Clinical trial NCT03487445: A Medical Research Study to Evaluate the Effects of ACT-246475 in Adults With Heart Attack
Official title: A Multi-center, Open-label, Randomized, Study to Assess the Onset of Platelet Aggregation Inhibition After a Single Subcutaneous Injection of ACT-246475 in Adults With Acute Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myocardial Infarction
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2018-04-04
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this study is to find out how fast a drug called selatogrel (ACT-246475) can prevent platelets from binding together. This study will also help to find out more about the safety of this new drug. The drug selatogrel (ACT-246475) will be used in 2 different doses (8 mg or 16 mg) and will be administered in the thigh.

Detailed description: This study is planned in patients presenting with Acute Myocardial Infarction (AMI) scheduled for an invasive strategy. Platelet activation and thrombus formation play a pivotal role in the pathophysiology of acute coronary syndrome. Early platelet inhibition has been shown to reduce the risk of recurrent events after a myocardial infarction.

The screening period starts when the participant provides informed consent and ends with participant's randomization. Eligible participants had an acute myocardial infarction (AMI; ST-segment elevation myocardial infarction \[STEMI\] or non-ST-elevation myocardial infarction \[NSTEMI\]), a life-threatening condition, and will therefore fulfill the ICH-GCP definition of vulnerable subjects ("persons in emergency situations"). Accordingly, a specific process for obtaining consent in compliance with local regulations and approved by the independent ethics committee will be implemented.

The study will be performed during a participant's hospital stay related to the qualifying AMI.

Standard treatment of AMI is allowed including anticoagulants. Ticagrelor will be the only oral P2Y12 receptor antagonist allowed to be initiated during the study and its administration will be possible only after selatogrel administration. Use of fibrinolytics or GPIIb/IIIa inhibitors will be prohibited unless required for bail-out. All other standard-of-care treatments for AMI will be allowed without restriction.

The treatment period starts with the participant's randomization and ends after the end-of-study assessments, approximately 48 hours after the administration of a single study treatment dose.

Eligibility criteria: Main Inclusion Criteria:

* Informed consent obtained prior to any study-mandated procedure,
* Males aged from 18 to 85 and postmenopausal females aged up to 85 years,
* Onset of symptoms of AMI of more than 30 min and less than 6 hours prior to randomization,
* Subjects presenting a type I AMI including STEMI or NSTEMI.

Main Exclusion Criteria:

* Cardiogenic shock or severe hemodynamic instability,
* Cardiopulmonary resuscitation,
* Loading dose of any oral P2Y12 receptor antagonist prior to randomization,
* Planned fibrinolytic therapy or any fibrinolytic therapy administered within 24 h prior to randomization,
* Known platelet disorders (e.g., thromboasthenia, thrombocytopenia, von Willebrand disease).
* Active internal bleeding, or bleeding diathesis or conditions associated with high risk of bleeding.
* Known clinically important anemia.
* Oral anticoagulation therapy within 7 days prior to randomization

Primary outcomes:
measure: Number of Participants With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation
timeFrame: 30 minutes after the administration of the subcutaneous injection
Secondary outcomes:
Other outcomes:
measure: Number of Participants (Per-protocol Subgroup) With a Pharmacodynamic Response as Assessed by the Inhibition of Platelet Aggregation
timeFrame: 30 minutes after the administration of the subcutaneous injection
measure: Number of Participants With a Pharmacodynamic Response Within the First Hour as Assessed by the Inhibition of Platelet Aggregation
timeFrame: pre-dose, 15, 30 and 60 minutes after the administration of the subcutaneous injection
measure: Absolute Platelet Reactivity (P2Y12 Reaction Units) Over Time
timeFrame: pre-dose, 15, 30 and 60 minutes after administration of the subcutaneous injection
measure: Maximum Selatogrel Plasma Concentration (Cmax)
timeFrame: pre-dose, 15, 30 and 60 minutes and 8 hours after the administration of the subcutaneous injection
measure: Time to Reach Maximum Selatogrel Plasma Concentration (Tmax)
timeFrame: pre-dose, 15, 30 and 60 minutes and 8 hours after the administration of the subcutaneous injection
Locations:
city: Aalst
country: Belgium
facility: OLV Ziekenhuis Aalst
city: Leuven
country: Belgium
facility: UZLeuven
city: Nahariya
country: Israel
facility: Galilee Medical Center
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: Bern
country: Switzerland
facility: University Hospital Bern
city: Lugano
country: Switzerland
facility: Cardiocentro Ticino
Study officials:
affiliation: Idorsia Pharmaceuticals Ltd.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Gurbel PA, Bliden KP, Butler K, Antonino MJ, Wei C, Teng R, Rasmussen L, Storey RF, Nielsen T, Eikelboom JW, Sabe-Affaki G, Husted S, Kereiakes DJ, Henderson D, Patel DV, Tantry US. Response to ticagrelor in clopidogrel nonresponders and responders and effect of switching therapies: the RESPOND study. Circulation. 2010 Mar 16;121(10):1188-99. doi: 10.1161/CIRCULATIONAHA.109.919456. Epub 2010 Mar 1.
citation: Jernberg T, Payne CD, Winters KJ, Darstein C, Brandt JT, Jakubowski JA, Naganuma H, Siegbahn A, Wallentin L. Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease. Eur Heart J. 2006 May;27(10):1166-73. doi: 10.1093/eurheartj/ehi877. Epub 2006 Apr 18.
citation: Parodi G, Bellandi B, Valenti R, Migliorini A, Marcucci R, Carrabba N, Giurlani L, Gensini GF, Abbate R, Antoniucci D. Comparison of double (360 mg) ticagrelor loading dose with standard (60 mg) prasugrel loading dose in ST-elevation myocardial infarction patients: the Rapid Activity of Platelet Inhibitor Drugs (RAPID) primary PCI 2 study. Am Heart J. 2014 Jun;167(6):909-14. doi: 10.1016/j.ahj.2014.03.011. Epub 2014 Apr 4.
citation: Sinnaeve P, Fahrni G, Schelfaut D, Spirito A, Mueller C, Frenoux JM, Hmissi A, Bernaud C, Ufer M, Moccetti T, Atar S, Valgimigli M. Subcutaneous Selatogrel Inhibits Platelet Aggregation in Patients With Acute Myocardial Infarction. J Am Coll Cardiol. 2020 May 26;75(20):2588-2597. doi: 10.1016/j.jacc.2020.03.059.