Safety of PZ-128 in Subjects Undergoing Non-Emergent Percutaneous Coronary Intervention

NCT02561000 | Completed Phase 2 Results DMC

• 2 other identifiers: TMC-PZ128-02P50HL110789
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 3

Brief Summary

The object of the study is to determine whether different doses of PZ-128, when added to standard medical care in persons undergoing cardiac catheterization/percutaneous coronary intervention, will increase the risk of bleeding. A secondary objective is to determine whether patients treated with PZ-128 have fewer cardiac events such as heart attack, bypass surgery or stroke compared with those persons treated with the standard of care.

Conditions

Arterial Occlusive Diseases; Coronary Artery Disease; Coronary Disease; Arteriosclerosis; Heart Diseases; Myocardial Ischemia; Vascular Diseases; Acute Coronary Syndrome

Keywords

Platelets; Platelet Aggregation Inhibitors; Protease-Activated Receptor 1; Hemorrhage

Outcome Measures

Primary Outcomes (1)

• First Occurrence of Major Plus Minor Thrombolysis in Myocardial Infarction (TIMI) Bleeding Events; Number/Percentage of Observed Participants With Outcome Measure Events During the Study (Primary Safety)

  All suspected bleeding events positively adjudicated by CEC in a blinded fashion, were used in the reporting of the number/percentage of observed participants with a first occurrence of a TIMI major or minor bleeding event.

  From initiation of study drug up to 30 days following study drug

Secondary Outcomes (2)

• First Occurrence of Major Adverse Cardiovascular Event (MACE); Number/Percentage of Observed Participants With Outcome Measure Events During the Study (Secondary Efficacy)

  From randomization up to 30 days following study drug

• First Occurrence of Major Adverse Cardiovascular Event (MACE); Number/Percentage of Observed Participants With Outcome Measure Events During the Study (Secondary Efficacy)

  From randomization up to 90 days following study drug

Study Arms (3)

PZ-128 0.3 mg/kg

EXPERIMENTAL

PZ-128, 0.3 mg/kg, in 250 cc 5% dextrose, single dose, 2-hour intravenous infusion

Drug: PZ-128

PZ-128 0.5 mg/kg

EXPERIMENTAL

PZ-128, 0.5 mg/kg, in 250 cc 5% dextrose, single dose, 2-hour intravenous infusion

Drug: PZ-128

Placebo

PLACEBO COMPARATOR

Placebo, in 250 cc 5% dextrose, single dose, 2-hour intravenous infusion

Drug: Placebo

Interventions

PZ-128 DRUG

PZ-128 0.3 mg/kg; PZ-128 0.5 mg/kg

Placebo DRUG

Placebo

Eligibility Criteria

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

You may qualify if:

• The subject is at least 18 years of age and may be of either sex/gender and of any race and ethnicity.
• The subject is scheduled to undergo non-emergent PCI or non-emergent cardiac catheterization with the intention of performing PCI. The following classifications of the urgency of the procedure at the time the operator decides to perform it will be used for randomization stratification:
• Elective: The cardiac catheterization procedure ± PCI can be performed on an outpatient basis or during a subsequent hospitalization without significant risk of MI or death. For stable inpatients, this is a procedure that is performed during the hospitalization for convenience and ease of scheduling only and not because the subject's clinical situation demands that the procedure be performed prior to discharge.
• Urgent: The cardiac catheterization ± PCI procedure should be performed on an inpatient basis and before discharge because of significant concerns about the risk of myocardial ischemia, MI and/or death. For subjects who are outpatients or in the emergency department at the time that the cardiac catheterization is requested, this is a procedure that would warrant hospital admission based on clinical presentation.
• There is no anticipation that the subject would require treatment with a GP IIb/IIIa inhibitor prior to the initiation of the cardiac catheterization ± PCI procedure if the subject were not a participant in the current research study, and no anticipation of use during the procedure.
• The subject is willing and able to give appropriate informed consent and complete all study-related procedures, and able to adhere to dosing and visit schedules (i.e., subject signs an approved informed consent document(s) and provides HIPAA authorization);
• The subject will undergo all of the pre-enrollment parameters according to the study protocol prior to randomization and have them completed within 14 days prior to the scheduled cardiac catheterization ± PCI procedure and study drug administration.
• Women of childbearing potential (all postmenarchal women who are \<1 year menopausal or who have not had surgical sterilization or a hysterectomy are considered to be women of child-bearing potential) must agree to use a medically accepted method of contraception from the time written informed consent is given up until 90 days following the study drug administration.

You may not qualify if:

• The subject will be excluded from entry if any of the criteria listed below are met:
• Subject is pregnant, intends to become pregnant or is breast-feeding (all women of child-bearing potential must have a negative pregnancy test result confirmed prior to randomization and it must be repeated to be within 24 hours prior to the study drug administration if necessary).
• Any of the following allergy history(s):
• History of an allergic reaction\* or contraindication to any of the following protocol-directed drugs: aspirin, heparin, P2Y12 inhibitor (clopidogrel, prasugrel, ticagrelor), antihistamines (benadryl, famotidine); or
• History of an allergic reaction\* to contrast media; or
• History of an allergic reaction\* to a drug which required emergency medical treatment;
• History of an allergic reaction\* to a Hymenoptera sting which currently necessitates the subject to carry an EpiPen/injector or the subject has been prescribed one to treat an allergic reaction to a sting.
• An allergic (anaphylactic) reaction is characterized by an adverse local or general response from exposure to an allergen involving skin/mucosal tissue manifestations (hives, pruritus, flushing, angioedema), and/or respiratory compromise (dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory flow, hypoxemia), and/or hemodynamic effects (hypo/hypertension, hypotonia, syncope).
• Participation in another research study of investigational therapy (drug or device) within the past 30 days prior to randomization or planned use of other investigational therapy(s) during this research study (until 90 days following the study drug administration).
• Subject is part of the study staff personnel directly involved with this trial, or is a family member of the study staff (clinical site or sponsor).
• Prior enrollment (randomization) in this research study.
• Any condition which could interfere with, or the treatment for which might interfere with, the conduct of the research study or which would, in the opinion of the investigator, unacceptably increase the subject's risk by participating in the research study. This would include, but is not limited to alcoholism, drug dependency or abuse, psychiatric disease, epilepsy or any unexplained blackouts.
• Evidence of an ST-segment elevation myocardial infarction (STEMI) on presentation or during current hospitalization or a history of STEMI within the past 30 days prior to randomization.
• Subject is scheduled to undergo PCI for known unprotected left main coronary artery (LMCA) disease (i.e., left main stenosis ≥50% not protected by at least 1 patent bypass graft).
• Any history of a prior stroke (hemorrhagic or ischemic) or transient ischemic attack (TIA) of any etiology.

Sponsors & Collaborators

• Tufts Medical Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• RTI International: collaborator
• Inova Fairfax Hospital: collaborator
• University of Massachusetts, Worcester: collaborator

Study Sites (3)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

UMass Memorial Medical Center

Worcester, Massachusetts, 01605, United States

Location

Inova Heart and Vascular Institute, Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Related Publications (4)

• Gurbel PA, Bliden KP, Turner SE, Tantry US, Gesheff MG, Barr TP, Covic L, Kuliopulos A. Cell-Penetrating Pepducin Therapy Targeting PAR1 in Subjects With Coronary Artery Disease. Arterioscler Thromb Vasc Biol. 2016 Jan;36(1):189-97. doi: 10.1161/ATVBAHA.115.306777.

  PMID: 26681756 BACKGROUND

• Rana R, Huang T, Koukos G, Fletcher EK, Turner SE, Shearer A, Gurbel PA, Rade JJ, Kimmelstiel CD, Bliden KP, Covic L, Kuliopulos A. Noncanonical Matrix Metalloprotease 1-Protease-Activated Receptor 1 Signaling Drives Progression of Atherosclerosis. Arterioscler Thromb Vasc Biol. 2018 Jun;38(6):1368-1380. doi: 10.1161/ATVBAHA.118.310967. Epub 2018 Apr 5.

  PMID: 29622563 RESULT

• Kuliopulos A, Gurbel PA, Rade JJ, Kimmelstiel CD, Turner SE, Bliden KP, Fletcher EK, Cox DH, Covic L; TRIP-PCI Investigators. PAR1 (Protease-Activated Receptor 1) Pepducin Therapy Targeting Myocardial Necrosis in Coronary Artery Disease and Acute Coronary Syndrome Patients Undergoing Cardiac Catheterization: A Randomized, Placebo-Controlled, Phase 2 Study. Arterioscler Thromb Vasc Biol. 2020 Dec;40(12):2990-3003. doi: 10.1161/ATVBAHA.120.315168. Epub 2020 Oct 8.

  PMID: 33028101 RESULT

• Fletcher EK, Wang Y, Flynn LK, Turner SE, Rade JJ, Kimmelstiel CD, Gurbel PA, Bliden KP, Covic L, Kuliopulos A. Deficiency of MMP1a (Matrix Metalloprotease 1a) Collagenase Suppresses Development of Atherosclerosis in Mice: Translational Implications for Human Coronary Artery Disease. Arterioscler Thromb Vasc Biol. 2021 May 5;41(5):e265-e279. doi: 10.1161/ATVBAHA.120.315837. Epub 2021 Mar 25.

  PMID: 33761760 DERIVED

MeSH Terms

Conditions

Arterial Occlusive Diseases; Coronary Artery Disease; Coronary Disease; Arteriosclerosis; Heart Diseases; Myocardial Ischemia; Vascular Diseases; Acute Coronary Syndrome; Hemorrhage

Interventions

PZ-128 peptide

Condition Hierarchy (Ancestors)

Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Athan Kuliopulos, MD, PhD
• Organization: Tufts Medical Center

athan.kuliopulos@tufts.edu

617-636-8482

Study Officials

• Athan Kuliopulos, MD, PhD

  Tufts Medical Center

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2015
• First Posted: September 25, 2015
• Study Start: May 27, 2016
• Primary Completion: September 17, 2019
• Study Completion: September 17, 2019
• Last Updated: April 16, 2025
• Results First Posted: March 9, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)