Clinical trial NCT04825743: A Phase 3 Study of Zalunfiban in Subjects With ST-elevation MI
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: ST-elevation Myocardial Infarction (STEMI)
Lead sponsor: CeleCor Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-04-01
Enrollment: 2463
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 Disaggpro(tm) zalunfiban Dose 1 (0.110 mg/kg) or Disaggpro(tm) zalunfiban Dose 2 (0.130 mg/kg) or placebo

Detailed 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).

Eligibility criteria: 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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Primary outcomes:
measure: primary efficacy -clinical outcome
timeFrame: at 30 days follow-up after a single subcutaneous injection of zalunfiban versus placebo
measure: primary safety- bleeding events [BARC criteria]
timeFrame: after a single subcutaneous injection of zalunfiban versus placebo at 30 days post-PCI/angiography
Secondary outcomes:
measure: secondary efficacy-restoration of the coronary artery blood flow
timeFrame: before PCI (or coronary angiography if no PCI is performed)
measure: efficacy-resolution of ST segment deviation
timeFrame: 1 hour post-PCI/angiography
measure: Efficacy-composite of all cause death, recurrent MI, acute stent thrombosis or blinded bail-out use of IV αIIbβ3 antagonists or IV P2Y12 antagonist
timeFrame: at 30 days follow-up after a single subcutaneous injection of zalunfiban versus placebo
measure: Efficacy-acute stent thrombosis
timeFrame: up to 24 hours post-PCI
measure: Safety throughout the study by AE reporting
timeFrame: 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
measure: Safety-platelet count
timeFrame: 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)
measure: Safety-bleeding events (ISTH and TIMI)
timeFrame: at 30 days follow-up
measure: Safety-bleeding events (GUSTO mild and moderate, BARC type 2, 3 and 5, ISTH minor and/or major and TIMI minor and major)
timeFrame: 30 days follow-up
measure: Safety-injection site reactions
timeFrame: baseline, 1-hour post-PCI/angiography, hospital discharge/72-hours post-PCI/angiography, and at 30 days follow-up
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Providence Alaska Medical Center
state: Alaska
city: Royal Oak
country: United States
facility: Corewell Health William Beaumont University Hospital
state: Michigan
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Edmonton
country: Canada
facility: University of Alberta
city: Brno
country: Czechia
facility: St. Anne's University hospital
city: Brno
country: Czechia
facility: University Hospital Brno
city: Aubervilliers
country: France
facility: European Hosital de Paris - GVM Care & Research (La Roseraie)
city: Boulogne-Billancourt
country: France
facility: Hospital Ambroise Pare
city: Créteil
country: France
facility: Henri Mondor University Hospital
city: Grenoble
country: France
facility: Grenoble Alpes University Hospital
city: Marseille
country: France
facility: University Hospital of Marseille - La Timone Hospital
city: Montreuil
country: France
facility: André Grégoire Hospital - GHT GPNE
city: Paris
country: France
facility: Bichat-Claude Bernard Hospital
city: Paris
country: France
facility: Hôpital Cochin
city: Paris
country: France
facility: Lariboisière Hospital AP-HP
city: Paris
country: France
facility: University Hospital De La Pitié-Salpêtrière
city: Rennes
country: France
facility: Regional University Hospital of Rennes - Hospital Ponchaillou
city: Budapest
country: Hungary
facility: Semmelweis University Heart and Vascular Center
city: Debrecen
country: Hungary
facility: University of Debrecen
city: Kecskemét
country: Hungary
facility: Bacs-Kiskun County Teaching Hospital
city: Mexico City
country: Mexico
facility: Instituto Nacional de Cardiologia "Ignacio Chavez"
state: D.f.
city: Heerlen
country: Netherlands
facility: Zuyderland MC
state: Limberg
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, locatie AMC
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: Arnhem
country: Netherlands
facility: Rijnstate Arnhem
city: Blaricum
country: Netherlands
facility: Tergooi Blaricum
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis
city: Doetinchem
country: Netherlands
facility: Slingeland Ziekenhuis
city: Ede
country: Netherlands
facility: Ziekenhuis Gelderse Vallei
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Maastricht UMC
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis
city: Tilburg
country: Netherlands
facility: ETZ TweeSteden
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Venlo
country: Netherlands
facility: Viecuri Medisch Centrum
city: Zwolle
country: Netherlands
facility: Isala
city: Bucharest
country: Romania
facility: Emergency Clinical Hospital "Bagdasar-Arseni", Bucharest
city: Bucharest
country: Romania
facility: Emergency University Hospital Bucharest
city: Iaşi
country: Romania
facility: Institute of Cardiovascular Diseases "Prof. George I.M. Georgescu" Iasi
city: Timişoara
country: Romania
facility: Institute for Cardiovascular Diseases Timisoara
city: Târgu-Mureş
country: Romania
facility: Emergency Clinical County Hospital Targu-Mures
Study officials:
affiliation: Maastricht University Medical Center
name: Prof. Arnoud WJ Van 't Hof, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: