Reversal of dabigatran anticoagulant effect with idarucizumab.

• Register: EUCTR
• Last refreshed on: 16 December 2019
• Main ID: EUCTR2015-002177-37-SE
• Date of registration: 18/03/2016
• Prospective Registration: Yes
• Primary sponsor: Boehringer Ingelheim AB
• Public title: Reversal of dabigatran anticoagulant effect with idarucizumab.
• Scientific title: Single dose, open label, uncontrolled, safety trial of intravenous administration of idarucizumab to paediatric patients enrolled from ongoing phase IIb/III clinical trials with dabigatran etexilate for the treatment and secondary prevention of venous thromboembolism.
• Date of first enrolment: 01/06/2016
• Target sample size: 10
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002177-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Bulgaria, Canada, Czech Republic, Finland, France, Germany, Greece, Italy, Lithuania, Norway, Russian Federation, Spain, Sweden, Switzerland, Turkey, United States

Contacts

• Name: QRPE PSC CT Information Disclosure
• Affiliation: Boehringer Ingelheim

• Name: QRPE PSC CT Information Disclosure
• Affiliation: Boehringer Ingelheim

Key inclusion & exclusion criteria

Inclusion criteria:
Patients taking dabigatran etexilate in the paediatric trials 1160.106 or 1160.108 are eligible for this trial if they meet the following criteria:

Group A:

- Overt bleeding judged by the treating physician to require a reversal agent.
- Currently taking dabigatran etexilate in the context of a clinical trial with dabigatran etexilate (1160.106 or 1160.108).
- Male or female patients from 0 to less than 18 years of age at the time of informed consent/assent for participation in trial 1160.106 or in trial 1160.108.
- Female patients of childbearing potential (defined as having experienced menarche) must have followed the contraception requirements according to the dabigatran trial 1160.106 or trial 1160.108 in which they are enrolled.
- Written informed consent provided by the patient (and/or the patient¿s legally accepted representative) and assent provided by the patient (if applicable) at the time of informed consent signature in accordance with GCP and local legislation prior to admission to the trial. If the child is unable to give assent at the time of the emergency, the assent, when applicable will be obtained as soon as feasible.

Group B:

- A condition requiring an emergency surgery or invasive procedure where adequate haemostasis is required. Emergency is defined as need for surgery or intervention within the following 8 hours.
- Currently taking dabigatran etexilate in the context of a clinical trial with dabigatran etexilate (1160.106 or 1160.108).
- Male or female patients from 0 to less than 18 years of age at the time of informed consent/assent for participation in trial 1160.106 or in trial 1160.108.
- Female patients of childbearing potential (defined as having experienced menarche) must have followed the contraception requirements according to the dabigatran trial 1160.106 or trial 1160.108 in which they are enrolled.
- Written informed consent provided by the patient (and/or the patient¿s legally accepted representative) and assent provided by the patient (if applicable) at the time of informed consent signature in accordance with GCP and local legislation prior to admission to the trial. If the child is unable to give assent at the time of the emergency, the assent, when applicable will be obtained as soon as feasible.




Are the trial subjects under 18? yes
Number of subjects for this age range: 9
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Group A:

- Patients with minor bleeding (e.g. epistaxis, haematuria) who can be managed with standard supportive care.
- Patients with no clinical signs of bleeding.
- Patients with body weight < 2.5 kg
- Contraindications to trial medication including known hypersensitivity to the drug or its excipients; i.e. patients with hereditary fructose intolerance who may react to sorbitol or infants with unknown hereditary fructose intolerance status.
- Female patients who are pregnant, nursing, or who plan to become pregnant while in the trial.

Group B:

- A surgery or procedure which is elective or where the risk of uncontrolled or unmanageable bleeding is low.
- Patients with body weight < 2.5 kg
- Contraindications to trial medication including known hypersensitivity to the drug or its excipients; i.e. patients with hereditary fructose intolerance who may react to sorbitol or infants with unknown hereditary fructose intolerance status.
- Female patients who are pregnant, nursing, or who plan to become pregnant while in the trial.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

MedDRA version: 18.1 Level: LLT Classification code 10066899 Term: Venous thromboembolism System Organ Class: 100000004866
MedDRA version: 18.1 Level: LLT Classification code 10049909 Term: Venous thromboembolism prophylaxis System Organ Class: 100000004865

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Trade Name: Praxbind
Product Name: idarucizumab
Product Code: BI 655075
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: IDARUCIZUMAB
Current Sponsor code: BI 655075
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 1: 30 days post-dose

Secondary Objective: Assessments of the reversal of dabigatran, bleeding status or emergency surgery/urgent procedures, clinical outcomes, pharmacokinetics of dabigatran and idarucizumab.

Primary end point(s): 1: Safety of idarucizumab in a paediatric population as assessed by the occurrence of drug-related adverse events (including immune reactions) and all-cause mortality during the trial.

Main Objective: To demonstrate the safety of idarucizumab, as assessed by the occurrence of patients with drug related adverse events (including immune reactions) and all-cause mortality in paediatric venous thromboembolism (VTE) patients treated with dabigatran in ongoing clinical trials who require emergency surgery/urgent procedures or patients who have life-threatening or uncontrolled bleeding which requires urgent intervention, when rapid reversal of the anticoagulant effects of dabigatran is needed.

Secondary Outcome(s)

Secondary end point(s): 1: Percent change of coagulation tests (dTT, ECT) at 30 minutes post-dose compared to pre-dose.

2: Time to achieve complete reversal of dabigatran effect, based on coagulation tests (dTT and ECT).

3: Duration of complete reversal of dabigatran effect sustained at 24 hours post-dose, based on coagulation tests (dTT and ECT).

4: Cessation of bleeding (Group A patients only).

5: Bleeding status and other clinical conditions that may contribute to bleeding (Group A patients only) during the trial.

6: Development of treatment-emergent ADA with cross reactivity to idarucizumab at
30 days post-dose of idarucizumab (binary).

Timepoint(s) of evaluation of this end point: 1: 30 minutes post-dose

2: Up to 24 hours post-dose

3: Up to 24 hours post-dose

4: Up to 24 hours post-dose

5: 30 days post-dose

6: 30 days post-dose

Secondary ID(s)

1321.7

Source(s) of Monetary Support

Boehringer Ingelheim AB

Ethics review

Status: Approved
Approval date:
Contact: