ST-Segment Elevation Myocardial Infraction Clinical Trial
Official title:
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
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.
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.
Part 2 of the study will be an expansion of the highest safe continuous infusion dose
evaluated in Part 1. Part 2 aims to further evaluate safety and establish POC efficacy at
this dosing level. Initially, up to 190 eligible subjects will be randomized to receive
either IK-1001 or placebo at a 1:1 ratio. Two interim analyses (IAs) will be done after 64
and 128 subjects complete the MI size evaluation at Day 4 (range 3 to 5 days), respectively.
If there is a safety concern at any dose level, then enrollment in Part 2 will restart at
the next lower safe dosing level determined from Part 1. If there is only an adequate or no
efficacy signal at any dose level, then enrollment in Part 2 may restart at either an
increased dose level (e.g., 1.75 mg/kg/hr for 3 hours) or at a longer duration of infusion
(1.5 mg/kg/hr for 6 hours). A decision to stop the trial for safety, efficacy, or futility
will be assessed at each IA. No more than 446 subjects will be enrolled in Part 2 of the
study.
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