Ignite Creation Date:
2025-12-17 @ 1:44 PM
Ignite Modification Date:
2025-12-23 @ 6:13 PM
Study NCT ID:
NCT01007461
Status:
WITHDRAWN
Last Update Posted:
2017-05-19
First Post:
2009-10-26
Is Possible Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
IK-1001 (Sodium Sulfide (Na2S) for Injection) in Subjects With Acute ST-Segment Elevation Myocardial Infarction
Sponsor:
Mallinckrodt
Organization:
Study Overview
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
Status:
WITHDRAWN
Status Verified Date:
2017-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Company decision. Non-safety related
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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.
Detailed Description:
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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: