A Phase 1b, Randomised, Double-Blind, Parallel Treatment Group Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics of RMC-035 in Subjects Undergoing Non-Emergent On-Pump Coronary Artery Bypass Graft and/or Valve Surgery
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Frequency of Adverse Events (AEs)
研究概览
简要总结
The purpose of the clinical study is to assess safety, tolerability and pharmacokinetics of RMC-035 for the prevention and treatment of acute kidney injury (AKI) in patients undergoing cardiac surgery.
详细描述
This is a study with two parallel treatment groups where subjects are randomized to receive RMC-035 or a matching placebo in a double-blind fashion. The study will comprise of a screening visit, followed by CABG and/or valve replacement on Day 1, double-blind treatment period and a follow-up period up to Day 30.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Female and male subjects with an age ≥18 years
- •Subject is scheduled for non-emergent (elective) CABG and/or valve surgery (single or multiple valves) with use of cardiopulmonary bypass (CPB)
- •Subject has at least ONE of the following risk factors for AKI at screening:
- •History of LVEF <35% for at least 3 months prior to screening assessed by either echocardiography, cardiac MRI or nuclear scan.
- •History of previous open chest cavity cardiac surgery with or without CPB
- •Confirmed diagnosis of type 2 diabetes (T2DM) at least 3 months prior to screening AND ongoing treatment with an approved anti-diabetic drug
- •Age ≥70 years
- •Documented history of heart failure NYHA class II or higher for at least 3 months or longer at screening
- •Documented history of previous AKI before date of screening independent of the etiology of AKI
- •Documented history of anemia with hemoglobin ≤ 11 g/dL (≤6.8 mmol/L) for at least 3 months prior to screening
- •Documented history of albuminuria, defined as UACR >30 mg/g or > 30 mg/24 hour in a 24-hour urine collection.
- •eGFR is ≤ 60 mL/min/1.73 m2 using the Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) equation
排除标准
- •Estimated glomerular filtration rate (eGFR) is <30 mL/min/1.73 m2 using the Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) equation at screening or at baseline
- •Subject has surgery scheduled to be performed without CPB ("off-pump")
- •Subject has surgery scheduled for aortic dissection
- •Subject is scheduled for CABG and/or valve surgery combined with additional non-emergent cardiac surgeries, e.g. for atrial fibrillation ablation
- •Subject is scheduled to undergo trans catheter aortic valve implantation (TAVI) or trans catheter aortic valve replacement (TAVR), or single vessel off-pump surgeries or left ventricular device (LVAD) implantation
- •Subject has a requirement for any of the following within one week prior to surgery: defibrillator or permanent pacemaker, mechanical ventilation, IABP, LVAD, other forms of mechanical circulatory support (MCS) (Note: The prophylactic insertion of an IABP preoperatively for reasons not related to existing LV pump function is not exclusionary)
研究组 & 干预措施
RMC-035
Participants will receive RMC-035 intravenously
干预措施: RMC-035 (Drug)
Placebo
Participants will receive matching placebo solution intravenously
干预措施: Placebo (Drug)
结局指标
主要结局
Frequency of Adverse Events (AEs)
时间窗: Baseline through day 30
* number (%) of subjects with at least one AE * number (%) of subjects with at least one SAE * number (%) of subjects with at least one Treatment-Emergent AE (TEAE) * number (%) of subjects with at least one serious TEAE * number (%) of subjects with at least one non-serious TEAE * number (%) of subjects with at least one TEAE of special interest * number (%) of subjects with at least one TEAEs reported as related (possible/probable) to IMP * number (%) of subjects with at least one TEAEs leading to withdrawal of IMP
Severity of AEs
时间窗: Within 4 days from first dose of IMP
- Number of TEAEs per category (mild, moderate, severe life-threatening, death)
次要结局
- Maximum Observed Concentration (Cmax)(Blood samples taken from pre-dose and up to two hours after start of Dose 5)
- Area Under the Curve (AUC) 0-24h(Blood samples taken from pre-dose and up to two hours after start of Dose 5)
- Elimination Half-life (T1/2)(Blood samples taken from pre-dose and up to two hours after start of Dose 5)