •Phase 3: primary, genetic, or undetermined FSGS diagnosed by kidney biopsy or by recognized podocyte genetic mutation
- •At least 1.5 g/day of proteinuria on a screening 24-hour urine collection and a uPCR of at least 1.5 g/g in at least 2 FMU samples collected during screening
- •Estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2
- •Stable regimen for FSGS treatment for at least 12 weeks prior to randomization, with no planned or anticipated adjustments or dose changes to the stable treatment regimen
排除标准
- •Previous exposure to APL2
- •Evidence of improving kidney disease in the 8 weeks prior to screening or during the screening period according to available data
- •FSGS secondary to another condition (eg, infectious, diabetic, drug-induced, obesity, prematurity, sickle-cell, vesicoureteral reflux, congenital anomalies of the kidney, and urinary tract)
- •Type 1 or uncontrolled (HbA1C ≥8%) type 2 diabetes mellitus
- •History of kidney transplant
- •Current or prior diagnosis of HIV, hepatitis B, or hepatitis C infection or positive serology or viral load during screening that is indicative of active infection with any of these viruses
- •Hypersensitivity to APL2 or to any of the excipients
- •Significant other kidney disease that would, in the opinion of the investigator, confound interpretation of study results
- •Use of rituximab, belimumab, or any approved or investigational anticomplement therapy within 5 half-lives of that product prior to the screening period
研究组 & 干预措施
Phase 2 - APL2
Sub-cutaneous infusions of APL2 (1080 mg / 20mL) twice weekly
干预措施: APL2 (Drug)
Phase 3 - APL2
Adults: Sub-cutaneous infusions of APL2 (1080 mg / 20mL) twice weekly
Adolescents:
≥50 Kg: Sub-cutaneous infusions of APL2 (1080 mg / 20mL) twice weekly 35 to <50kg: First sub-cutaneous infusion of 648mg (12 mL) followed by 810mg (15 mL) every infusion thereafter (i.e. twice weekly) 30 to <35kg: First & Second sub-cutaneous infusion of 540mg (10mL) followed by 648mg (12 mL) every infusion thereafter (twice weekly)
干预措施: APL2 (Drug)
Phase 3 - Placebo
Subcutaneous infusions of a sterile solution, twice-weekly, and equivalent in volume to the active arm based on participant's age and weight
干预措施: Placebo (Other)
结局指标
主要结局
Phase 2: Evaluate the efficacy of APL2 in terms of change from baseline in log-transformed urine protein to creatinine ratio (uPCR)
时间窗: Baseline to Week 12
Change from Baseline in Log-Transformed uPCR will be based on triplicate first morning urine (FMU)
Phase 3: Change from baseline in log-transformed urine protein to creatinine ratio (uPCR)
时间窗: Baseline to Week 52
Change from baseline in log-transformed uPCR will be based on triplicate first morning urine (FMU)
次要结局
- Phase 2: Evaluate the efficacy of APL2 in terms of change from baseline in log-transformed urine albumin to creatinine ratio (uACR)(Baseline to Week 12)
- Phase 3: Slope of estimated Glomerular Filtration Rate (eGFR)(Baseline to Week 104)
- Phase 3: Change from Baseline in log-transformed urine protein to creatinine ratio (uPCR)(Baseline to Week 104)
- Phase 3: Proportion of participants achieving Complete Remission(Week 104)