Atrial Fibrillation (AF)
Conditions
Keywords
abelacimab, randomized, placebo-controlled, double-blind, endpoint evaluation, atrial fibrillation
Brief summary
A study to evaluate the effect of abelacimab relative to placebo on the rate of ischemic stroke or systemic embolism (SE) in patients with Atrial Fibrillation (AF) who have been deemed by their responsible physicians or by their own decision to be unsuitable for oral anticoagulation therapy.
Detailed description
Patients enrolled in the study are randomized in a 1:1 ratio to receive abelacimab 150 mg SC or matching placebo once monthly. The study is comprised of 3 periods: 1) screening period of up to 60 days, 2) an event-driven, double-blind treatment period (abelacimab 150 mg SC or matching placebo) completed after at least 111 patients have experienced an adjudicated primary endpoint event, and 3) EoT visit in core part followed by either (i) a 30-day follow-up period (EoS for core part) OR (ii) an optional OLE beginning at the EoT visit for eligible patients to receive open-label abelacimab treatment. The optional extension will only be offered to patients following regulatory and ethics approval in participating countries.
Interventions
BIOLOGICALAbelacimab
Abelacimab provided as liquid in vial (150 mg/mL)
DRUGPlacebo
Dosage Formulation: Liquid (in vial) Dose Strength: Placebo to Abelacimab
Sponsors
Anthos Therapeutics, Inc.
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient is able to understand and has provided written informed consent to participate in the trial * Diagnosed Atrial Fibrillation (AF) or atrial flutter (documented on an electrocardiogram (ECG) or monitor recording) * Age 65-74 and a CHA2DS2VASc ≥4 OR age ≥75 and a CHA2DS2VASc ≥3 * Patient is judged by the responsible physician to be unsuitable for oral anticoagulation because the risks outweigh the benefits or the patient is unwilling to take oral anticoagulation AND this determination was made prior to and independent of the study * At least 1 bleeding risk factor such as severe renal insufficiency, planned daily use of antiplatelet medication for the duration of the trial, history of bleeding from a critical area, or other conditions associated with increased risk of bleeding such as chronic nonsteroidal anti-inflammatory drug (NSAID) use, frailty or multiple falls * Patient is judged by the responsible physician to be unsuitable for left atrial appendage (LAA) closure or occlusion device, an approved device is not available, or the patient is unwilling to undergo the procedure AND this determination was made prior to and independent of the study
Exclusion criteria
* AF due to an ongoing acute reversible cause (e.g., cardiac surgery, pulmonary embolism (PE), untreated hyperthyroidism, alcohol use) * Patients who within 60 days prior to randomization (1) received a vitamin K antagonists (VKA) (e.g., warfarin, phenprocoumon, acenocoumarol) or a direct oral anticoagulant (DOAC) such as, dabigatran, rivaroxaban, apixaban, or edoxaban or (2) were newly diagnosed with AF * Patients with an intracranial or intraocular bleed within the 3 months prior to screening or any history of spontaneous intracerebral hemorrhage at any time in the absence of antithrombotic treatment * Any stroke within 14 days before randomization or transient ischemic attack (TIA) within 3 days before randomization * Mechanical heart valve or valve disease that is expected to require mechanical valve replacement intervention (surgical or invasive) during the course of the study * Patients on dialysis at screening or who are planned to start dialysis within 6 months Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Time to first event of ischemic stroke or systemic embolism (SE) | Up to 30 months | Undetermined strokes will be counted as ischemic strokes |
| Safety: Time to first occurrence of Bleeding Academic Research Consortium (BARC) type 3c/5 bleeding | Up to 30 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Time to first event of ischemic stroke, systemic embolism (SE), myocardial infarctions (MI), venous thromboembolism (VTE), or acute limb ischemia | Up to 30 months | Abelacimab versus placebo with regard to the composite of ischemic stroke, SE, MI, VTE, or acute limb ischemia |
| Efficacy: Time to first event of ischemic stroke, systemic embolism (SE), or Bleeding Academic Research Consortium (BARC) type 3c/5 bleeding event | Up to 30 months | — |
| Efficacy: Cardiovascular (CV) mortality | Up to 30 months | — |
| Efficacy: All-cause mortality | Up to 30 months | — |
| Time to first event of ischemic stroke, systemic embolism (SE), myocardial infarctions (MI), venous thromboembolism (VTE), acute limb ischemia, or International Society on Thrombosis and Haemostasis (ISTH) major bleeding | Up to 30 months | Abelacimab versus placebo with regard to net clinical outcome defined as the composite of ischemic stroke, SE, MI, VTE, acute limb ischemia, or International Society on Thrombosis and Haemostasis (ISTH) major bleeding |
Countries
Argentina, Brazil, Bulgaria, Canada, Chile, China, Colombia, Croatia, Czechia, Estonia, Finland, Germany, Greece, Hungary, India, Israel, Italy, Japan, Latvia, Malaysia, Mexico, Peru, Philippines, Poland, Puerto Rico, Romania, Serbia, Slovakia, South Africa, South Korea, Spain, Sweden, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTAnthos Therapeutics a Novartis Company
Outcome results
None listed