Pulmonary embolism
Conditions
Interventions
All patients will receive Enoxaparin 1mg/kg for 3-6 days (depending on the
Cohort) and anticoagulant (chosen by the investigator) starting from the end of
the IP infusion until Day 30.
Sponsors
Daiichi Sankyo, Inc
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male or female subjects, age 18 to 75 years and body weight between 50 and 130 kg, inclusive; 2. Subjects admitted to the hospital with a clinical diagnosis of acute PE with an onset of symptoms in the 5 days prior to diagnosis categorized as low risk or intermediate-risk or submassive PE and for whom catheter-based therapy is not planned; a. Subjects must have a CTA scan confirming the PE diagnosis and with at least one measurable index lesion in a segmental or larger pulmonary artery prior to randomization; b. Subjects should be in otherwise satisfactory health in the opinion of the Investigator; c. Subjects may have concurrent DVT and have an inferior vena cava (IVC) filter placed prior to randomization; d. Subjects may already be on SOC low molecular weight (Heparin) [LMW (Heparin)] at the time of randomization but for no longer than 36 hours. 3. Able to provide written informed consent.
Exclusion criteria
Exclusion criteria: 1. Subjects with acute PE categorized as high-risk or massive, or who are hemodynamically unstable, evidenced by a heart rate > 120 /min and a systolic blood pressure (SBP) of 40 mmHg since presentation; 2. Subjects for whom use of a thrombolytic, either systemic or via catheter, is planned; 3. Subjects with PE lesions only in the sub-segmental or smaller arteries, which due to limitations of the imaging method may not be consistently identified and measured; 4. Subjects unable or unwilling to take the required SOC anticoagulation therapy; 5. Subjects receiving more than 36 hours of SOC anticoagulants (eg, unfractionated heparin, LMW heparin, Vitamin K antagonists or novel oral anticoagulants) for treatment of the index PE event prior to randomization. Study drug infusion will ideally begin within 6 hours after randomization; 6. Subjects who had prior intracranial hemorrhage, known arteriovenous malformation or aneurysm, or evidence of active bleeding; 7. Subjects with bleeding diathesis, a platelet count 1.7, or a clinically significant elevated activated partial thromboplastin time (aPTT) that is not explained by use of LMWH; 8. Subjects with active endocarditis; 9. Subjects with = 4 days/week anticipated to continue during the study; 12. Subjects with uncontrolled hypertension at randomization, evidenced by SBP > 180 mm Hg or diastolic blood pressure>120 mmHg, or who require parenteral medication to maintain blood pressure below these limits; 13. Subjects who within 3 months prior to randomization have had intracranial surgery, clinically significant head trauma (in the opinion of the Principal Investigator), a stroke, or have received thrombolytic treatment; 14. Subjects with ECG evidence of 2 nd degree or higher atrioventricular (AV) block or with QTcB or QTcF> 450 ms; 15. Subjects who within 21 days prior to randomization have had gastrointestinal or genitourinary bleeding; 16. Subjects who within 14 days prior to randomization have had major surgery or a lumbar puncture (or epidural steroid injection); 17. Subjects with hemoglobin = 2 times upper limit of normal (ULN) b. Total bilirubin (TBL) >= 1.5 times ULN (except due to confirmed Gilbert*s syndrome) 20. Subjects with known history of testing positive for Hepatitis B antigen or Hepatitis C antibody before randomization; 21. Subjects with known history of testing positive for the human immunodeficiency virus (HIV); 22. Subjects with active cancer defined as recurrent, regionally advanced, metastatic disease, or a hematologic malignancy not in complete remission and subjects with malignancy diagnosed
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Objective: To assess the safety and tolerability of ascending doses of DS-1040b given as a single intravenous (IV) infusion over 12, 24, 48 and 72 hours (h), respectively, when added to standard of care (SOC) anticoagulation therapy compared to placebo by evaluating the rate of adjudicated clinically relevant bleeding (International Society of Thrombosis and Haemostasis (ISTH) major or clinically relevant nonmajor (CRNM) bleeding). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Objectives: To assess the following efficacy endpoints as evaluation of proof-of-concept: 1. Relative reduction (% reduction) in total thrombus volume from baseline to = 20% greater relative reduction in total thrombus volume assessed by CTA in segmental or larger pulmonary arteries, from baseline to = 50% greater relative reduction in total thrombus volume assessed by CTA in segmental or larger pulmonary arteries, from baseline to | — |
Countries
Netherlands
Outcome results
None listed