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

Phase 2

Completed

• Conditions: Myocardial Infarction; STEMI - ST Elevation Myocardial Infarction; Vascular Diseases; Coronary Disease; Heart Diseases
• Interventions: Drug: RUC-4 Compound

• Registration Number: NCT04284995
• Lead Sponsor: CeleCor Therapeutics

Brief Summary

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.

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 Timeline

• Study First Submitted: 2020-02-22
• Study First Submitted QC: 2020-02-25
• Study First Posted: 2020-02-26
• Study Start: 2020-06-02
• Primary Completion: 2020-11-08
• Study Completion: 2020-12-14
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-01
• Last Update Posted: 2021-02-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 27

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1	RUC-4 Compound	Cohort 1: 0.075 mg/kg RUC-4. 8 STEMI Patients will be enrolled.
Cohort 2	RUC-4 Compound	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.
Cohort 3	RUC-4 Compound	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.

Primary Outcome Measures

Name	Time	Method
Platelet aggregation	240 minutes	Inhibition of platelet aggregation
Platelet Inhibition	15 minutes	Inhibition of Platelet aggregation
Platelet inhibition	180 minutes	Inhibition of Platelet aggregation
RUC-4 Concentration	240 minutes	concentration in blood (ng/mL)
Safety and Tolerability	Hospital discharge	Bleeding events, Injection site reactions,vital signs, ECG, laboratory results

Trial Locations

Locations (1)

St. Antonius hospital; 🇳🇱 Nieuwegein, CM, Netherlands