A Masked, Multicentre, Placebo-controlled, Randomized Phase IIa Clinical Trial to investigate the safety and efficacy of ApTOLL in a population of ST Elevation Myocardial Infarct (STEMI) patients.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aptatargets S.L.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Decision date (initial)

2023-09-06

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Aptatargets S.L.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess ApTOLL safety at two different doses administered by i.v. bolus (0.2 mg/kg and 0.4 mg/kg) in patients who are candidates for emergency angioplasty in the setting of ST-segment elevation myocardial infarction (STEMI) and who have not received thrombolytics.

Secondary objectives 3

1. 1. To assess the biological effect of ApTOLL on the early infarct volume measured by late gadolinium enhancement-magnetic resonance imaging (LGE-MRI) at 5 (±2) days and 90 (±14) days after randomization.
2. 2. To assess the biological effect of ApTOLL on cardiac parameters and functional index by echocardiography (ECHO) at 72h (±24h) and 90 (±14) days after randomization.
3. 3. To provide an initial estimate of the biological effect of ApTOLL on blood pro-inflammatory biomarkers linked to STEMI at baseline and 24, 48 and 72 hours after randomization.

Conditions and MedDRA coding

STEMI (ST Elevation Myocardial Infarct)

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Informed consent obtained from subject or acceptable subject surrogate (i.e., next of kin, or legal representative).
2. 2. Men or Women aged ≥18 years.
3. 3. In case of women of childbearing potential (WOCBP), they must confirm menstrual period and a negative highly sensitive urine or serum pregnancy test to be included. Additionally, those WOCBP enrolled in the trial should adopt highly effective methods for birth control for a period of 7 days after dose. In case of male patients, partners of WOCBP, they must adopt highly effective methods for birth control for a period of 7 days after dose.
4. 4. Patient admitted with primary ACS with final diagnosis of first STEMI (defined by the 2017 European Society of Cardiology [ESC] guidelines[1] for STEMI based on clinical and ECG criteria* (ST-elevation in anterior wall), within 6 hours from symptom onset, who do not receive thrombolytic therapy for the treatment of STEMI. *ECG criteria for STEMI:persistent ST-elevation in anterior wall at the J-point in two contiguous leads with the cut-off points: ≥0.2 millivolt (mV) in men or ≥0.15 mV in women in leads V2-V3 and/or ≥0.1 mV in other leads).
5. 5. Patients who are suitable candidates to receive pPCI for STEMI management.

Exclusion criteria 22

1. 1. Subject has suffered an acute myocardial infarction (AMI) in the past.
2. 2. ECG pattern of damage in another wall than anterior wall.
3. 3. Subjects with any other structural cardiac disease.
4. 4. Subjects in cardiogenic shock stages C, D, or E of the SCAI (Society for Cardiovascular Angiography and Interventions) classification.
5. 5. Subjects with cardiac arrest in the presentation of the acute myocardial infarction, requiring prolonged advanced life support resuscitation.
6. 6. Past history of heart failure in NYHA (New York Heart Association) stages III or IV.
7. 7. Patients with pacemaker rhythm or complete left bundle-branch block.
8. 8. Suspected aortic dissection, presumed septic embolus, or suspicion of bacterial endocarditis or any other suspected non-type 1 myocardial infarction according to the Universal Definition of Myocardial Infarction.
9. 9. Subjects with any contraindications related to the cardiac MRI procedure (devices or metal foreign bodies, including pacemaker, defibrillator) including severe claustrophobia according to the lists/safety rules of the local MRI departments.
10. 10. Patients currently receiving, immunosupressant drugs and/or, high doses or long-term treatment with corticosteroids.
11. 11. Current severe hepatic disease.
12. 12. Known hemorrhagic diathesis, coagulation factor deficiency.
13. 13. Unable to receive antithrombotic therapy clinically recommended.
14. 14. Baseline blood glucose of <50 mg/dL or >400 mg/dL.
15. 15. Evidence of active systemic infection.
16. 16. Known current use of cocaine at time of treatment.
17. 17. Patient participating in a study involving an investigational drug or device.
18. 18. Patients that are unlikely to be available for a clinical follow-up (e.g., no fixed home address, visitor from other country).
19. 19. Female who is pregnant or lactating or has a positive pregnancy test at time of admission or WOCBP who are not using an effective method of contraception.
20. 20. History of life-threatening allergy (more than rash) to contrast medium.
21. 21. Known renal insufficiency with creatinine ≥3 mg/dL or Glomerular Filtration Rate (GFR) <30 mL/min. Creatinine clearance <30 mL/min/1.73 m2.
22. 22. Serious, advanced, or terminal illness with anticipated life expectancy of less than 1 year.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To evaluate the safety of ApTOLL in the STEMI defined population as determined by: 1. All cause death during 90 days after administration of ApTOLL 2. Incidence adverse events (AEs) during the first 72 hours after administration of treatment or until discharge (if earlier). The AEs of particular interest to this study are severe hypotension (requiring vasoactive agents), sustained ventricular arrhythmias and cardiogenic shock.

Secondary endpoints 3

1. The biological effect of ApTOLL on the early infarct volume will be measured by LGE-MRI at 5 days (±48 hours) after randomization and late changes in infarct volume at 90 (±14) days after randomization. MRI parameters to be obtained will be infarct mass, infarct size (in terms of percentage of total left ventricle mass) and left ventricular ejection fraction (LVEF). MRI will be performed by local radiologists and read by a central reader upon transfer from the site radiologist.
2. The biological effect of ApTOLL on cardiac parameters will be determined by echocardiography at 72 (±24h) and 90 (±14) days after randomization and measuring LV end-diastolic volume (LVEDV), LVEF, E-e’ ratio, trans-mitral pattern (normal, type 1, 2,3), estimated pulmonary artery pressure, inferior vena cava diameter and presence/absence of intracavitary thrombi.
3. The biological effect of ApTOLL on pro-inflammatory biomarkers will be measured by analysing the levels of IL-6, IL-1b, IL-4, IL-10, CXCL-10, serum amyloid A (SAA), Toll-like receptor 4 (TLR4), cardiac troponin T and high-sensitivity C-reactive protein (hsCRP) at baseline, 24h, 48h and 72h after randomization.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aptatargets S.L.

Sponsor organisation

Aptatargets S.L.

Address

Avenida Del Cardenal Herrera Oria 298

City

Madrid

Postcode

28035

Country

Spain

Scientific contact point

Organisation

Aptatargets S.L.

Contact name

Dr. Jose Luis Zamorano

Public contact point

Organisation

Aptatargets S.L.

Contact name

David Segarra

Third parties 1

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications