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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Anthos Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

16 Apr 2021 → ongoing

Decision date (initial)

2024-02-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Anthos Therapeutics

External identifiers

EU CT number

2023-509066-38-00

EudraCT number

2020-004507-13

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Others, Pharmacodynamic

To evaluate the effect of abelacimab relative to rivaroxaban on the rate of major or clinically relevant non-major (CRNM) bleeding events

Secondary objectives 2

1. To evaluate the effect of abelacimab relative to rivaroxaban on the rate of major bleeding events
2. To evaluate the effect of abelacimab relative to rivaroxaban on the rate of major or minor bleeding events

Conditions and MedDRA coding

Atrial Fibrillation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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.
5. Extension period inclusion criteria: Ongoing study treatment for the randomized part of the trial at the EoT visit.
6. Extension period inclusion criteria: Able to provide written informed consent to enter the extension period.

Exclusion criteria 25

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 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.
17. 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.
18. History of drug addiction or alcohol abuse in the past 2 years, as judged by the Investigator.
19. Significant illness which has not resolved within two (2) weeks prior to the start of the study drug.
20. 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.
21. Extension period exclusion criteria: History of hypersensitivity to abelacimab.
22. Extension period exclusion criteria: Patients with an intracranial or intraocular bleed within the 3 months prior to EoT.
23. 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).
24. Extension period exclusion criteria: Known presence of an atrial myxoma or left ventricular thrombus.
25. Extension period exclusion criteria: History of left atrial appendage closure or removal.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to first event of composite of International Society on Thrombosis and Haemostasis (ISTH)-defined major bleeding or CRNM bleeding events.

Secondary endpoints 2

1. Time to first event ISTH-defined major bleeding events.
2. Time to first event ISTH-defined major or minor bleeding events.

Investigational products

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

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Anthos Therapeutics Inc.

Sponsor organisation

Anthos Therapeutics Inc.

Address

1 Health Plaza

City

East Hanover

Postcode

07936-1016

Country

United States

Scientific contact point

Organisation

Anthos Therapeutics Inc.

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Anthos Therapeutics Inc.

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 5

Locations

3 EU/EEA countries · 43 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 38 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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