A Phase 3, Open-Label, Study to Evaluate Pharmacokinetics and Pharmacodynamics of Edoxaban and to compare the safety and efficacy of Edoxaban with standard of care treatment in Paediatric Patients confirmed as requiring treatment for a blood clot

Phase 1

• Conditions: venous thromboembolism; MedDRA version: 21.1Level: LLTClassification code 10066899Term: Venous thromboembolismSystem Organ Class: 100000004866; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2016-000991-49-NO
• Lead Sponsor: Daiichi Sankyo, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-10-31
• Last Update Posted: 8 August 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 274

Inclusion Criteria

Subjects must satisfy all of the following criteria to be included in the study:

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

2. Pediatric subjects with the presence of documented VTE confirmed by appropriate diagnostic imaging and requiring anticoagulant therapy for at least 90 days.
-Subjects <6 months old (Cohort 5) with the presence of documented VTE confirmed by appropriate diagnostic imaging and requiring anticoagulant therapy for at least 6 to 12 weeks.
3. Subjects must have received at least 5 days of heparin (LMWH or SP Xa inhibitors or UFH according to the edoxaban label for VTE treatment) therapy prior to randomization to treat the newly identified index VTE. In addition, prior to being randomized to edoxaban or SOC, subjects initially treated with VKA are recommended to have an INR = 2.5.

4. Subject and/or parent(s)/legal guardian(s) or legally acceptable representative is informed and provides signed consent for the child to participate in the study with edoxaban treatment. Pediatric subjects with appropriate intellectual maturity will be required to sign an assent form in addition to the signed informed consent from the parent(s)/legal guardian(s) or any legally acceptable representative.

5. Female subjects who have menarche must test negative for pregnancy at Screening and must consent to avoid becoming pregnant by using an approved contraception method throughout the study.
Are the trial subjects under 18? yes
Number of subjects for this age range: 274
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects who meet any of the following criteria will be disqualified from entering the
study:
1. Subjects with active bleeding or high risk of bleeding contraindicating treatment with LMWH, SP Xa inhibitors, VKAs, or direct oral anticoagulants (DOACs; identified high risk of bleeding during prior experimental administration of DOACs).

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

3. Administration of antiplatelet therapy is contraindicated in both arms except for low 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 on concomitant use of rifampin are excluded.

5a. Subjects with severe hepatic impairment or hepatic disease associated with coagulopathy (eg acute hepatitis, chronic active hepatitis, and cirrhosis).
b) Subjects with ALT > 5 × the upper limit of normal (ULN) or total bilirubin >2 × ULN with direct bilirubin > 20% of the total at Screening.
c) Subjects with aPTT >50 seconds or international
normalized ratio [INR] >2.0 not related to
anticoagulation therapy.

6. Subjects with estimated glomerular filtration rate (GFR) < 30% of normal for age and size

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

8. Subject with thrombocytopenia < 50 × 109/L at Screening Visit. Subjects with a history of heparin-induced thrombocytopenia may be enrolled in the study at the Investigator’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 the subject at increased risk of harm if he/she participated in the study including contraindicated medications identified in Appendix 17.4

12. Subjects who participated in another interventional clinical study or were treated with an experimental therapy with less than a 30-day wash-out period prior to identifying the qualifying index VTE.

13. Hypersensitivity to the active ingredient or to any of the excipients of any components of the trial treatment.

14. Patients with a history of thrombosis who are diagnosed with antiphospholipid syndrome who are triple positive (for lupus anticoagulant, anticardiolipin antibodies, and anti-beta 2-glycoprotein I antibodies).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified