Title of the trial for lay people, in easily understood, i.e. non-technical, language: Testing of MZ-004 (investigational product) at different doses in patients who have a completely blocked coronary artery and comparing the results to a placebo or inactive product.

• Conditions: The use of MZ-004 to facilitate percutaneous coronary intervention in symptomatic patients with a chronic total occlusion who are indicated for revascularization; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2014-004649-28-NL
• Lead Sponsor: Matrizyme Pharma Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-05-26
• Last Update Posted: 7 December 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

Screening Inclusion Criteria
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 and greater than or equal to 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

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 clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To obtain an estimate of the anterograde PCI success rate for patients with a confirmed target CTO in each treatment group and to explore safety and tolerability in these patients.;Secondary Objective: To compare among the 3 treatment groups, between patients with anterograde PCI success and anterograde PCI failure:<br>•Fluoroscopy time<br>•Total procedure time<br>•Soft wire crossing<br>-True-to-true soft wire crossing<br>- Soft wire penetration (2 cm beyond the proximal cap [intraluminal or extraluminal])<br>;Primary end point(s): The following primary endpoint will be used:<br>PCI Success – The proportion of patients in each treatment group (placebo and MZ-004) with improved anterograde PCI success based on the independent blinded angiographic core laboratory assessment<br>;Timepoint(s) of evaluation of this end point: post PCI attempt and after adjudicated angiographic assessment

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Fluoroscopy Time: The time from proximal CTO engagement to either (i) operator-defined successful wire crossing, or (ii) in the absence of successful wire crossing, to procedural abandonment, calculated for each treatment group (MZ-004 vs. placebo), based on the ITT population;<br>•Soft-wire Crossing: The proportion of patients with PCI success using only soft tipped guide wires (tip strength = 1.5 grams, and no use of Miracle Bros, Progress, Confianza, or Pilot 100, 150 or 200 guide wires), calculated for each treatment group (placebo and MZ-004); based on the ITT population;<br>•Total procedural time, defined as the time the lesion is first engaged with the first CTO guide wire until the time of the last coronary angiogram, calculated for each treatment group (placebo and MZ-004);;Timepoint(s) of evaluation of this end point: Post PCI attempt.