Testing glenzocimab to treat heart attack and understand how it works
| ISRCTN | ISRCTN15443962 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15443962 |
| EudraCT/CTIS number | 2022-001054-32 |
| IRAS number | 1005400 |
| Secondary identifying numbers | RG_22-013 |
- Submission date
- 27/01/2023
- Registration date
- 25/08/2023
- Last edited
- 14/04/2025
- Recruitment status
- Stopped
- Overall study status
- Stopped
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
Glenzocimab is a medication that blocks thrombosis, which is an abnormal type of blood clotting that occurs during heart attacks and strokes. Unlike existing anti-blood clotting medications, glenzocimab is thought to have minimal effect on normal types of blood clotting that prevent bleeding. The aim of this trial is to determine if glenzocimab reduces the damage caused by a heart attack in patients presenting with a big heart attack also known as ST-segment elevation myocardial infarction (STEMI). The aim of the study is to determine whether glenzocimab is a safe and effective treatment for large heart attacks. We will assess its effectiveness by determining whether it reduces heart damage, by measuring this using a heart scan called a cardiac MRI after 3 months. Glencozimab (previously known as ACT017) is a Fab fragment of a monoclonal antibody, which inhibits the platelet glycoprotein VI (GPVI) receptor. GPVI has a major role in thrombosis triggered by atherosclerotic plaque (such as during a heart attack or stroke) but appears to have a minimal role in haemostasis. In a phase I clinical trial, glenzocimab did not have a significant effect on bleeding. In preliminary results, glenzocimab was not associated with an increased risk of bleeding in phase 2 studies of patients with stroke or COVID. Although we are not expecting an increased risk of bleeding, we will closely monitor for bleeding. The GPVI receptor is only present on platelets and monoclonal antibodies have highly specific effects on the receptor that they target. Off-target effects are therefore not expected, thereby reducing the risk of adverse reactions.
Who can participate?
Patients with STEMI
What does the study involve?
Over 15 months, patients will be recruited from two centres in the UK (Birmingham and Sheffield). Patients will be randomised to receive either glenzocimab or placebo as soon as they arrive in the hospital. Patients will otherwise receive standard care, including percutaneous coronary intervention, which is the emergency procedure that is used to unblock the blood vessels around the heart (coronary arteries). Patients will be closely monitored for any side effects and their condition will be monitored.
What are the possible benefits and risks of participating?
Patients will be monitored closely in the catheter laboratory during the procedure (after the infusion has started) for any acute adverse effects followed by close monitoring in the Coronary Care Unit (CCU) where the patient will stay for 24 hours as per routine care. They will also have further monitoring on the wards until their discharge. The patient will be given safety net advice prior to discharge and also contact details of the research team if they have any concerns after their discharge. We do not anticipate any long-term effects of the medication due to the short half-life of glencozimab.
At 90 days the patient will have cardiac magnetic resonance imaging (CMR), which is a form of non-invasive imaging that does not involve ionising radiation. All patients have a safety questionnaire form filled out routinely prior to CMR to ensure their eligibility. CMR is safe and routinely performed on patients with heart conditions including heart attacks with heart failure. The patient will be informed of having CMR prior to discharge and will be allowed to ask any questions.
Where is the study run from?
Queen Elizabeth Hospital, Birmingham (UK)
When is the study starting and how long is it expected to run for?
January 2023 to April 2025
Who is funding the study?
Acticor Biotech (France)
Who is the main contact?
LIBERATE Trials Office, Liberate@trials.bham.ac.uk
Contact information
Principal Investigator
University Hospitals Birmingham NHS Foundation Trust
Queen Elizabeth Hospital
Department of Cardiology
Birmingham
B15 2TH
United Kingdom
 ORCID ID |
0000-0002-5881-5806 |
|---|---|
| Phone | +44 (0)121 371 4623 |
| John.Townend@uhb.nhs.uk |
Public
University of Birmingham
Birmingham
B15 2TT
United Kingdom
| Liberate@trials.bham.ac.uk |
Study information
| Study design | Randomized double-blind placebo-controlled study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | A phase II, randomised, double-bLInd, placeBo-controllEd tRiAl To invEstigate the efficacy and safety of glenzocimab and the mechanism of inhibiting platelet GPVI as a treatment for ST-elevation myocardial infarction (LIBERATE) |
| Study acronym | LIBERATE |
| Study objectives | Primary objective: To assess whether glenzocimab reduces myocardial infarct size in patients with ST-elevation myocardial infarction. Secondary objectives: 1. To assess the effect of glenzocimab on the improvement in indices of microvascular obstruction 2. To assess the effect of glenzocimab on the improvement in indices of myocardial damage 3. To assess the effect of glenzocimab on the reduction in platelet activity 4. To assess the effect of glenzocimab on the reduction of systemic inflammation 5. To assess the safety profile of glenzocimab by reporting deaths, serious adverse events (SAE), Suspected Unexpected Serious Adverse Reactions (SUSARs) and bleeding-related events |
| Ethics approval(s) |
Approved 22/08/2023, East Midlands - Derby Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 207 104 8236; derby.rec@hra.nhs.uk), ref: 23/EM/0045 |
| Health condition(s) or problem(s) studied | ST-elevation myocardial infarction |
| Intervention | The LIBERATE trial is a double-blind trial for participants who have had an ST-elevation Myocardial Infarction (STEMI). Participants will be randomised using an online bespoke database on a 1:1 basis and receive either glenzocimab (humanized monoclonal antibody fragment (fab) directed against the human platelet glycoprotein VI (GPVI), and a novel antithrombotic drug, the investigational medicinal product (IMP)) or a matched placebo. 1g of IMP or placebo will be given intravenously during the emergency Primary Percutaneous Coronary Intervention procedure and last 6 hours in total. There are two follow-up visits 30 and 90 days after the intervention. |
| Intervention type | Biological/Vaccine |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Glenzocimab |
| Primary outcome measure | Myocardial infarct size as a percentage of left ventricular (LV) mass measured using delayed gadolinium-enhanced cardiovascular magnetic resonance (CMR) imaging at 90 days (± 21 days) post-myocardial infarction |
| Secondary outcome measures | 1. Resolution of ST-elevation measured using serial 12-lead ECGs at days 1, 2 and 3 (if still an inpatient) 2. Restoration of Thrombolysis in Myocardial Infarction (TIMI) 3 flow and myocardial blush grade measured using coronary angiography at the time of the therapeutic procedure 3. Collagen-induced platelet aggregation measured using Multiple Electrode Aggregometry on day 1 4. Area under the curve of serum troponin and CK-MB levels measured in the hospital laboratory over the 48 hours post-myocardial infarction 5. Inflammation assessed through serial high-sensitivity C-reactive protein (CRP) levels measured in serum using a CRP test at days 1, 2, 3 (if still an inpatient) and 30 6. Safety profile of glenzocimab: deaths, SAEs, SUSARs, bleeding-related events and treatment-emergent adverse events measured using study records throughout the trial until day 90 |
| Overall study start date | 25/01/2023 |
| Completion date | 30/04/2025 |
| Reason abandoned (if study stopped) | Lack of funding/sponsorship |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 212 |
| Key inclusion criteria | 1. Informed consent (including emergency consent) 2. Age ≥ 18 years 3. Confirmation of the diagnosis of ST-elevation myocardial infarction by the clinical team on the basis of history and ECG findings 4. Intention to proceed with primary percutaneous coronary intervention (PCI) 5. Presentation within 6 hours of chest pain |
| Key exclusion criteria | 1. Inability to provide consent 2. All women of childbearing potential (WOCBP) are excluded from study entry. Women are only classed as non-WOCBP if they meet 1 or more of the following criteria: 2.1. Premenopausal female with documented hysterectomy 2.2. Premenopausal female with documented bilateral salpingectomy or oophorectomy 2.3. Postmenopausal female defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using contraception or hormonal replacement therapy (HRT). However, in the absence of 12 months of amenorrhoea, a single FSH measurement is insufficient. 3. Active bleeding 4. Known thrombocytopenia (with platelet count < 100,000/µl in last 12 months) 5. Known renal impairment (with estimated Glomerular Filtration Rate (eGFR) < 30ml/minute in last 12 months) 6. Left bundle branch block on ECG 7. Suspected non-thrombotic cause (e.g. spontaneous coronary artery dissection, vasospasm, Takotsubo cardiomyopathy) 8. Current treatment with oral anticoagulants 9. Cardiogenic shock – indicated by systolic blood pressure less than 80 mmHg or use of inotropes 10. Out of hospital cardiac arrest 11. Known history of MI or prior coronary artery bypass graft (CAGB) surgery 12. Known history of pre-existing cardiomyopathy 13. Known history of any type of intracranial haemorrhage 14. Known history of platelet function or coagulation disorder 15. Known history of any spontaneous major bleeding (indicated by bleeding requiring transfusion) 16. Known intracranial malignancy (any type) or intracranial aneurysm (any type) 17. Known history of major surgery defined as surgery involving opening a major body cavity (such as the abdomen, chest, or skull) or well-vascularised tissues (such as the colon mucosa and prostate tissue) or opening a major artery, within the last month 18. Known history of any type of surgery within the last week 19. Known history of major trauma (defined as serious injury with the potential to result in disability or death) within the last month 20. Contraindication to cardiac MRI (pacemaker, allergy to gadolinium contrast, non-MRI compatible implants or foreign bodies) 21. Known hypersensitivity to investigational medicinal product (glenzocimab) 22. Use of an investigational drug within 30 days prior to screening or 5 half-lives or twice the duration of biological effect of the investigational product (whichever is longer) 23. Known use of GPIIb/IIa inhibitor within the last 2 weeks |
| Date of first enrolment | 15/01/2024 |
| Date of final enrolment | 01/02/2025 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Mindelsohn Way
Birmingham
B15 2GW
United Kingdom
Herries Road
Sheffield
S5 7AU
United Kingdom
Sponsor information
Hospital/treatment centre
C/o: Dr Birgit Whitman
Head of Research Governance and Integrity
Research Strategy and Services Division
Research Park
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
| Phone | +44 (0)7814 650 003 |
|---|---|
| researchgovernance@contacts.bham.ac.uk | |
| Website | http://www.uhb.nhs.uk/ |
"ROR" |
https://ror.org/03angcq70 |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 31/01/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | 1. Peer reviewed scientific journals 2. Internal report 3. Conference presentation 4. Publication on website 5. Submission to regulatory authorities 6. Access to study data will be in accordance with the University of Birmingham and CRUK clinical trial unit (CRCTU) data sharing policy: https://www.birmingham.ac.uk/research/crctu/data-sharing-policy.aspx . The CRCTU has a defined procedure in place for data sharing which ensures that the necessary legal and ethical requirements are followed, and the policy is based on guidelines published by the Information Commissioners Office. |
| IPD sharing plan | Access to study data will be in accordance with the University of Birmingham and CRUK clinical trial unit (CRCTU) data-sharing policy: https://www.birmingham.ac.uk/research/crctu/data-sharing-policy.aspx. The CRCTU has a defined procedure in place for data sharing which ensures that the necessary legal and ethical requirements are followed, this policy which is based on guidelines published by the Information Commissioners Office. |
Editorial Notes
14/04/2025: The study was stopped due to lack of funding.
09/01/2024: The recruitment start date was changed from 08/01/2024 to 15/01/2024.
20/12/2023: The recruitment start date was changed from 11/12/2023 to 08/01/2024.
14/11/2023: The recruitment start date was changed from 01/11/2023 to 11/12/2023.
27/01/2023: Trial's existence confirmed by the HRA.
