Clinical trial NCT04284995: A Phase 2 Open Label Study to Assess the PK/PD Properties of RUC-4 in Patients With a ST-elevation Myocardial Infarction
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronary Disease
Myocardial Infarction
Heart Diseases
Vascular Diseases
STEMI - ST Elevation Myocardial Infarction
Lead sponsor: CeleCor Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: St. Antonius Hospital
name: Diagram B.V.
First posted: 2020-02-26
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Platelet Inhibition
timeFrame: Baseline
measure: Platelet Inhibition
timeFrame: 15 minutes
measure: Platelet inhibition
timeFrame: 45 minutes
measure: Platelet inhibition
timeFrame: 60 minutes
measure: Platelet inhibition
timeFrame: 90 minutes
measure: Platelet inhibition
timeFrame: 120 minutes
measure: Platelet inhibition
timeFrame: 180 minutes
measure: RUC-4 Concentration
timeFrame: Baseline
measure: RUC-4 Concentration
timeFrame: 15 minutes
measure: RUC-4 Concentration
timeFrame: 45 minutes
measure: RUC-4 Concentration
timeFrame: 90 minutes
measure: RUC-4 Concentration
timeFrame: 120 minutes
measure: RUC-4 Concentration
timeFrame: 180 minutes
measure: Safety and Tolerability
timeFrame: Baseline
measure: Safety and Tolerability
timeFrame: Hospital discharge
measure: RUC-4 Concentration
timeFrame: 240 minutes
measure: Platelet aggregation
timeFrame: 240 minutes
Secondary outcomes:
Other outcomes:
Locations:
city: Nieuwegein
country: Netherlands
facility: St. Antonius hospital
state: CM
Study officials:
References: