A 2-stage study to evaluate single doses of MZ-004 at different dose levels in patients with chronic total occlusions. STAGE 1: Open label Training Stage. STAGE 2: Double-blind, randomized, Placebo-Controlled Stage. The TOSCA-5 Study (Total Occlusion Study in Coronary Arteries-5)
- Conditions
- complete occlusion of a coronary arterycoronary chronic total occlusion10011082
- Registration Number
- NL-OMON41937
- Lead Sponsor
- Matrizyme Pharma Corp.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 25
A patient will be eligible for the study if s/he meets all of the following criteria:
1. Patient has provided signed and dated informed consent in accordance with required regulations.
2. Patient is male or female * 18 years of age.
3. If patient is a female of childbearing potential, patient is willing to utilize contraception from Screening through the duration of the study. Adequate contraceptive measures include oral contraceptives (stable use for 2 or more cycles prior to Screening), intra-uterine device (IUD), Depo-Provera®, Norplant® System Implants, surgical sterilization (bilateral tubal ligation, hysterectomy, partner vasectomy), condom or diaphragm or cervical cap plus either contraceptive sponge, foam or jelly. For the purpose of this Study, women of non-childbearing potential are:
a. Females, regardless of age, with functioning ovaries who have a current documented tubal ligation, or who are surgically sterile (i.e. documented total hysterectomy or bilateral oophorectomy) or
b. Females > 45 years of age who are post-menopausal for greater than 1 year (i.e. last menstrual period > 1 year) at Screening.
4. Patient is willing and able to comply with the protocol requirements during the study and be willing to refrain from any other elective cardiac revascularization procedures for the duration of study participation, unless medically necessary.
5. The patient has a clinically driven, planned PCI of the target CTO, in a major epicardial coronary artery, without planned revascularization of other coronary stenosis/stenoses in major epicardial segments.
6. Target CTO must be * 3 calendar months old by either:
a. Proven Chronicity: Angiographic documentation (conventional or coronary) of the target CTO 3 or more calendar months prior to Screening or
b. Assumed Chronicity: Identification of the target occlusion has occurred in the setting of chronic ischemic heart disease, with no known or suspected acute coronary syndrome (ACS) within 3 months.
7. The patient is receiving a course of optimal anti-ischemic medical therapy (at least 2 anti-anginal agents or the maximum tolerated anti-anginal therapy). Medical therapy should include adequate ventricular rate-limiting medication (i.e. Beta-blocker or calcium antagonist) where appropriate.
*
8. For Stream 1 patients only: The patient has a previous failed PCI, with documentation available to the Investigator and Sponsor, confirming that the failed PCI attempt on the target CTO meets the following criteria:
a. Using anterograde techniques, the operator used at least one Category A guide wire and at least one Category B guide wire during the failed PCI attempt and
b. The operator was unable to establish continuity between the proximal and distal true lumen by advancing any guide wire across the target CTO and
c. The overall fluoroscopy time for the entire procedure during the failed PCI attempt was > 15 minutes.
Category A wires are enhanced tip-load (* 2.5 g) specialized coronary guide wires including Miracle Bros, any Confianza, any Conquest, Abbott Vascular Pilot 150, 200, any Progress, any Cross-it XT, Gaia Second, Gaia Third. Commercially available wires, not listed here, that meet Category A requirements may be permitted upon Sponsor approval.
Category B wires are soft-tip, polymer-jacketed coronary guide wires including Fielder XT, Fielder FC, Pilot 50, Sion Black, Shinobi. Commercially available wires, not
A patient who meets any of the following criteria will not be eligible for the study:;1.Patient has documented chest radiation exposure > 4.0 Gray within 8 weeks of Day 0 (not including any Day 0 procedures). In the absence of Gray dosimetry, patients with > 60 minutes fluoroscopy time within 8 weeks of Day 0 will be excluded. ;2.Patient*s target vessel is a saphenous vein graft occlusion.;3.Patient*s target lesion includes an occluded coronary stent.;4.Patient had ACS < 4 weeks from Screening, attributable to any coronary vessel. ;5.Patient had ACS from 4 weeks to 3 calendar months prior to Screening, attributable to the target CTO. NOTE: If ACS is attributable to a different CTO the patient may still qualify. ;6.Patient has known sensitivity to collagenase.;7.Patient has prior injected collagenase and/or any intra-coronary administration of collagenase.;8.Patient was treated in study CTO-1.;9.Patient has a known sensitivity to contrast dye.;10.Patient has estimated glomerular filtration rate (GFR) is < 30 mL/min, as provided for in the clinical chemistry results available at/for Screening.;11.Patient has any medical condition, which in the judgment of the Investigator and/or Sponsor makes the patient a poor candidate for the investigational procedure.;12.Patient is a pregnant or lactating female (check at Screening and Day 0 before randomization).;13.Patient used any investigational or experimental drug or device within 30 days of Screening.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is to estimate the success percentage of anterograde PCI<br /><br>of the CTO lesion in patients who have been treated with MZ-004 compared to<br /><br>those who are treated with placebo. Additionally, safety and tolerability of<br /><br>the drug will be evaluated. </p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary endpoints are to make a comparison between the successfully<br /><br>treated patients and the non-successfully treated patients within the three<br /><br>treatment options when it comes to:<br /><br>- Fluoroscopy time<br /><br>- Total procedure time<br /><br>- Ability to pass a soft wire through the CTO (True-to-true soft wire pass<br /><br>ability, soft wire passage (2 cm behind the proximal layer of the CTO, either<br /><br>intraluminal or extraluminal) </p><br>