A Phase 2, Randomized. Double-Blind, Dose-Escalation, Dose-Expansion, Placebo-Controlled, Multi-Center Study of IK-1001 to Evaluate Safety, Pharmacokinetics , and Proof-of-Concept Efficacy in Subjects With Acute ST-Segment Elevation Myocardial Infarction (STEMI) Undergoing Primary Percutaneous Coronary Intervention
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- Mallinckrodt
- 主要终点
- Creatine Kinase, Muscle and Brain (CK-MB) Troponin T
研究概览
简要总结
Myocardial Infarctions (MI) are commonly known as heart attacks. An ST-Segment Elevation Myocardial Infarction (STEMI) is a more severe type of heart attack. Myocardial Infarctions happen when a coronary artery is partially or fully blocked suddenly by a blood clot, causing damage to at least some of the heart muscle being supplied by that artery. In a STEMI, a blood clot completely blocks the coronary artery. This can result in damage to the heart muscle that is supplied by the affected artery. The purpose of the IK-1001 STEMI Study is to evaluate the safety and effectiveness of an investigational study drug (IK-1001). IK-1001 is being studied to determine if it is safe and if it can reduce the amount of damage caused to the heart from a STEMI. Potential subjects may be eligible if they have been diagnosed with a STEMI and undergo a primary percutaneous coronary intervention (PCI, a procedure where a blocked coronary artery is unblocked during a cardiac catheterization), as well as meet other entry criteria. Up to 446 men and women, aged 18-80, will participate in this study at about 50 medical sites around the world. Study participation will last for about six months. Subjects will receive the study drug through an intravenous catheter over three hours during their PCI procedure. Subjects will be monitored in the hospital for approximately three to four days after the PCI. There are three follow-up visits at one, three and six months after the PCI with the study investigator after discharge from the hospital.
详细描述
This is a Phase 2, randomized, dose-escalation, dose-expansion, double-blind, placebo-controlled, multi-center study that will evaluate safety, PK, and POC efficacy in subjects with acute STEMI undergoing PCI.
The study will be conducted in two parts. Part 1 is the dose escalation portion of the study. A minimum of 24 evaluable subjects will be enrolled into Part 1 to receive either IK-1001 (n = 18) or placebo (n = 6). Each subject will receive a continuous infusion of study drug at one of three dose escalating levels of 0.5, 1.0, or 1.5 mg/kg/hr infusion for 3 hours. At each dose level, 8 subjects will be enrolled (6 will receive IK-1001 and 2 will receive placebo). Placebo will consist of commercially available normal saline (NS) [0.9% sodium chloride (NaCl)].
Treatment with study drug (either IK-1001 or placebo) will be initiated only after informed consent is obtained and STEMI diagnosis is made based on clinical and ECG findings. ECG criteria for STEMI diagnosis include:
- Subjects presenting with ≥ 30 minutes of ischemic chest pain but within 12 hours of symptom onset
- Subjects having persistent ST-segment elevation of ≥ 2 mm in at least 2 contiguous leads in ECG
All subjects who receive study drug and have a successful PCI (defined as subjects in whom Grade 3 reperfusion was achieved) will be followed up for safety and efficacy for up to 6 months post-PCI and study drug infusion. Study samples will be collected from all subjects over the first 4 days following PCI for determination of PK parameters of sulfide in blood and thiosulfate in plasma. In Part 1, subjects who do not undergo a PCI for any reason will have study drug discontinued, will be excluded from the efficacy assessments but will be followed up for safety for 7 days, and will be replaced with a new subject.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Presentation to study hospital or institution with diagnosis of STEMI based on clinical and ECG findings (subject presented with ≥ 30 minutes of ischemic chest pain, within 12 hours of symptom onset, and has persistent ST-segment elevation of ≥ 2 mm ST-segment elevation in at least 2 contiguous leads in the ECG.
- •Age between 18 and 80 years (inclusive)
- •Signed Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form
排除标准
- •Prior MI (as determined by subject history and/or ECG), cardiac surgery, or severe pericardial, congenital, cardiomyopathic, or valvular heart disease
- •Cardiac arrest within the past 28 days
- •Requirement for urgent cardiac surgery
- •Previous CABG surgery or PCI
- •Evidence of moderate or severe CHF (Killip Classes III and IV)
- •Any bradyarrhythmia that is expected to require a pacemaker through Day 4 (range 3 to 5 days), thus preventing the MRI
- •Unable to undergo a MRI (including disallowed metallic implants, unable to tolerate gadolinium contrast media, morbid obesity, or severe claustrophobia)
- •Subjects with past or current renal impairment requiring dialysis
- •Active or recent hemorrhage requiring an invasive procedure for evaluation or transfusion or hemorrhagic stroke within 6 weeks prior to presentation
- •Known or suspected aortic dissection
- •Subjects who have received treatment for asthma within the past 12 months
- •Prior history of pulmonary disease requiring chronic oxygen therapy
- •Females of childbearing potential
- •Body weight > 150 kg or Body Mass Index (BMI) > 40 kg/m2
- •Medical problem likely to preclude completion of the study
- •Use of investigational drugs or devices within 30 days prior to enrollment into the study
- •Any underlying medical or psychiatric condition that, in the opinion of the Investigator, makes the subject an unsuitable candidate for the study
- •Known food allergy to sulfite-containing foods and/or any drug allergies to drugs that contain sulfur
研究组 & 干预措施
IK-1001
IK-1001 Sodium Sulfide (Na2S) for Injection
干预措施: Sodium Sulfide (Na2S) for Injection (Drug)
Placebo
0.9% Sodium Chloride (NaCl)
干预措施: Placebo (Drug)
结局指标
主要结局
Creatine Kinase, Muscle and Brain (CK-MB) Troponin T
时间窗: Days 1 through 4, end of treatment
次要结局
- Vital Signs(Study duration)
- 12-Lead ECG(Study duration)
- Adverse Events(Study Duration)
- Cardiac magnetic resonance imaging (MRI)(Day 4, end of treatment)