ABELACIMAB for Atrial fibrillation

Inclusion criteria

• {"criterion_text":"- Able to provide written informed consent before the first study assessment is performed.\n- Male and female patients ≥ 55 years old.\n- History of AF or atrial flutter with planned indefinite anticoagulation. Patients with newly diagnosed AF are eligible.\n- A CHA2DS2-VASc of ≥4 OR a CHA2DS2-VASc of ≥3 with at least 1 of the following: • Planned concomitant use of antiplatelet medication (e.g. aspirin and/or P2Y12 inhibitor) for the duration of the trial. • CrCl ≤50 ml/min by the Cockcroft-Gault equation.\n- Extension period inclusion criteria: Ongoing study treatment for the randomized part of the trial at the EoT visit.\n- Extension period inclusion criteria: Able to provide written informed consent to enter the extension period."}

Exclusion criteria

• {"criterion_text":"- Use of other investigational drugs within 5 half-lives prior to enrollment or until the expected pharmacodynamic effect has returned to baseline, whichever is longer.\n- Planned invasive procedure with potential for uncontrolled bleeding (e.g. major surgery).\n- Any stroke within 14 days before randomization or TIA within 3 days before randomization.\n- A CrCl <15 mL/min or on dialysis at the time of Screening.\n- Platelet count ≤70,000/mm3 at the Screening Visit.\n- Hemoglobin <8 g/dL at the Screening Visit.\n- aPTT or PT >1.5x the upper limit of normal (ULN) at the Screening Visit, if the patient is anticoagulant-naïve.\n- Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they agree to use highly effective methods of contraception during their participation in the trial and for at least 10 weeks after the last dose of abelacimab for women randomized to abelacimab. Highly effective contraception methods include: • Total abstinence (when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception • Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment • Male sterilization of sexual partner (at least 6 months prior to screening). For female patients in the study, the vasectomized male partner should be the sole partner for that patient • Use of oral (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception. Hormonal contraceptive methods should not be used or encouraged if considered to be contraindicated. In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking investigational drug. Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of reported menopausal status or oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment with follicle stimulating hormone (FSH) is she considered not of child-bearing potential.\n- Sexually active males with female partners who are WOCBP must agree to use a condomor use other reliable birth control methods during their time in the study and should notfather a child or donate sperm during the study period.\n- History of drug addiction or alcohol abuse in the past 2 years, as judged by the Investigator.\n- Significant illness which has not resolved within two (2) weeks prior to the start of the study drug.\n- History of hypersensitivity to any of the study drugs (including rivaroxaban) or its excipients, to drugs of similar chemical classes, or any contraindication listed in the label for rivaroxaban.\n- Any medical or psychiatric condition which in the judgment of the Investigator may preclude patients of complying with study requirements for the duration of the study.\n- Extension period exclusion criteria: History of hypersensitivity to abelacimab.\n- Extension period exclusion criteria: Patients with an intracranial or intraocular bleed within the 3 months prior to EoT.\n- Extension period exclusion criteria: Clinically significant mitral stenosis (valve area <1.5 cm2) Mechanical heart valve or other indication for anticoagulation therapy other than atrial fibrillation (e.g., venous thromboembolism).\n- Extension period exclusion criteria: Known presence of an atrial myxoma or left ventricular thrombus.\n- Extension period exclusion criteria: History of left atrial appendage closure or removal.\n- Patients with an intracranial or intraocular bleed within the 3 months prior to screening.\n- Clinically significant mitral stenosis (valve area <1.5 cm2).\n- Mechanical heart valve or other indication for anticoagulation therapy other than atrial fibrillation (e.g., venous thromboembolism).\n- Known presence of an atrial myxoma or left ventricular thrombus.\n- History of left atrial appendage closure or removal.\n- Active endocarditis.\n- Systolic BP >180 mm Hg or diastolic BP >100 mm Hg on repeated measurements at screening."}

Primary endpoints

• {"endpoint_text":"- Time to first event of composite of International Society on Thrombosis and Haemostasis (ISTH)-defined major bleeding or CRNM bleeding events.","definition_or_measurement_approach":"Time-to-event measure: time to first occurrence of a composite endpoint defined as ISTH-defined major bleeding or clinically relevant non-major (CRNM) bleeding events (ISTH definitions used)."}

Secondary endpoints

• {"endpoint_text":"- Time to first event ISTH-defined major bleeding events.","definition_or_measurement_approach":"Time-to-event measure: time to first occurrence of an ISTH-defined major bleeding event."}
• {"endpoint_text":"- Time to first event ISTH-defined major or minor bleeding events.","definition_or_measurement_approach":"Time-to-event measure: time to first occurrence of ISTH-defined major or minor bleeding events."}

Czechia

Earliest CTIS Part Ii Submission Date

19-01-2024

Latest Decision Or Authorization Date

13-03-2026

Processing Time Days

784

Number Of Sites

14

Number Of Participants

247

Hungary

Earliest CTIS Part Ii Submission Date

19-01-2024

Latest Decision Or Authorization Date

13-03-2026

Processing Time Days

784

Number Of Sites

13

Number Of Participants

362

Poland

Earliest CTIS Part Ii Submission Date

19-01-2024

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

787

Number Of Sites

16

Number Of Participants

287

Primary sponsor

Full Name

Anthos Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Fortrea Inc.

Responsibilities

sponsorDuties codes: 1,10,11,12,2,6,7,8,9

Name

Parexel International (IRL) Limited

Responsibilities

sponsorDuties codes: 12,8

Third parties

• {"country":"United States","full_name":"TIMI Study Group","duties_or_roles":"sponsorDuties codes: 2","organisation_type":"Industry"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Diagnostic Services Limited","duties_or_roles":"Drug labelling and distribution; sponsorDuties code 3","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"Routine clinical pathology testing; clinical chemistry, haematology, microbiology; histopathology; serology/endocrinology; analytical chemistry; primary/surrogate endpoint test.","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"sponsorDuties codes: 1,10,11,12,2,6,7,8,9","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"sponsorDuties codes: 12,8","organisation_type":"Pharmaceutical company"}