Clinical Trials List
Protocol NumberDU176b-D-U312
NCT Number(ClinicalTrials.gov Identfier)無
2018-03-01 - 2022-08-31
Phase III
Recruiting5
ICD-10I82
Other venous embolism and thrombosis
A PHASE 3, OPEN-LABEL, RANDOMIZED, MULTICENTER, CONTROLLED TRIAL TO EVALUATE THE PHARMACOKINETICS AND PHARMACODYNAMICS OF EDOXABAN AND TO COMPARE THE EFFICACY AND SAFETY OF EDOXABAN WITH STANDARD OF CARE ANTICOAGULANT THERAPY IN PEDIATRIC SUBJECTS FROM BIRTH TO LESS THAN 18 YEARS OF AGE WITH CONFIRMED VENOUS THROMBOEMBOLISM (VTE)
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Trial Applicant
IQVIA RDS Taiwan Ltd.
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Sponsor
-
Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 巫康熙 無
- 張正成 無
- Yun-Ching Fu 無
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
Venous thromboembolism
Objectives
Primary Objective:
The primary objective is to demonstrate the non-inferiority of
edoxaban to standard of care (SOC; including low molecular
weight heparin (LMWH), vitamin K antagonist (VKA), or
synthetic pentasaccharide (SP) Xa inhibitors) in the treatment
and secondary prevention of VTE in pediatric subjects with
regard to the composite efficacy endpoint (ie, symptomatic
recurrent VTE, death as result of VTE, and no change or
extension of thrombotic burden) during the first 3-month
treatment period.
Secondary Objectives:
To compare edoxaban against SOC with regard to the
combination of major and clinically relevant nonmajor (CRNM) bleedings occurring during treatment
or within 3 days of completing or interrupting or
stopping study treatment during the first 3-month
treatment period.
To compare edoxaban against SOC with regard to a
combination of major and CRNM bleedings and
symptomatic recurrent VTE, and death as result of
VTE which occur from first to the last dose + 30
days.
To compare edoxaban against SOC with regard to all
bleedings which occur from first to the last dose + 30
days.
To compare edoxaban against SOC with regard to the
composite efficacy endpoint as described in the
primary objective from randomization to the last
dose + 30 days.
To compare edoxaban against SOC with regard to
all-cause mortality from randomization to the last
dose + 30 days.
To compare edoxaban against SOC with regard to the
individual components of the composite efficacy
endpoints as described in the primary objective
during the first 3-month treatment period.
To compare edoxaban against SOC with regard to
occurrence of DVT, catheter-related thrombosis, PE,
sinovenous thrombosis within and after the first 3-
month treatment period.
To compare edoxaban against SOC with regard to a
composite combination of major and CRNM
bleedings from first to the last dose + 30 days.
To characterize the multiple dose pharmacokinetics
of edoxaban in pediatric subjects at Day 5 using
population pharmacokinetic (PK) analysis (apparent
systemic clearance [CL/F] and apparent volume of
distribution [V/F]) and to assess the effect of
covariates such as age, body weight, and renal
function on the PK of edoxaban.
To evaluate the relationship between edoxaban
exposure and safety (such as bleeding) and efficacy
(thromboembolic events).
To characterize the effect of edoxaban on biomarkers
of coagulation (ie, prothrombin time [PT], activated
partial thromboplastin time [aPTT], and antiactivated factor X [anti-FXa])
Test Drug
Edoxaban
Active Ingredient
Edoxaban
Dosage Form
tablet
Dosage
15mg, 30mg, 60 mg
Endpoints
Primary Efficacy Endpoint:
The primary efficacy endpoint is a composite endpoint
consisting of the incidence of symptomatic recurrent venous
thromboembolic disease, death as a result of VTE, and no
change or extension of thrombotic burden (Section 7.1) during
the first 3 months period.
Secondary Efficacy Endpoints:
The secondary efficacy endpoints include:
A composite endpoint consisting of symptomatic
recurrent venous thromboembolic disease, death as a
result of VTE, and no change or extension of
thrombotic burden from randomization to the date of
the last dose of study drug + 30 days .
The individual components of the primary efficacy
endpoint during the first 3-month period:
Symptomatic recurrent VTE
Death as a result of VTE
No change or extension of thrombotic burden
All-cause mortality from randomization to last dose
+ 30 days.
The DVT, Catheter-related thrombosis, PE,
sinovenous thrombosis events within and after the
first 3-month treatment period.
Net Clinical Outcome Endpoint:
Composite of symptomatic recurrent VTE events,
death as a result of VTE, and major and CRNM
bleeding that occurred from the date of the first dose
of study drug to the date of last dose of study drug +
30 days.
Safety Endpoints:
The safety endpoints are:
A combination of major and CRNM bleedings
occurring during treatment or within 3 days of
completing or interrupting or stopping study during
the first 3-month treatment period.
All bleedings from first to the last dose + 30 days.
A combination of major and CRNM bleedings from
first to the last dose + 30 days.
The primary efficacy endpoint is a composite endpoint
consisting of the incidence of symptomatic recurrent venous
thromboembolic disease, death as a result of VTE, and no
change or extension of thrombotic burden (Section 7.1) during
the first 3 months period.
Secondary Efficacy Endpoints:
The secondary efficacy endpoints include:
A composite endpoint consisting of symptomatic
recurrent venous thromboembolic disease, death as a
result of VTE, and no change or extension of
thrombotic burden from randomization to the date of
the last dose of study drug + 30 days .
The individual components of the primary efficacy
endpoint during the first 3-month period:
Symptomatic recurrent VTE
Death as a result of VTE
No change or extension of thrombotic burden
All-cause mortality from randomization to last dose
+ 30 days.
The DVT, Catheter-related thrombosis, PE,
sinovenous thrombosis events within and after the
first 3-month treatment period.
Net Clinical Outcome Endpoint:
Composite of symptomatic recurrent VTE events,
death as a result of VTE, and major and CRNM
bleeding that occurred from the date of the first dose
of study drug to the date of last dose of study drug +
30 days.
Safety Endpoints:
The safety endpoints are:
A combination of major and CRNM bleedings
occurring during treatment or within 3 days of
completing or interrupting or stopping study during
the first 3-month treatment period.
All bleedings from first to the last dose + 30 days.
A combination of major and CRNM bleedings from
first to the last dose + 30 days.
Inclution Criteria
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.
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 .
2. Pediatric subjects with the presence of documented VTE confirmed by appropriate diagnostic imaging and requiring anticoagulant therapy for at least 90 days.
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 .
Exclusion Criteria
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.
5. a) 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 (eGFR) <30% of normal for age and size (see Appendix 17.7).
7. Subjects with stage 2 hypertension defined as blood pressure (BP) systolic and/or diastolic confirmed >99th percentile + 5 mmHg (see Appendix 17.8).
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).
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.
5. a) 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 (eGFR) <30% of normal for age and size (see Appendix 17.7).
7. Subjects with stage 2 hypertension defined as blood pressure (BP) systolic and/or diastolic confirmed >99th percentile + 5 mmHg (see Appendix 17.8).
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).
The Estimated Number of Participants
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Taiwan
8 participants
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Global
274 participants
