Novel α2-Antiplasmin Inactivation for Lysis of Intravascular Thrombi (NAIL-IT) Trial

Inclusion Criteria:

1. Male or female subjects, age >18 years;
2. PE involving a segmental or more proximal pulmonary artery confirmed by CTPA scan andwith 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 as indicated by a right ventricular-to-leftventricular (RV/LV) diameter ratio > 0.9 on CTPA scan (measuring the minor axis of theright and left ventricle in the transverse plane), prior to the initiation of studydrug administration.

Exclusion Criteria:

1. Subjects for whom thrombolytic therapy or thrombectomy is planned; or subjects withhistory of administration of thrombolytic agents within the previous 4 days;
2. Subjects receiving ≥ 48 hours of therapeutic doses of heparin or low molecular weightheparin (LMWH) or other anticoagulant therapy immediately prior to randomization;
3. Subjects with contraindications to SOC therapies such as unfractionated heparin orLMWH or oral anticoagulant, or any of the excipients (including study drugexcipients);
4. Subjects who are considered at very high risk of bleeding:
5. Known coagulation disorder with history of pathologic bleeding tendencies
6. Subjects with prior intracranial hemorrhage, known arteriovenous malformation oraneurysm of the brain, or evidence of active bleeding;
7. Subjects with a history of major surgery, clinically significant head trauma (inthe opinion of the Principal Investigator), or stroke in the past 3 months priorto randomization;
8. Subjects with uncontrolled hypertension defined as SBP ≥180 mm Hg and/ordiastolic BP (DBP) ≥110 mm Hg at randomization
9. Subjects requiring concomitant dual antiplatelet therapy
10. Subjects with Creatinine Clearance (CrCL) < 30 mL/min or serum creatinine ≥ 2.5 mg/dL;
11. Subjects with hemoglobin < 8.0 g/dL;
12. Subjects with a platelet count < 100,000/µL;
13. Subjects with acute or persistent hepatitis or diagnosed active liver disease or withelevation of liver enzymes: Alanine transaminase (ALT) or aspartate transaminase (AST) ≥ 3 x upper limit of normal (ULN);
14. Subjects with known history of testing positive for Hepatitis B antigen or Hepatitis Cantibody;
15. Subjects with known history of testing positive for the human immunodeficiency virus (HIV);
16. Subjects with life-expectancy < 6 months;
17. Female subjects of child bearing potential with a positive pregnancy test or who arelactating, or unwilling to use highly effective methods of contraception. Highlyeffective methods of birth control include combination hormonal therapy (estrogen andprogresterone), 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;
18. Subjects currently participating in another investigational study or who haveparticipated in an investigational drug study within 30 days (or longer depending onthe half-life of the investigational drug; should allow at least five half-life of theinvestigational drug) prior to randomization.