A Phase 3 Study of Zalunfiban in Subjects With ST-elevation MI

ST-elevation Myocardial Infarction (STEMI) Clinical Trial

— CELEBRATE  

Official title:

A Phase 3 Prospective, Blinded, Randomized, Placebo Controlled, International Multicenter Study to Assess the Safety and Efficacy of a Single SQ Injection of Zalunfiban in Subjects With ST-elevation MI in the Pre-hospital Setting

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04825743
• Other study ID #: CEL-03
• Status: Recruiting
• Phase: Phase 3
• Start date: April 24, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2024
• Source: CeleCor Therapeutics
• Contact: Robert S Hillman, PhD
• Phone: 8587779750
• Email: rhillman[@]celecor.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 3 prospective, blinded, randomized, placebo controlled, international multicenter study. Subjects with STEMI will be enrolled in the ambulance if they meet all eligibility criteria. These subjects will be evaluated by (para)medics who transport the subjects to the participating hospitals in Europe and North America. Hospitals and ambulance services with experience in ambulance studies will be selected. Each subject will receive a single subcutaneous injection containing either zalunfiban Dose 1 (0.110 mg/kg) or zalunfiban Dose 2 (0.130 mg/kg) or placebo

Description:

Subjects will be screened in the ambulance based on the information available; those fulfilling the eligibility criteria who have provided verbal witnessed/short written/Exception from Informed Consent Requirements (EFIC) process informed consent will be randomized and enrolled in the study. Following a single weight-based dose of subcutaneous study drug administered by the ambulance staff, the patient will be transferred to the clinical site PCI center for angiography and intervention.

Regular standard of care is performed from the provision of informed consent through the last study mandated subject visit. Concomitant medications will be recorded. Treatment with IV P2Y12 antagonists or other αIIbβ3 receptor before PCI/angiography is prohibited. Demographics, concomitant medications, vital signs, and medical history will be collected in the CRF. Adverse events, bleeding events and injection site reactions will be collected. Angiography and PCI details will be recorded. Full written informed consent will be obtained. Additional blood samples for safety will be collected at 1, 6, 24 and 72 hours (or hospital discharge) post-PCI/angiography. Blood samples for high-sensitive cardiac troponin T (upon arrival and 24 hours post PCI/angiography) and NT-ProBNP (24 hours post PCI/angiography) will be assessed by central laboratory. Follow up phone contacts will occur at 30 days to report AEs, bleeding events, and injection site reactions, and 12-months to record mortality, and hospitalizations for heart failure or atrial fibrillation, and [in the event of stroke], 90 days (±2 weeks) to record the stroke disability.

Angiography/PCI data and ECGs will be evaluated at independent Core Laboratories. An independent, blinded Clinical Events Committee will provide central adjudication of all clinical endpoint events. A DSMB will examine the safety data in an ongoing manner and to alert the Steering Committee in case of clinically concerning safety issues that should lead to consideration of altering the trial, and can recommend modification of the study protocol based on pre-specified rules.

The duration of participation for each subject will be 12 months (± 1 month), including enrollment, study drug administration, hospitalization, and phone contact follow-up at 30 days (+ 7 days) and 12 months (± 1 month).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2499
• Est. completion date: December 31, 2024
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Males aged =18 years or post-menopausal or surgically sterile females =50 years or =55 years (for Czech Republic study sites only).

2. Weight (by history) between 52 and 130 kg.

3. Subjects with STEMI, presenting with persistent ischemic chest pain (>10 minutes) and new =2 mm ST-segment elevation in two adjacent ECG leads, in whom the total duration of symptoms is 4 hours maximum. If time of symptom onset is uncertain, the cardiologist may be contacted to confirm inclusion criteria.

4. Exception from Informed Consent Requirements (EFIC) process, verbal witnessed/ short written informed consent, or written informed consent signed by subject or legally authorized representative/independent witness will be obtained in the acute phase by (para)medics, according to local applicable legal regulations. Subject is willing and able to give informed consent. Written informed consent will be obtained as soon as the subject's clinical condition allows it.

Exclusion Criteria:

1. Cardio Pulmonary Resuscitation (CPR) for current Out of Hospital Cardiac Arrest (OHCA).

2. Presenting with systolic blood pressure <90 mmHg (confirmed on repeat assessment) and heart rate >100 beats per minute (bpm).

3. Current known active coronavirus disease 2019 (COVID-19) infection (criteria according to local guidelines).

4. Currently treated with renal dialysis.

5. Current treatment with oral anticoagulation (Vitamin K antagonists [VKA], direct oral anticoagulants [DOACs]), or thrombolytic agents.

6. Major surgery, or trauma or bleeding leading to hospitalization, within the past month.

7. Known history of ischemic or hemorrhagic stroke.

8. Known severe anemia (regular blood transfusion needed).

9. Previously enrolled in this study.

10. Participation in another clinical study with an investigational product or device within the past month.

11. Life expectancy less than one year.

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Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction
• ST Elevation Myocardial Infarction
• ST-elevation Myocardial Infarction (STEMI)

Intervention

Drug:
• zalunfiban
zalunfiban is a novel small molecule inhibitor of the platelet aIIbß3 receptor specifically designed for first medical contact therapy of ST-elevation myocardial infarction (STEMI).
• Placebo
A placebo will be prepared to those subjects assigned to placebo. Less than 1 mL (depending on subject's weight) will be administered by subcutaneous injection.

Locations

Country	Name	City	State
Canada	University of Alberta	Edmonton
Czechia	St. Anne's University hospital	Brno
Czechia	University Hospital Brno	Brno
France	European Hosital de Paris - GVM Care & Research (La Roseraie)	Aubervilliers
France	Henri Mondor University Hospital	Créteil
France	André Grégoire Hospital - GHT GPNE	Montreuil
France	Bichat-Claude Bernard Hospital	Paris
France	European Hospital Georges-Pompidou (HEGP)	Paris
France	Lariboisière Hospital AP-HP	Paris
France	University Hospital De La Pitié-Salpêtrière	Paris
Hungary	Semmelweis University Heart and Vascular Center	Budapest
Hungary	Bacs-Kiskun County Teaching Hospital	Kecskemét
Netherlands	Jeroen Bosch Ziekenhuis	's-Hertogenbosch
Netherlands	Amsterdam UMC	Amsterdam
Netherlands	Amsterdam UMC, locatie AMC	Amsterdam
Netherlands	Rijnstate Arnhem	Arnhem
Netherlands	Tergooi Blaricum	Blaricum
Netherlands	Amphia Ziekenhuis	Breda
Netherlands	Slingeland Ziekenhuis	Doetinchem
Netherlands	Ziekenhuis Gelderse Vallei	Ede
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	Zuyderland MC	Heerlen	Limberg
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Maastricht UMC	Maastricht
Netherlands	St. Antonius Ziekenhuis	Nieuwegein
Netherlands	ETZ TweeSteden	Tilburg
Netherlands	UMC Utrecht	Utrecht
Netherlands	Viecuri Medisch Centrum	Venlo
Netherlands	Isala	Zwolle
Romania	Emergency Clinical Hospital "Bagdasar-Arseni", Bucharest	Bucharest
Romania	Emergency University Hospital Bucharest	Bucharest
Romania	Institute of Cardiovascular Diseases "Prof. George I.M. Georgescu" Iasi	Iasi
Romania	Emergency Clinical County Hospital Targu-Mures	Târgu-Mures

Sponsors (1)

Lead Sponsor	Collaborator
CeleCor Therapeutics

Countries where clinical trial is conducted

Canada,  Czechia,  France,  Hungary,  Netherlands,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	primary efficacy -clinical outcome	As assessed by a 7-point scale. The 7 outcomes, ranking from worst to best are: Death (all cause) at 30 days follow-up; Stroke at 30 days follow-up; Recurrent MI (type 1 to 4 MI) at 30 days follow-up; Acute stent thrombosis at 24 hours post-PCI/angiography; New onset heart failure or rehospitalization for heart failure at 30 days follow-up; MI with hs-cTnT levels =10x ULN at 24 hours post-PCI/angiography; None of the above	at 30 days follow-up after a single subcutaneous injection of zalunfiban versus placebo
Primary	primary safety- bleeding events [BARC criteria]	• To assess bleeding events (according to Global Use of Strategies to Open Occluded Coronary Arteries [GUSTO] severe or life threatening criterion for safety assessment and according to the Bleeding Academic Research Consortium [BARC] 3C and 5 criteria for information only)	after a single subcutaneous injection of zalunfiban versus placebo at 30 days post-PCI/angiography
Secondary	secondary efficacy-restoration of the coronary artery blood flow	To assess restoration of the culprit coronary artery blood flow (corrected Thrombolysis in Myocardial Infarction [TIMI] Frame Count) before intended PCI (or post coronary angiography in case no PCI is performed) after a single subcutaneous injection of zalunfiban versus placebo	before PCI (or coronary angiography if no PCI is performed)
Secondary	efficacy-resolution of ST segment deviation	To assess resolution of ST segment deviation post-PCI/angiography after a single subcutaneous injection of zalunfiban versus placebo	1 hour post-PCI/angiography
Secondary	Efficacy-composite of all cause death, recurrent MI, acute stent thrombosis or blinded bail-out use of IV aIIbß3 antagonists or IV P2Y12 antagonist	To assess a composite of all cause death, recurrent MI, acute stent thrombosis or blinded bail-out use of IV aIIbß3 antagonists or IV P2Y12 antagonist	at 30 days follow-up after a single subcutaneous injection of zalunfiban versus placebo
Secondary	Efficacy-acute stent thrombosis	To assess incidence of definite, probable or possible acute stent thrombosis after a single subcutaneous injection of zalunfiban versus placebo	up to 24 hours post-PCI
Secondary	Safety throughout the study by AE reporting	Recording of AEs and SAEs fibrillation up to 12-months follow-up	AEs up to 30 days follow-up; SAEs up to resolution/stabilization, the SAEs mortality, hospitalization for heart failure and atrial fibrillation up to 12-months follow-up
Secondary	Safety-platelet count	To assess platelet count after a single subcutaneous injection of zalunfiban versus placebo	before PCI/angiography, at the end of the PCI/angiography, 6 and 24 hours post-PCI/angiography and at hospital discharge/72-hours post-PCI/angiography (whichever occurs first)
Secondary	Safety-bleeding events (ISTH and TIMI)	To assess bleeding events (according to International Society on Thrombosis and Haemostasis [ISTH] Major and TIMI Major for information only) after a single subcutaneous injection of zalunfiban versus placebo	at 30 days follow-up
Secondary	Safety-bleeding events (GUSTO mild and moderate, BARC type 2, 3 and 5, ISTH minor and/or major and TIMI minor and major)	To assess incidence of bleeding events according to GUSTO mild and moderate criteria, BARC type 2, 3 and 5 criteria, ISTH minor and or major bleeding, TIMI minor and major criteria	30 days follow-up
Secondary	Safety-injection site reactions	To assess the injection site reactions of a single subcutaneous injection of zalunfiban versus placebo	baseline, 1-hour post-PCI/angiography, hospital discharge/72-hours post-PCI/angiography, and at 30 days follow-up