A Phase 2 Open Label Study to Assess the PK/PD Properties of RUC-4 in Patients With a ST-elevation Myocardial Infarction (CEL-02)

A Phase 2 Open Label Study to Assess the PK and PD Properties of a Single Subcutaneous Injection of RUC-4 in Patients With a ST-elevation Myocardial Infarction Presenting to the Cardiac Catheterization Lab With Planned Primary Coronary Angioplasty

RUC-4 is a novel, promising and fast acting (5-15 minutes) αIIbβ3 receptor antagonist with a high-grade inhibition of platelet aggregation (≥80%) shortly after subcutaneous administration. This study is designed to extend the findings in CEL-01 to patients with ST-elevation myocardial Infarction (STEMI) presenting to the cardiac catheterization laboratory with planned coronary angioplasty.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction; Heart Diseases; Vascular Diseases; Coronary Disease; STEMI - ST Elevation Myocardial Infarction
• Intervention / Treatment: Drug: RUC-4 Compound

Detailed Description

RUC-4 is a novel, promising and fast acting (5-15 minutes) αIIbβ3 receptor antagonist with a high-grade inhibition of platelet aggregation (≥80%) shortly after subcutaneous administration. For patients with ST-elevation myocardial infarction (STEMI) early treatment with RUC-4 could be beneficial by improving initial patency of the infarct related vessel and by minimizing thrombotic occlusions, thus improving both coronary artery and myocardial microvascular blood flow, possibly resulting in a decrease in infarct size and a reduction in complications of STEMI.

The purpose of this study is to assess the PD and PK properties of a single subcutaneous injection of RUC-4 in STEMI patients presenting to the cardiac catheterization laboratory with planned coronary angioplasty. In addition the safety and tolerability will be assessed at baseline and hospital discharge.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • CM
    • Nieuwegein, CM, Netherlands, 3435
      • St. Antonius Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with STEMI, presenting with persistent chest pain (>30 min) and ≥1 mm ST-segment elevation in two adjacent electrocardiograph leads, with >6 mm cumulative ST-segment deviation, in whom the total duration of symptoms to first intracoronary device deployment (excluding a wire) is anticipated to be within 6 hours
2. Adult males and females 18 years of age or older
3. Females must be non-pregnant, non-lactating, and of non-childbearing potential (postmenopausal or surgically sterilized) by history and review of medical record
4. Weight (by history) of between 52 and 120 kg
5. Written informed consent (following short-form of the informed consent form at Cardiac Catheterization Lab)

Exclusion Criteria:

1. High probability in the opinion of the cardiologist that current STEMI is caused by stent thrombosis and the previous PCI related to this stent thrombosis is <1 month
2. High suspicion of type II MI
3. Out of hospital cardiac arrest (OHCA)
4. Therapy resistant cardiogenic shock (systolic blood pressure ≤80 mm Hg for >30 minutes)
5. Persistent severe hypertension (systolic blood pressure >180 mm Hg or diastolic blood pressure >110 mm Hg)
6. Current active coronavirus disease 2019 (COVID-19) infection (criteria according to local guidelines)
7. Known severe liver disease
8. Known history of severe renal dysfunction (glomerular filtration rate <30 mL/min or serum creatinine >200 mmol/L [>2.5 mg/dL])
9. Known left bundle branch block
10. Requirement of oral anticoagulation (Vitamin K antagonists {VKA} or direct oral antagonists {DOACs})
11. Current treatment with αIIbβ3 receptor antagonist (other than RUC-4)
12. Coagulation abnormality, known bleeding disorder, or history of documented prior hemorrhagic or thrombotic stroke within the past 6 months
13. History of upper or lower GI bleeding within the past 6 months
14. Known clinically important anemia
15. Known clinically important thrombocytopenia (platelet count of less than 150,000/μL)
16. Known history of allergy to any of the ingredients in the RUC-4 formulation (i.e., acetate buffer, sucrose)
17. Major surgery within the past 6 months
18. Life expectancy of less than 6 months
19. Any clinically significant abnormality identified prior to enrollment that in the judgment of the Investigator would preclude safe completion of the study
20. Unwillingness or inability to comply with the requirements of this protocol including the presence of any condition (physical, mental, or social) that is likely to affect the patient's ability to comply with the study protocol

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Cohort 1: 0.075 mg/kg RUC-4. 8 STEMI Patients will be enrolled.	Drug: RUC-4 Compound; All patients will receive a single subcutaneous dose of RUC-4 in the Cardiac Catheterization Lab (CCL) before coronary angiography/percutaneous coronary intervention.
Experimental: Cohort 2; Cohort 2: Dose of RUC-4 selected by Safety Review Committee (SRC) after completion of Cohort 2 and review of data. 8 STEMI Patients will be enrolled.	Drug: RUC-4 Compound; All patients will receive a single subcutaneous dose of RUC-4 in the Cardiac Catheterization Lab (CCL) before coronary angiography/percutaneous coronary intervention.
Experimental: Cohort 3; Cohort 3: Dose of RUC-4 selected by Safety Review Committee (SRC) after completion of Cohort 2 and review of data. 8 STEMI Patients will be enrolled.	Drug: RUC-4 Compound; All patients will receive a single subcutaneous dose of RUC-4 in the Cardiac Catheterization Lab (CCL) before coronary angiography/percutaneous coronary intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet Inhibition	Inhibition of Platelet Aggregation	Baseline
Platelet Inhibition	Inhibition of Platelet aggregation	15 minutes
Platelet inhibition	Inhibition of Platelet aggregation	45 minutes
Platelet inhibition	Inhibition of Platelet aggregation	60 minutes
Platelet inhibition	Inhibition of Platelet aggregation	90 minutes
Platelet inhibition	Inhibition of Platelet aggregation	120 minutes
Platelet inhibition	Inhibition of Platelet aggregation	180 minutes
RUC-4 Concentration	concentration in blood (ng/mL)	Baseline
RUC-4 Concentration	concentration in blood (ng/mL)	15 minutes
RUC-4 Concentration	concentration in blood (ng/mL)	45 minutes
RUC-4 Concentration	concentration in blood (ng/mL)	90 minutes
RUC-4 Concentration	concentration in blood (ng/mL)	120 minutes
RUC-4 Concentration	concentration in blood (ng/mL)	180 minutes
Safety and Tolerability	Bleeding events, Injection site reactions,vital signs, ECG, laboratory results	Baseline
Safety and Tolerability	Bleeding events, Injection site reactions,vital signs, ECG, laboratory results	Hospital discharge
RUC-4 Concentration	concentration in blood (ng/mL)	240 minutes
Platelet aggregation	Inhibition of platelet aggregation	240 minutes

Collaborators and Investigators

• Sponsor: CeleCor Therapeutics
• Collaborators: Diagram B.V.; ST. Antonius hospital Nieuwegein

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2020
• Primary Completion (Actual): November 8, 2020
• Study Completion (Actual): December 14, 2020

Study Registration Dates

• First Submitted: February 22, 2020
• First Submitted That Met QC Criteria: February 25, 2020
• First Posted (Actual): February 26, 2020

Study Record Updates

• Last Update Posted (Actual): February 3, 2021
• Last Update Submitted That Met QC Criteria: February 1, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Cardiovascular Diseases; Myocardial Infarction; Infarction; Heart Diseases; Coronary Disease; ST Elevation Myocardial Infarction; Vascular Diseases
• Other Study ID Numbers: CEL-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes