A Study To Determine the Efficacy and Safety of REG1 Compared to Bivalirudin in Patients Undergoing PCI (Regulate)

A Randomized, Open-Label, Multi-Center, Active-Controlled, Parallel Group Study To Determine the Efficacy and Safety of the REG1 Anticoagulation System Compared to Bivalirudin in Patients Undergoing Percutaneous Coronary Intervention

This study is designed to determine the efficacy of REG1 compared to bivalirudin in preventing periprocedural ischemic complications and major bleeding in patients undergoing PCI as a treatment for CAD. Bivalirudin has been studied in patients undergoing PCI in both ACS (NSTEMI and unstable angina [UA]) and elective PCI. In comparison to UFH, bivalirudin has shown similar rates of ischemic events while demonstrating a significant reduction in bleeding and an improved net clinical benefit.

Evidence from previous studies indicates that pegnivacogin represents an extremely potent, chemically unique anticoagulant that can be reversed by anivamersen across multiple populations (refer to Section 1.2.2). The question that still remains is whether Factor IX (FIX) inhibition by pegnivacogin can result in fewer ischemic events than a previously studied agent while active control with anivamersen can preserve the benefit of reduced bleeding. The purpose of this study is to evaluate REG1 in an adequately powered definitive study with an open-label, multi-center, active-controlled, randomized design to answer that question.

Study Overview

• Status: Terminated
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Bivalirudin; Drug: pegnivacogin/anivamersen

• Study Type: Interventional
• Enrollment (Actual): 3232
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Black Hills Cardiovascular Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The study population will consist of patients with CAD undergoing PCI. Three key subgroups will be included
2. Willing and able to sign an Institutional Review Board/Ethics Committee (IRB/EC) approved informed consent prior to any study-related activities;
3. Male or female age 18 or greater;
4. If female of childbearing potential, must have a negative urine or serum pregnancy test or be post-menopausal for at least 1 year prior to randomization. Females of childbearing potential must be practicing adequate birth control to be eligible. It is the Investigator's responsibility for determining whether the patient has adequate birth control for study participation;
5. Subject is able and willing to comply with the protocol and all study procedures

Exclusion Criteria:

1. Acute ST-segment elevation myocardial infarction within 48 hours of randomization;
2. Evidence of current clinical instability
3. Evidence of a contraindication to anticoagulation or increased risk of bleeding
4. Use of any investigational drug or device within 30 days of randomization or the planned use of an investigational drug or device through EOS (Day 30 follow-up);
5. Use of the select antithrombotic agents
6. Baseline hemoglobin (Hgb) <9 g/dL or equivalent;
7. Baseline estimated glomerular filtration rate (GFR) ≤ 10 mL/min/1.73m² or currently undergoing renal replacement therapy (hemodialysis or peritoneal dialysis);
8. Baseline platelet count <100,000/mm3;
9. Known allergy or intolerance to aspirin, to all available ADP/P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor), or to bivalirudin or REG1 (or any of their respective components);
10. The following planned procedures: a. Planned staged PCI procedure within 3 days after randomization; b. Planned CABG or valve surgery within 30 days after randomization;
11. Any other medical or psychiatric condition that in the Investigator's judgment precludes participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bivalirudin; Bivalirudin bolus and infusion	Drug: Bivalirudin; Other Names: Angiox, Angiomax
Experimental: Reg 1 (pegnivacogin/anivamersen); Bolus pegnivacogin plus anivamersen active control agent	Drug: pegnivacogin/anivamersen; Other Names: Reg 1 Anticoagulation System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ischemic composite	The primary efficacy endpoint is the composite of death, nonfatal myocardial infarction, nonfatal stroke and urgent TLR through Day 3.	Day 3

Collaborators and Investigators

• Sponsor: Regado Biosciences, Inc.
• Collaborators: Icahn School of Medicine at Mount Sinai; The Cleveland Clinic; Parexel; Duke Clinical Research Institute; Canadian VIGOUR Centre
• Investigators: Study Director: Steven L Zelenkofske, DO, FACC, Regado Biosciences; Principal Investigator: A. Michael Lincoff, MD, The Cleveland Clinic; Principal Investigator: John H Alexander, MD, MHS, Duke Clinical Research Institute

Publications and helpful links

General Publications

• Park EJ, Choi J, Lee KC, Na DH. Emerging PEGylated non-biologic drugs. Expert Opin Emerg Drugs. 2019 Jun;24(2):107-119. doi: 10.1080/14728214.2019.1604684. Epub 2019 Apr 19.
• Lincoff AM, Mehran R, Povsic TJ, Zelenkofske SL, Huang Z, Armstrong PW, Steg PG, Bode C, Cohen MG, Buller C, Laanmets P, Valgimigli M, Marandi T, Fridrich V, Cantor WJ, Merkely B, Lopez-Sendon J, Cornel JH, Kasprzak JD, Aschermann M, Guetta V, Morais J, Sinnaeve PR, Huber K, Stables R, Sellers MA, Borgman M, Glenn L, Levinson AI, Lopes RD, Hasselblad V, Becker RC, Alexander JH; REGULATE-PCI Investigators. Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI): a randomised clinical trial. Lancet. 2016 Jan 23;387(10016):349-356. doi: 10.1016/S0140-6736(15)00515-2. Epub 2015 Nov 5. Erratum In: Lancet. 2016 Mar 19;387(10024):1162. Boudoulas, Dean [corrected to Boudoulas, Konstantinos D.].

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: May 2, 2013
• First Submitted That Met QC Criteria: May 6, 2013
• First Posted (Estimate): May 7, 2013

Study Record Updates

• Last Update Posted (Estimate): October 23, 2014
• Last Update Submitted That Met QC Criteria: October 22, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Percutaneous Coronary Intervention; Acute Coronary Syndrome; Regado; Reg 1; bivalirudin
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Bivalirudin
• Other Study ID Numbers: REG1-CLIN310; 2013-001384-23 (EudraCT Number)