A study to compare how safe and well tolerated study drug Abelacimab (MAA868) is comapred to another drug called Rivaroxaban in patients with heart condition that causes an irregular and abnormally fast heart rate.

Phase 1

Conditions: Atrial Fibrillation
MedDRA version: 20.0Level: PTClassification code 10003658Term: Atrial fibrillationSystem Organ Class: 10007541 - Cardiac disorders
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2020-004507-13-PL

Lead Sponsor: Anthos Therapeutics

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1200

Inclusion Criteria

1. Able to provide written informed consent before the first study assessment is performed
2. Male and female patients = 55 years old
3. History of AF or atrial flutter with planned indefinite anticoagulation. Patients with newly diagnosed AF are eligible.
4. 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

Extension period inclusion criteria:
Patients eligible for inclusion in the extension period must fulfill all the
following criteria:
1. Ongoing study treatment for the randomized part of the trial at the
EoT visit
2. Able to provide written informed consent to enter the extension
period

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1000

Exclusion Criteria

1. 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
2. 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
3. Patients with an intracranial or intraocular bleed within the 3 months prior to screening
4. Clinically significant mitral stenosis (valve area <1.5 cm2)
5. Mechanical heart valve or other indication for anticoagulation therapy
other than atrial fibrillation (e.g., venous thromboembolism)
6. Known presence of an atrial myxoma or left ventricular thrombus
7. History of left atrial appendage closure or removal
8. Active endocarditis
9. Systolic BP >180 mm Hg or diastolic BP >100 mm Hg on repeated measurements at screening
10. Planned invasive procedure with potential for uncontrolled bleeding (e.g. major surgery)
11. Any stroke within 14 days before randomization or TIA within 3 days before randomization
12. A CrCl <15 mL/min or on dialysis at the time of Screening
13. Platelet count =70,000/mm3 at the Screening Visit
14. Hemoglobin <8 g/dL at the Screening Visit
15. aPTT or PT >1.5x the upper limit of normal (ULN) at the Screening Visit, if the patient is anticoagulant-naïve
16. 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 t

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: • To evaluate the effect of abelacimab relative to rivaroxaban on the rate of major or clinically relevant non-major (CRNM) bleeding events;Secondary Objective: • To evaluate the effect of abelacimab relative to rivaroxaban on the rate of major bleeding events<br>• To evaluate the effect of abelacimab relative to rivaroxaban on the rate of major or minor bleeding events<br><br>;Primary end point(s): • Time to first event of composite of International Society on Thrombosis and Haemostasis (ISTH)-defined major bleeding or CRNM bleeding events <br>;Timepoint(s) of evaluation of this end point: Time to first event

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Time to first event ISTH-defined major bleeding events <br>Time to first event ISTH-defined major or minor bleeding events;Timepoint(s) of evaluation of this end point: Time to first event

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