Collagenase Total Occlusion-1 Trial

NCT01271335 | Completed Phase 1 DMC

• 2 other identifiers: CTO-1CIHR
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

A prospective, three-center, phase I safety and tolerability dose escalation study, evaluating 28 subjects in 4 discrete dose cohorts of acute intracoronary injected collagenase ranging from 300 - 1200 µg prior to routine standard-of-care percutaneous revascularization procedures in subjects with chronic total coronary artery occlusions (CTOs).

Conditions

Chronic Total Occlusions

Keywords

CTO; Angioplasty; PCI

Outcome Measures

Primary Outcomes (1)

• Safety

  * Major Adverse Cardiac events, AE and SAE. * Cardiac enzymes, hematology and biochemistry; changes between Screening relative to Days 1 \& 30. * Vital Signs * A 2D-echocardiogram examination will be done on Day1 (18-24 hours after the collagenase administration prior to the CTO crossing procedure) and again on Day2 prior to discharge.

  At 3 months

Secondary Outcomes (2)

• Efficacy

  Day 2

• Pharmacokinetic

  PK blood draws will be assessed at 15, 30, 60, 120, 240, 480 min. and 18 hrs post removal of microcatheter

Study Arms (1)

Collagenase (MZ-004)

EXPERIMENTAL

Local intra-coronary administration of MZ-004 at or into the CTO

Biological: collagenase

Interventions

collagenase BIOLOGICAL

Lyophilized powder / sterile dosage form for single local intravascular administration via the occluded coronary.

Also known as: MZ-004

Collagenase (MZ-004)

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is willing and able to provide an informed consent
• Subject is willing and able to comply with the study procedures and follow-up
• Subject is 35 years of age or older
• Women who are non-reproductive, or reproductive women who are willing and able to practice effective birth control methods. A urine pregnancy test should be done at the screening/Day0 on all reproductive women of child bearing ability
• Subjects with CTO (older than 6 weeks or unknown duration based on the investigator's assessment of appropriateness for the study) with a clinical indication for revascularization. In subjects with occlusions of unknown duration, there must be absence of any identifiable ischemic event in the 6 weeks prior to enrolment in the study
• At least 1 previously failed attempt to cross the CTO
• Absence of pericardial effusion on 2D Echocardiogram

You may not qualify if:

• Candidates for this study who meet any of the following criteria at the time of the screening visit are NOT eligible to be enrolled in this study:
• Culprit vessel is a saphenous vein graft occlusion
• True ostial LAD, LCX or RCA occlusions (since collagenase delivery will be unreliable)
• Presence of moderate or large pericardial effusion on echocardiogram within 2 weeks of the procedure
• Major side branch (1.5 mm diameter) within 3 mm proximal to the occlusion. (This is to prevent the infusate being diverted through a side branch and to prevent ischemia during the prolonged period of time during the infusion)
• Renal dysfunction (creatinine greater than 2 x ULN)
• Severe calcification (collagenase can not degrade calcium) based on consensus of 2 interventional cardiologists after review of coronary angiogram.
• Subject has any medical condition, which in the judgment of the Investigator and/or designee makes the subject a poor candidate for the investigational procedure
• Subject is or has been partaking in another investigational product clinical study within 30 days of Screening/Day0
• Subjects with bleeding abnormalities (e.g. Factor VIII deficiency) and /or subjects that have experienced any medically documented active site of bleeding within 30 days of the screening visit, such as, but not limited to, the gastrointestinal or genitourinary tract or intercerebral hemorrhage.

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead

Study Sites (1)

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Related Publications (1)

• Strauss BH, Osherov AB, Radhakrishnan S, Mancini GB, Manners A, Sparkes JD, Chisholm RJ. Collagenase Total Occlusion-1 (CTO-1) trial: a phase I, dose-escalation, safety study. Circulation. 2012 Jan 24;125(3):522-8. doi: 10.1161/CIRCULATIONAHA.111.063198. Epub 2011 Dec 16.

  PMID: 22179536 DERIVED

MeSH Terms

Interventions

Collagenases

Intervention Hierarchy (Ancestors)

Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases

Study Officials

• Bradley Strauss, MD, PhD, FRCP(C)

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of the Schulich Heart Program, Head of the Division of Cardiology and Reichmann Chair in Cardiovascular Science

Study Record Dates

• First Submitted: January 5, 2011
• First Posted: January 6, 2011
• Study Start: November 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: February 1, 2012
• Last Updated: March 23, 2012

Record last verified: 2012-03

Locations

CA (1)