Clinical Trials Register

Summary
EudraCT Number:	2019-003927-39
Sponsor's Protocol Code Number:	BAY2976217/21170
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-08-31
Trial results	View 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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2019-003927-39

A.3

Full title of the trial

Factor XI LICA to Reduce Thrombotic Events in End-Stage Renal Disease Patients on Hemodialysis: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of BAY 2976217

A XI. Faktor LICA végstádiumú vesebetegségben szenvedő, hemodializált betegek thrombotikus eseményeinek csökkentésére: 2. fázisú, randomizált, kettős vak, placebo-kontrollos vizsgálat a több különböző dózisban alkalmazott BAY 2976217 biztonságosságának, farmakokinetikájának és farmakodinámiájának értékelésére.

A.3.1

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

Factor XI LICA to reduce thrombotic events such as heart attack and stroke in patients whose kidneys are no longer able to work as they should and require treatment to filter wastes from the blood. Focus is on the safety of BAY2976217, and the way the body absorbs, distributes and gets rid of the study drug given as multiple doses

A XI. Faktor LICA a thrombotikus események - például a szívroham és a stroke - csökkentésére olyan betegek esetén, akiknek veséi már nem képesek megfelelően működni, és kezelést igényelnek a salakanyagok vérből történő kiszűrésére. A középpontban a BAY2976217 biztonságossága áll, és az, ahogyan a szervezet felveszi, elosztja és eltávolítja a többszörös adagként beadott vizsgálati készítményt.

A.3.2

Name or abbreviated title of the trial where available

RE-THINC ESRD

A.4.1

Sponsor's protocol code number

BAY2976217/21170

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 AG
B.5.2	Functional name of contact point	Bayer Clinical Trials Contact
B.5.3	Address:
B.5.3.1	Street Address	-
B.5.3.2	Town/ city	Berlin
B.5.3.3	Post code	13342
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4930300139003
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	BAY 2976217 100mg/ml Solution for injection
D.3.2	Product code	BAY 2976217
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not available
D.3.9.1	CAS number	2380288-85-5
D.3.9.2	Current sponsor code	BAY 2976217
D.3.9.3	Other descriptive name	ION-957943, BAY 2976217 (ION-957943)
D.3.9.4	EV Substance Code	SUB208553
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

End Stage Renal Disease requiring hemodialysis

E.1.1.1

Medical condition in easily understood language

Kidneys are no longer able to work as they should and require treatment to filter wastes and water from the blood

E.1.1.2

Therapeutic area

Not possible to specify

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	PT
E.1.2	Classification code	10077512
E.1.2	Term	End stage renal disease
E.1.2	System Organ Class	10038359 - Renal and urinary disorders

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	10019480
E.1.2	Term	Hemodialysis
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	10066639
E.1.2	Term	Myocardial infarct 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	10049165
E.1.2	Term	Cerebrovascular accident prophylaxis
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

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 evaluate the safety of BAY2976217 compared to placebo

E.2.2

Secondary objectives of the trial

To evaluate the PK and PD of BAY2976217

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Two types of PK/PD sampling will be performed: regular PK/PD sampling in the majority of the participants, and alternative PK/PD sampling in a subset of approximately 24-40 participants.

E.3

Principal inclusion criteria

- Participant must be at least 18 years of age at the time of signing the ICF.
- Participants with ESRD on HD for ≥3 months at the time of signing of the ICF, receiving dialysis at least 9 hours a week and stable in the view of the investigator
- Male and/or female (contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies)
- Capable of giving signed ICF as described in the Protocol, which includes compliance with the requirements and restrictions listed in the ICF and in the
protocol

E.4

Principal exclusion criteria

- Participants receiving antiplatelet therapy except daily ASA ≤ 150 mg/day
- Participants receiving anticoagulation in therapeutic doses, other than standard anticoagulation during the hemodialysis procedure
- Known inherited bleeding disorder e.g. von-Willebrand disease or Hemophilia A, B or C
- Recent (<6 months before screening) clinically significant bleeding, or at high risk of bleeding (in the judgement of the investigator)
- Recent (<3 months before screening) thromboembolic event, e.g. acute coronary syndrome, stroke, or VTE (except dialysis access thrombosis)
- Recent (<3 months before screening) major surgery or scheduled major surgery during participation in the study
- Scheduled living donor renal transplant during study participation
- Known Hepatitis B or C
- Known HIV with recent documented detectable viral load (<3 months before screening)
- Persistent heart failure as classified by the New York Heart Association classification of 3 or higher
- Life expectancy less than 6 months
- Sustained uncontrolled hypertension (persistent measurements of diastolic blood pressure ≥ 100 mmHg, and/or systolic blood pressure ≥180 mmHg)
- Hepatic disease associated with either: coagulopathy leading to a clinically relevant bleeding risk, or ALT > 3x ULN, or total bilirubin >2x ULN with direct bilirubin > 20% of the total
- Hb < 9.0 g/dL at screening
- Platelet count < 120,000 mm3 at screening
- Known hypersensitivity to the investigational drug or to inactive constituents of the study intervention
- Active malignancy requiring treatment during study participation (except nonmelanoma skin cancer, or cervical carcinoma in situ)
- Participation in a study with an investigational medicinal product within 30 days or within 5 half-lives of the previous administered drug, whichever is longer, prior to the screening/observational period (Note: Participants from previous BAY 2306001/ISIS 416858 and BAY 2976217 / ION 957943 studies are eligible)
- Any other conditions, which, in the opinion of the investigator or Sponsor would make the subject unsuitable for inclusion

E.5 End points

E.5.1

Primary end point(s)

The incidence of major bleeding and clinically-relevant non-major bleeding during the main treatment period, as assessed by blinded Central Independent Adjudication Committee (CIAC)

E.5.1.1

Timepoint(s) of evaluation of this end point

Up to 24 weeks

E.5.2

Secondary end point(s)

1- Incidence and severity of TEAEs
2- Trough concentrations for 3 dose levels of BAY 2976217
3- Maximum change in FXI antigen levels during the main treatment period
4- Maximum change in FXI activity levels during the main treatment period

E.5.2.1

Timepoint(s) of evaluation of this end point

Up to 24 weeks

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

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

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

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

Belgium

Bulgaria

Canada

Czech Republic

Germany

Greece

Hungary

Japan

Latvia

Russian Federation

Spain

Ukraine

United States

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

LVLS

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

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:

187

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

153

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

181

F.4.2.2

In the whole clinical trial

340

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)

Standard of Care treatment

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

2020-10-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-09-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-05-12

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