Study to evaluate the safety and thrombolytic effect of increasing doses of DS9231 in sujbects with severe pulmonary embolism

Phase 1

• Conditions: DS9231, also known as TS23, is an inhibitor of alpha2-antiplasmin, incrasing plasmin acitivy and enhances fibrinolysis (thrombolysis) and intended to be used for the treatment of patients with Intermediate-Risk (Sub-Massive) Acute Pulmonary Embolism (PE).; MedDRA version: 20.0Level: HLTClassification code 10037379Term: Pulmonary embolism and thrombosisSystem Organ Class: 100000004866; MedDRA version: 20.0Level: PTClassification code 10037377Term: Pulmonary embolismSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2017-000552-25-HU
• Lead Sponsor: Daiichi Sankyo Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-05-31
• Last Update Posted: 11 December 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 104

Inclusion Criteria

1. Male or female subjects, age >18 years;
2. PE involving a segmental or more proximal pulmonary artery confirmed by CTPA scan and with an onset of symptoms not more than 5 days prior to diagnosis;
3. Subject is hemodynamically stable with a systolic blood pressure (SBP) >90 mm Hg
4. Subject has evidence of RV dysfunction (at least one of the following):
• Right ventricular-to-left ventricular (RV/LV) diameter ratio > 0.9 on CTPA scan (measuring the minor axis of the right and left ventricle in the transverse plane),
• or myocardial injury as evidenced by an elevated cardiac Troponin T or Troponin I (using the test of the local laboratory of Clinical Chemistry at the participating site). An abnormal value is that above the 99th percentile of the healthy population as a cutoff using an assay with acceptable precision. The 99th percentile cutoff point for cardiac Troponin T (cTnT) is well-known at 0.01 ng/mL as only one cTnT assay exists. In contrast, several different assays are commercially available for cardiac Troponin I (cTnI), so the 99th percentile cut point varies based on the assay being used. Please refer to Appendix 17.3 as guideline for acceptable abnormal Troponin I values.
• or RV/LV ratio > 0.9 on echocardiogram (apical or subcostal 4 - chamber view echocardiogram). A trained cardiac sonographer may not be available during non-business hours (for emergency admissions); however, if feasible, obtain echocardiogram prior to the initiation of study drug administration.
Eligible subjects, who qualify and have executed informed consent, will be randomized as early as possible and every effort will be made to administer the study medication (DS-9231 versus placebo) as soon as possible within the first 6 hours after the randomization

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 52
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 52

Exclusion Criteria

1. Subjects for whom thrombolytic therapy or thrombectomy is planned; or subjects with history of administration of thrombolytic agents within the previous 4 days;
2. Subjects receiving = 48 hours of therapeutic doses of heparin or LMWH or other anticoagulant therapy immediately prior to randomization;
3. Subjects with contraindications to SOC therapies such as unfractionated heparin or LMWH or oral anticoagulant, or any of the excipients (including study drug excipients);
4. Subjects who are considered at very high risk of bleeding:
a. Known coagulation disorder with history of pathologic bleeding tendencies
b. Subjects with prior intracranial hemorrhage, known arteriovenous malformation or aneurysm of the
brain, or evidence of active bleeding;
c. Subjects with a history of major surgery, clinically significant head trauma (in the opinion of the
Principal Investigator), or stroke in the past 3 months prior to randomization;
d. Subjects with uncontrolled hypertension defined as SBP =180 mm Hg and/or diastolic BP
(DBP) =110 mm Hg at randomization
e. Subjects requiring concomitant dual antiplatelet therapy
5. Subjects with Creatinine Clearance (CrCL) < 30 mL/min or serum creatinine = 2.5 mg/dL;
6. Subjects with hemoglobin < 8.0 g/dL;
7. Subjects with a platelet count < 100,000/µL;
8. Subjects with acute or persistent hepatitis or diagnosed active liver disease or with elevation of liver enzymes: Alanine transaminase (ALT) or aspartate transaminase (AST) = 3 x upper limit of normal (ULN);
9. Subjects with known history of testing positive for Hepatitis B antigen or Hepatitis C antibody;
10. Subjects with known history of testing positive for the human immunodeficiency virus (HIV);
11. Subjects with life-expectancy < 6 months;
12. Female subjects of child bearing potential with a positive pregnancy test or who are lactating, or unwilling to use highly effective methods of contraception. Highly effective methods of birth control include combination hormonal therapy (estrogen and progresterone), contraceptives administered orally, intravaginally or transdermally, progesterone-only contraceptives administered orally, by injection or implantation, use of an intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, partner vasectomy or sexual abstinence;
13. Subjects currently participating in another investigational study or who have participated in an investigational drug study within 30 days (or longer depending on the half-life of the investigational drug; should allow at least five half-life of the investigational drug) prior to randomization.

Study & Design

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