Clinical Results Summary
A clinical study to learn about the safety and effects of edoxaban inchildren with heart conditions who are at risk of blood clots
Protocol number: DU176B-C-U313

Thank You!

Daiichi Sankyo, Inc., the sponsor of this study, would like to thank the children and theirparents or carers who took part in this study for edoxaban, also known as DU-176b. Eachchild helped to advance medical research for children with heart conditions who are at
risk of developing blood clots. Their contribution to medicine and healthcare is greatly
appreciated.

Important note: This summary only shows the results of a single study. Other studies may have different
findings. Researchers and health authorities look at the results of many studies to understand which
treatments work and how they work. It takes a lot of people in many studies around the world to advance
medical science and healthcare.
Do not use the results of this study to make health decisions. Please talk to a doctor before changing any
treatment you are taking or if you have any questions about these study results.

DU176B-C-U313 Clinical Results Summary | 1What was the main purpose of this study?
Researchers were looking for a better way to treat children with heart conditions who are at risk of developinga type of blood clot called a thromboembolism. These blood clots form in a blood vessel in the body, breakloose, are carried by the blood stream and can block another blood vessel. This is a serious condition which
can affect different organs in the body. The common symptoms include shortness of breath, pain or swellingin the leg, and reddish discoloration of the affected part of the body.
The main treatment option for thromboembolisms in children are heparins and vitamin K blockers. Heparins
are medicines that are used to prevent blood clots. Vitamin K blockers are medicines that are used to reduceclotting of blood by blocking the activity of vitamin K.
Currently, the available medicines for treating blood clots in children have many drawbacks e.g., the medicine
has to be given through injections, or close lab monitoring and many dose adjustments are required.
Edoxaban is only required to be taken once a day by mouth and does not have any drawbacks as otherstandard medicines.
In this study, researchers wanted to see how safe and effective edoxaban is at treating children with heart
conditions who are at risk of thromboembolism.

Treatments given in this study
The treatments given in this study were:

EdoxabanAn investigational treatment
being tested for the treatmentof thromboembolism inchildren with heart conditions

Standard treatment
Heparin(Enoxaparin)
Vitamin K blockers(Warfarin)

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Main goals of this study

The main questions the researchers wanted to answer in this study were:*A major bleeding event is defined as any bleeding occurring in critical parts (like brain, lungs, or stomach) of
the body caused by edoxaban or standard treatment.
** A clinically relevant non-major bleeding event is defined as any bleeding that does not meet the criteria for
major bleeding but requires treatment, hospitalization, or reduction in daily activity.

Other goals of this study

Researchers also wanted to answer the following question:
How many children who took edoxaban had a thromboembolic event*** compared to those who took
standard treatment?
*** A thromboembolic event is when a blood clot in a blood vessel breaks off and lodges elsewhere in thebody, such as the lungs.

How long was this study?
An individual child could have been in this study for
up to 13 months. The study started in May 2018 andended in December 2021. The results were collected
up to December 2021 and a study report wascreated. This summary is based on that report.

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Who was in this study?
This study included 167 children from 16 countries:

Country

No. of childrenEgypt

37

USA

33

France18

Austria15

Israel11

Turkey10

United Kingdom

8

Hungary

7

Lebanon7

Ukraine

6Canada<5India<5Russia<5Poland<5Croatia<5Spain<5

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Children could take part in this study if they:•

had a heart condition and were at a risk ofdeveloping clots in the blood vessels andrequired at least 3 months of treatment toprevent formation of blood clots,•were not at a risk of bleeding due to taking
medicines that help prevent the formation ofblood clots,•did not have mechanical heart valves,•

did not have active bleeding or were not at high risk of bleeding which meant that they were unable totake anticoagulant treatment because it may be harmful.

What happened during this study?
This was a Phase 3 study that compared the safety and effects of edoxaban with standard treatment. In
Phase 3 studies, the study treatment is given to a larger number of people with the disease condition to learn
more about the effects of the study treatment and its safety.
This study was “open label”. This means that both the researchers and the children knew which treatment wasgiven to which children.
This study included 2 treatment periods.

Main treatment period
Researchers used a computer system to assign children into two groups by a process called randomization. Itmeans that each child could be assigned to any group, and it helps to make sure the groups are distributedfairly.
The children were divided into the 2 treatment groups:•Group 1: children received different doses of edoxaban either as a tablet or liquid mixture (suspension),once daily, for 90 days. The doses given to the children were dependent on the age and the weight of thechild.

•Group 2: children received either warfarin as a tablet or enoxaparin as an injection under the skin, once
daily, for 90 days.

DU176B-C-U313 Clinical Results Summary | 5Extension period
In the extension period, all children received different doses of edoxaban either as a tablet or liquid mixture(suspension).

What were the key results of this study?
Key results from this study are shown for the total group of children as average results. This summary does notshow the results from each individual child. An individual child’s results could be different from the total groupof children. A full list of the questions the researchers wanted to answer, and a detailed presentation of theresults can be found on the websites listed at the end of this summary.

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How many children experienced a major bleeding event or a clinically relevant
non-major bleeding event during this study?
The number of children who had major or clinically relevant non-major bleeding events during the main
treatment period are mentioned in the table below:

Percentage (Number of children) who had major or clinically relevant non-major bleeding events
Edoxaban(Out of 109 children)

Standard treatment(Out of 58 children)

1% (1)

2% (1)

One child on edoxaban had a nosebleed and one child on standard treatment (heparin) had bleeding in thedigestive tract. Both events were considered as clinically relevant non-major bleeding events.
During the extension period, 1 child (out of 144) had a major bleeding event (liver injury) following an
accident, and a non-major bleeding event (nosebleed).

How long after starting treatment did the children who took edoxaban
experience a major bleeding event or a clinically relevant non-major bleeding
event compared to those who took standard treatment?
During the main treatment period, 1 child had a clinically relevant non-major bleeding event 10 days after
starting edoxaban and 1 child had a clinically relevant non-major bleeding event 58 days (about 2 months)
after starting standard treatment.
During the extension period, 1 child had a major bleeding event 224 days (more than 7 months) after starting
treatment and a clinically relevant non-major bleeding event 247 days (more than 8 months) after starting
treatment.

What were the other results of this study?
How many children who took edoxaban had thromboembolic events comparedto those who took standard treatment?
During the main treatment period, 1 child who took standard treatment had 2 thromboembolic events. Noneof the children who took edoxaban had a thromboembolic event.
During the extension period, 4 children who took edoxaban had a thromboembolic event.
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What medical problems did the children have?
Side effects are medical problems (such as a feeling tired) that happened during the study which the study
doctor (investigator) thought could be related to the treatments in the study. This section provides a summaryof side effects related to the study treatment. The websites listed at the end of this summary has more
information about the medical problems that happened in this study.
Side effects are considered serious if they cause death, are life-threatening, cause lasting problems, or require
hospitalization. Some children stop study treatment because of side effects.

How many children had serious side effects?
In this study, side effects were monitored for all children who took part in this study.

None of the children had a serious side effect or died due to a side effect during
this study.

How many children had non-serious side effects?
During the main treatment period, 6% (7 out of 109) of children who were given edoxaban reported sideeffects and 2% (1 out of 58) of children who were given standard treatment reported side effects. The mostcommon side effect, which happened in at least 2 children in any group, was nosebleed.
The other side effects happened in only 1 child each in any group. These side effects are reported below:
Low blood platelet count, blood in the stool, bruising at the injection site, accidental overdose of treatment,
increase in time for blood to clot, increase in the liver test value of alanine aminotransferase in the blood,
bleeding in between periods, and blood clot in the artery.
During the extension period, 6% (9 out of 144) of children reported side effects. The most common sideeffects which happened in at least 2 children were headache and nosebleed.
The other side effects only happened in only 1 child each during the extension period. These side effects arereported below:
Low blood platelet count, heart attack, blockage of blood flow to the heart muscle, common bruise, liver
injury, increase in liver test value of bilirubin, bruising under the skin, and bleeding from a broken bloodvessel.
DU176B-C-U313 Clinical Results Summary | 8How many children had to stop treatment because of side effects?

During the main treatment period, 1 child stopped edoxaban treatment due to blood clot in the artery.
During the extension period, 2 children stopped edoxaban treatment due to heart attack and blockage ofblood flow to the heart muscle.

How was this study useful for patients and researchers?
This study helped researchers learn about the safety and effects of edoxaban in the prevention of bloodvessels being blocked by clots in children with heart conditions.
Findings from this study may be used in other studies with edoxaban. Other studies for edoxaban are ongoing
and the sponsor plans to conduct more studies in the future.
Please remember, this summary only shows the results of a single study. Other studies may have different
findings. Please talk to a doctor before changing any treatment you are taking or if you have any questions
about these study results.

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Where can I learn more about this study?
You can find more information about this study on the following websites:www.clinicaltrials.gov: Use the NCT identifier NCT03395639 in the search field.
www.clinicaltrialsregister.eu/ctr-search/search: Use the EudraCT identifier 2017-000475-90 in
the search field.
Please remember that the results on these websites may be presented in a different way. If you were a study
child and have questions about the results of this study, please speak with the doctor or staff at your study
site.
Full study title: An Open-Label, Randomized,Parallel-Group, Multicenter, Observational Trial
to Evaluate the Safety and Efficacy of Edoxaban
Tosylate in Children from 38 Weeks Gestational
Age to Less than 18 Years of Age with Cardiac
Diseases at Risk of Thromboembolic Events.

Sponsor: Daiichi Sankyo, Inc.
Sponsor contact information:
211 Mount Airy Road, Basking Ridge, NJ 07920
Email: CTRInfo@dsi.com
Phone number: 1-908-992-6640
Date of this summary: 10 June 2022

This summary was prepared by Syneos Health.

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