Clinical Trials Register

Summary
EudraCT Number:	2022-000758-28
Sponsor's Protocol Code Number:	19767
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2022-10-19
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2022-000758-28

A.3

Full title of the trial

A multicenter, international, randomized, active comparator-controlled, double-blind, double-dummy, parallel-group, 2-arm, Phase 3 study to compare the efficacy and safety of the oral FXIa inhibitor asundexian (BAY 2433334) with apixaban for the prevention of stroke or systemic embolism in male and female participants aged 18 years and older with atrial fibrillation at risk for stroke

Ensayo fase III multicéntrico, internacional, aleatorizado, controlado con un comparador activo, doble ciego, con doble simulación y 2 grupos paralelos, para comparar la eficacia y la seguridad del inhibidor oral de FXIa asundexian (BAY 2433334) con apixaban para la prevención del ictus o embolia sistémica en participantes masculinos y femeninos de 18 años o más con fibrilación auricular y riesgo de ictus.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A study to learn how well the study treatment asundexian works and how safe it is compared to apixaban to prevent stroke or systemic embolism in people with irregular and often rapid heartbeat (atrial fibrillation), and at risk for stroke

Ensayo para conocer cómo funciona el tratamiento con asundexian y su seguridad en comparación con apixaban para prevenir el ictus o la embolia sistémica en personas con latidos cardíacos irregulares y a menudo rápidos (fibrilación auricular) y con riesgo de ictus.

A.3.2

Name or abbreviated title of the trial where available

Oral faCtor Eleven A iNhibitor asundexIan as novel antithrombotiC - AF study

Inhibidor oral del Factor Once A, asundexian como nuevo antocoagulante - ensayo OCEANIC AF

A.4.1

Sponsor's protocol code number

19767

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Bayer AG
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Bayer AG
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Bayer
B.5.2	Functional name of contact point	Bayer Clinical Trials Contact
B.5.3	Address:
B.5.3.1	Street Address	Müllerstrasse 178
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	13342
B.5.3.4	Country	Germany
B.5.6	E-mail	clinical-trials-contact@bayer.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Asundexian
D.3.2	Product code	BAY 2433334
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Asundexian
D.3.9.1	CAS number	2064121-65-7
D.3.9.2	Current sponsor code	BAY 2433334
D.3.9.4	EV Substance Code	SUB218206
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Eliquis
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb/Pfizer EEIG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Apixaban
D.3.9.1	CAS number	503612-47-3
D.3.9.3	Other descriptive name	Apixaban coated tablet 2.5 mg
D.3.9.4	EV Substance Code	SUB25425
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Eliquis
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb/Pfizer EEIG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Apixaban
D.3.9.1	CAS number	503612-47-3
D.3.9.3	Other descriptive name	Apixaban coated tablet 5 mg
D.3.9.4	EV Substance Code	SUB25425
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 3
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Prevention of stroke or systemic embolism in atrial fibrillation

Prevención del ictus y la embolia sistémica en pacientes con fibrilación auricular.

E.1.1.1

Medical condition in easily understood language

Prevention of stroke (caused by blocked blood supply to a part of brain) and blood clots travelling through the blood stream to plug another vessel in people with irregular and often rapid heartbeat

Prevención de ictus (causados por el bloqueo del suministro de sangre a una parte del cerebro) y coágulos de sangre, en personas con latidos cardíacos irregulares y a menudo rápidos.

E.1.1.2

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10049165
E.1.2	Term	Cerebrovascular accident prophylaxis
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10049910
E.1.2	Term	Thromboembolism prophylaxis
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10003658
E.1.2	Term	Atrial fibrillation
E.1.2	System Organ Class	10007541 - Cardiac disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

- To demonstrate that asundexian is superior (at least non-inferior) when compared with apixaban for prevention of stroke and systemic embolism in participants with atrial fibrillation at risk for stroke
- To demonstrate that asundexian is superior to apixaban as assessed by International Society on Thrombosis and Hemostasis (ISTH) major bleeding in participants with atrial fibrillation at risk for stroke
- To demonstrate that asundexian is superior to apixaban with respect to benefit and risk

- Demostrar que asundexian es superior (al menos no inferior) en comparación con apixaban para la prevención del ictus y la embolia sistémica en participantes con fibrilación auricular y riesgo de ictus.
- Demostrar que asundexian es superior a apixaban según la evaluación de hemorragia mayor de la ISTH (International Society on Thrombosis and Haemostasis [Sociedad Internacional de Trombosis y Hemostasia]) en participantes con fibrilación auricular y riesgo de ictus.
- Demostrar que asundexian es superior a apixaban en cuanto a beneficio y riesgo.

E.2.2

Secondary objectives of the trial

- To compare the effects of asundexian and apixaban with respect to composite and individual efficacy endpoints
- To compare asundexian and apixaban with respect to composite and individual bleeding endpoints
- To compare the benefit and risk of asundexian and apixaban with respect to a composite of efficacy and safety endpoints

- Comparar los efectos de asundexian y apixaban con respecto a los criterios de valoración de eficacia combinados e individuales.
- Comparar asundexian y apixaban con respecto a los criterios de valoración combinados e individuales.
- Comparar el beneficio y el riesgo de asundexian y apixaban con respecto a una combinación de criterios de valoración de eficacia y seguridad.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. 18 years of age or older (at legal age of consent according to local legislation) at the time of signing the informed consent
2. Atrial fibrillation documented by ECG evidence with an indication for indefinite treatment with an oral anticoagulant
3. CHA2DS2-VASc score ≥ 3 if male or ≥ 4 if female,
OR
CHA2DS2-VASc score of 2 if male or 3 if female and
enrichment criteria.

1. 18 años de edad o más (en edad legal de consentimiento según la legislación local) en el momento de firmar el consentimiento informado.
2. Fibrilación auricular confirmada por ECG con una indicación para tratamiento indefinido con un anticoagulante oral.
3. puntuación de CHA2DS2-VASc ≥ 3 si es hombre o ≥ 4 si es mujer,
O
puntuación de CHA2DS2-VASc de 2 si es hombre o 3 si es mujer y criterios de enriquecimiento.

E.4

Principal exclusion criteria

1. Mechanical heart valve prosthesis
2. Moderate-to-severe mitral stenosis at the time of inclusion into the study
3. Atrial fibrillation only due to reversible cause
4. Requirement for chronic anticoagulation for a different indication than atrial fibrillation

1. Prótesis valvulares cardíacas mecánicas.
2. Estenosis mitral de moderada a grave en el momento de la inclusión en el estudio.
3. Fibrilación auricular solo de causa reversible.
4. Necesidad de anticoagulación crónica por una indicación diferente de la fibrilación auricular.

E.5 End points

E.5.1

Primary end point(s)

1. Time to first occurrence of composite of stroke or systemic embolism
2. Time to first occurrence of ISTH major bleeding
3. Time to first occurrence of composite of stroke, systemic embolism, or ISTH major bleeding

- Tiempo hasta la primera aparición de la combinación de ictus o embolia sistémica.
- Tiempo hasta la primera aparición de hemorragia mayor según la ISTH.
- Tiempo hasta la primera aparición de la combinación de ictus, embolia sistémica o hemorragia mayor según la ISTH.

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to 34 months

Hasta 34 meses.

E.5.2

Secondary end point(s)

1. Time to first occurrence of composite of ischemic stroke or systemic embolism
2. Time to first occurrence of all-cause mortality
3. Time to first occurrence of ischemic stroke
4. Time to first occurrence of cardiovascular (CV) death
5. Time to first occurrence of composite of CV death, stroke, or myocardial infarction
6. Time to first occurrence of composite of ISTH major or clinically relevant non-major bleeding
7. Time to first occurrence of clinically relevant non-major bleeding
8. Time to first occurrence of hemorrhagic stroke
9. Time to first occurrence of intracranial hemorrhage
10. Time to first occurrence of fatal bleeding
11. Time to first occurrence of minor bleeding
12. Time to first occurrence of composite of stroke, systemic embolism, ISTH major bleeding, or all-cause mortality
13. Time to first occurrence of composite of disabling stroke (modified Rankin Scale (mRS) ≥ 3), critical bleeding, or all-cause mortality

1. Tiempo hasta la primera aparición de la combinación de ictus isquémico o embolia sistémica.
2. Tiempo hasta la primera aparición de mortalidad por todas las causas.
3. Tiempo hasta la primera aparición de ictus isquémico.
4. Tiempo hasta la primera aparición de mortalidad por causas CV.
5. Tiempo hasta la primera aparición de la combinación de mortalidad por causas CV, ictus o infarto de miocardio.
6. Tiempo hasta la primera aparición de la combinación de hemorragia mayor o no mayor clínicamente relevante según la ISTH.
7. Tiempo hasta la primera aparición de la hemorragia no mayor clínicamente relevante.
8. Tiempo hasta la primera aparición de ictus hemorrágico.
9. Tiempo hasta la primera aparición de hemorragia intracraneal.
10. Tiempo hasta la primera aparición de hemorragia mortal.
11. Tiempo hasta la primera aparición hemorragia menor.
12. Tiempo hasta la primera aparición de la combinación de ictus, embolia sistémica, hemorragia mayor según la ISTH o mortalidad por todas las causas.
13. Tiempo hasta la primera aparición de la combinación de ictus incapacitante (mRS ≥3), hemorragia crítica o mortalidad por todas las causas.

E.5.2.1

Timepoint(s) of evaluation of this end point

Up to 34 months

Hasta 34 meses.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Biomarkers

Biomarcadores

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Doble simulación

Double dummy

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

apixaban

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

494

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Argentina

Australia

Brazil

Canada

China

Colombia

Israel

Japan

Korea, Republic of

Malaysia

Singapore

Taiwan

United States

Austria

Estonia

Finland

France

Latvia

Lithuania

Poland

Sweden

Bulgaria

Netherlands

Romania

Spain

Switzerland

Czechia

Germany

Greece

Italy

Belgium

Denmark

Hungary

Norway

Portugal

Slovakia

Turkey

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last visit of the last subject

Última visita del último paciente.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

6000

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

12000

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

298

F.4.2

For a multinational trial

F.4.2.1

In the EEA

10118

F.4.2.2

In the whole clinical trial

18000

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After completion of the study the patient will be treated with approved/available standard of care therapy as outlined in the international guidelines.

Después de completar el ensayo, el paciente será tratado con la medicación estándar aprobada/disponible, tal y como se describen en las guías internacionales.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2023-02-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2023-01-18

P. End of Trial
P.	End of Trial Status	Ongoing

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