Effect on Contrast Induced Acute Kidney Injury of APX-115 in Subjects Undergoing Percutaneous Coronary Intervention A Randomized, Double-blind, Parallel Group, Multicenter, Multi-national Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 218
- 试验地点
- 20
- 主要终点
- Safety endpoints: adverse event
研究概览
简要总结
This phase 2 study is to assess the safety and efficacy of APX-115 active doses in Contrast Induced Acute Kidney Disease compared to placebo following multiple oral dosing in patients with undergoing percutaneous coronary intervention. It is anticipated that approximately 230 patients will be randomized into the study in a 1:1 ratio to 400 mg APX-115 (Isuzinaxib hydrochloride) or placebo arm.
详细描述
Patients with chronic kidney disease undergoing percutaneous coronary intervention deserve careful consideration of various clinical options to minimize the risk of contrast-induced acute kidney injury and to optimize clinical outcomes. Contrast-induced acute kidney injury (CI-AKI) is a leading cause of a hospital-acquired renal failure and has been reported to affect both the mortality and morbidity of patients receiving contrast media. Contrast-induced acute kidney injury is the third leading cause of hospital-acquired acute kidney injury and has been recognized as a serious complication of percutaneous coronary intervention (PCI), which may be associated with increased morbidity and mortality.
APX-115 is a potent small molecule inhibitor of NADPH-oxidase (NOX) isozymes developed by AptaBio Therapeutics, Inc. In-vivo study results suggest that multiple NOX isoforms may contribute to renal injury in CI-AKI model, and pan-NOX inhibition may be a new therapeutic approach for prevention of CI-AKI.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
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
- •Willing and able to provide informed consent.
- •Male or female, of any race or ethnicity, 18 years of age or older, inclusive, on the day of informed consent. Racial and ethnic minorities should be included in the study population to the greatest extent possible.
- •Diagnosed with coronary artery disease.
- •Planned to undergo coronary angiography within 4 weeks of being consented.
- •30 mL/min/1.73m2 ≤ eGFR (Glomerular filtration rate) < 90 mL/min/1.73 m2 confirmed by local or central laboratory.
- •Women of childbearing potential or males willing and able to use at least one protocol-specified method of contraception for the duration of their enrolment.
- •Subject is aware of the investigational nature of this study and willing to comply with protocol treatments, blood tests, and other evaluations listed in the ICF.
排除标准
- •Females who are pregnant or who are planning to become pregnant before the end of planned enrolment or who are breastfeeding.
- •Subjects who are not expected to go through PCI at the discretion of investigator or cardiologist
- •Subjects who have a history of hypersensitivity to contrast media or who cannot be administered contrast media according to investigator's discretion
- •Acute myocardial infarction within 1 month prior to Screening
- •CKD stage 4 and 5 confirmed by eGFR < 30 mL/min/1.73 m2 at Screening.
- •Clinically significant heart disease as determined by the Investigator within 2 months prior to Screening including but not limited to any of following; cardiogenic shock, treatment requiring intra-aortic balloon pump (IABP) support, treatment with extra corporeal membrane oxygenation (ECMO), or NYHA class IV heart failure.
- •Uncontrolled treated/untreated hypertension (defined as systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg, mean of measured 2 times at Screening will be permitted).
- •Known or suspected hypersensitivity to any component of the APX-115 formulation.
- •History of acute kidney injury or renal dialysis within 1 month prior to Screening and/or plan to undergo a renal dialysis during enrolment.
- •Clinically apparent liver disease as determined by the Investigator or moderate or severe hepatic impairment as determined by Child-Pugh score (Class B or C) at Screening.
- •Impaired liver function, defined as alanine aminotransferase (ALT) > 2.5 times UNL and Total bilirubin >1.5 × ULN, unless the subject has known Gilbert's syndrome.
- •Any sign or symptom of acute or chronic infection at Screening.
- •Receipt of any investigational drug within 4 weeks prior to Screening.
- •Confirmed or suspected abuse of alcohol or controlled substances within 1 year prior to Screening.
- •Clinically significant hematology abnormalities; hemoglobin <9 g/dL for females or <10 g/dL for males, absolute neutrophil count <1500/mm3, platelet count <100 × 109/L) at Screening. If any parameter is below the specified threshold, one hematology retest analyzed at the central or local laboratory within a week prior to randomization is permitted with the result of the last sample being conclusive.
- •Any other clinically significant medical condition or laboratory abnormality as determined by the Investigator that might jeopardize the safety of the subject, impair subject compliance, or impede safety/efficacy observations during enrolment.
- •Mental incapacity, unwillingness, or language barrier precluding adequate understanding or cooperation with protocol requirements
- •Use of CYP1A2, CYP2B6 and CYP3A4 substrates or UGT inhibitors and inducers or OAT3 substrates prior to enrollment or concurrently. It will be only accepted to be eligible to screening if the subjects' concomitant medications will be reviewed and approved by the medical monitor and/or sponsor prior to the initial study dose
研究组 & 干预措施
Isuzinaxib (APX-115)
4 x Isuzinaxib 88 mg calculated as free base (4 x 100mg APX-115(Isuzinaxib hydrocloride) capsules as salt form) administered QD, orally, for 5 consecutive days
干预措施: Isuzinaxib (APX-115) (Drug)
Placebo
4 x Placebo capsules administered QD, orally, for 5 consecutive days
干预措施: Placebo (Drug)
结局指标
主要结局
Safety endpoints: adverse event
时间窗: Day -2 to day 84
Number of adverse events
Safety endpoints: labs
时间窗: Day 0 to day 84
Number of abnormal results of Hematology, Biochemistry and Urinalysis
Safety endpoints: vital sign
时间窗: Day 0 to day 84
Number of subjects with abnormal Vital Signs
Safety endpoints: ECG
时间窗: Day 0 to day 84
Abnormal Electrocardiogram (ECG)
Safety endpoints: physical exam
时间窗: Day 0 to day 84
Abnormal physical examination
次要结局
- pharmacokinetics parameters: peak concentration (Cmax, Tmax)(Day -2~2)
- pharmacokinetics parameters: apparent total clearance (CL/F)(Day -2~2)
- Incidence rate of Acute kidney injury(from baseline up to 72 hours after PCI procedure)
- pharmacokinetics parameters: renal clearance (CLR)(Day -2~2)
- pharmacokinetics parameters: apparent nonrenal clearance (CLNR/F)(Day -2~2)
- Kidney function parameters: creatinine, BUN(over 12-week period)
- pharmacokinetics parameters: steady state peak plasma concentration (Css,max)(Day -2~2)
- Long term kidney function: Serum creatinine(week 4 and week 12)
- Long term kidney function: eGFR(week 4 and week 12)
- Kidney function parameters: eGFR(over 12-week period)
- pharmacokinetics parameters: the area under the plasma concentration-time curve (AUC0-last, AUCtau)(Day -2~2)
- pharmacokinetics parameters: steady state trough plasma concentration (Css,min)(Day -2~2)
- pharmacokinetics parameters: apparent volume of distribution (V/F)(Day -2~2)
- pharmacokinetics parameters: fraction/cumulated fraction of excreted in urine(Day -2~2)
- pharmacokinetics parameters: steady state after 5 consecutive days of drug administration(Day -2~2)
- pharmacokinetics parameters: terminal half-life (t1/2)(Day -2~2)