Hokusai Study in Pediatric Patients With Confirmed Venous Thromboembolism (VTE)

Inclusion Criteria:

1. Male or female pediatric subjects between birth (defined as 38 weeks gestationalage) and less than 18 years of age at the time of consent.

2. Pediatric subjects with the presence of documented VTE confirmed by appropriatediagnostic imaging and requiring anticoagulant therapy for at least 90 days.

3. Subjects must have received at least 5 days of heparin therapy prior torandomization to treat the newly identified index VTE. In addition, prior to beingrandomized to edoxaban or SOC, subjects initially treated with VKA are recommendedto have an international normalized ratio (INR) < 2.0.

4. Subject and/or parent(s)/legal guardian(s) or legally acceptable representative isinformed and provides signed consent for the child to participate in the study.

5. Female subjects who have menarche must test negative for pregnancy at Screening andmust consent to avoid becoming pregnant by using an approved contraception methodthroughout the study.

Exclusion Criteria:

1. Subjects with active bleeding or high risk of bleeding contraindicating treatmentwith LMWH, SP Xa inhibitors, VKAs, or direct oral anticoagulants (DOACs; identifiedhigh risk of bleeding during prior experimental administration of DOACs).

2. Subjects who have been or are being treated with thrombolytic agents, thrombectomyor insertion of a caval filter for the newly identified index VTE.

3. Administration of antiplatelet therapy is contraindicated in both arms except forlow dose aspirin defined as 1-5 mg/Kg/day with maximum of 100 mg/day.

4. Administration of rifampin is prohibited during the study and subjects onconcomitant use of rifampin are excluded.

5. Subjects with hepatic disease associated with coagulopathy leading to a clinicallyrelevant bleeding risk (aPTT > 50 seconds or international normalized ratio [INR] > 2.0 not related to anticoagulation therapy) or alanine aminotransferase (ALT) > 5 ×the upper limit of normal (ULN) or total bilirubin > 2 × ULN with direct bilirubin > 20% of the total at Screening Visit.

6. Subjects with glomerular filtration rate (GFR) < 30% of normal for age and size asdetermined by the Schwartz formula.

7. Subjects with stage 2 hypertension defined as blood pressure (BP) systolic and/ordiastolic confirmed > 99th percentile + 5 mmHg.

8. Subject with thrombocytopenia < 50 × 109/L at Screening Visit. Subjects with ahistory of heparin-induced thrombocytopenia may be enrolled in the study at theInvestigator's discretion.

9. Life expectancy less than the expected study treatment duration (3 months).

10. Subjects who are known to be pregnant or breastfeeding.

11. Subjects with any condition that, as judged by the Investigator, would place thesubject at increased risk of harm if he/she participated in the study, includingcontraindicated medications.

12. Subjects who participated in another clinical study or treated with an experimentaltherapy with less than a 30 day washout period prior to identifying the qualifyingindex VTE.