A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Single Ascending Dose Study to Assess the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of DS-1040b when Added to Standard of Care Anticoagulation Therapy in Subjects with Acute<br>Submassive Pulmonary Embolism.

Completed

• Conditions: Pulmonary embolism; 10014523

• Registration Number: NL-OMON47535
• Lead Sponsor: Daiichi Sankyo, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 2020-03-13
• Last Update Posted: 28 February 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 22

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

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 < 90 mmHg for more than 15 consecutive minutes or a drop in 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 < 100,000, international normalized ratio (INR) > 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 < 6 month history of acute coronary syndrome (ACS) whether or not they have undergone percutaneous coronary intervention (PCI);
10. Subjects who require ongoing dual antiplatelet therapy or treatment with aspirin alone in a dosage of more than 100 mg/per day;
11. Chronic treatment with non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) including both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) inhibitors for >= 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 < 10 g/dL;
18. Subjects with an estimated creatinine clearance < 60 mL/min;
19. Subjects with diagnosed active liver disease or with elevation of liver enzymes/bilirubin:
a. Alanine transaminase (ALT) or aspartate transaminase (AST) >= 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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Objective: To assess the safety and tolerability of ascending doses of<br /><br>DS-1040b given as a single intravenous (IV) infusion over 12, 24, 48 and 72<br /><br>hours (h), respectively, when added to standard of care (SOC) anticoagulation<br /><br>therapy compared to placebo by evaluating the rate of adjudicated clinically<br /><br>relevant bleeding (International Society of Thrombosis and Haemostasis (ISTH)<br /><br>major or clinically relevant nonmajor<br /><br>(CRNM) bleeding).</p><br>