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

Pulmonary Embolism Clinical Trial

— NAIL-IT  

Official title:

Evaluation of the Safety and Thrombolytic Effects of Ascending Doses of TS23 in Subjects With Intermediate-Risk (Sub-Massive) Acute Pulmonary Embolism

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05408546
• Other study ID #: TS23-U201
• Status: Recruiting
• Phase: Phase 2
• Start date: May 24, 2023
• Est. completion date: September 2024

Study information

• Verified date: July 2023
• Source: Translational Sciences, Inc.
• Contact: Principal Investigator
• Phone: 16177103979
• Email: glreed[@]translationalsciences.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Phase II trial of TS23

Description:

Evaluation of safety and thrombolytic effect of ascending doses of TS23 in subjects with intermediate-risk (sub-massive) acute pulmonary embolism (PE)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: September 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 as indicated by a 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), prior to the initiation of study drug administration.

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 low molecular weight heparin (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:

1. Known coagulation disorder with history of pathologic bleeding tendencies

2. Subjects with prior intracranial hemorrhage, known arteriovenous malformation or aneurysm of the brain, or evidence of active bleeding;

3. 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;

4. Subjects with uncontrolled hypertension defined as SBP =180 mm Hg and/or diastolic BP (DBP)

=110 mm Hg at randomization

5. 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.

Related Conditions & MeSH terms

• Embolism
• Pulmonary Embolism

Intervention

Drug:
• TS23
Monoclonal antibody to a2-antiplasmin
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Cedars Sinai Medical Center	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Translational Sciences, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (10)

Aghayev A, Furlan A, Patil A, Gumus S, Jeon KN, Park B, Bae KT. The rate of resolution of clot burden measured by pulmonary CT angiography in patients with acute pulmonary embolism. AJR Am J Roentgenol. 2013 Apr;200(4):791-7. doi: 10.2214/AJR.12.8624. — View Citation

Cesarman-Maus G, Hajjar KA. Molecular mechanisms of fibrinolysis. Br J Haematol. 2005 May;129(3):307-21. doi: 10.1111/j.1365-2141.2005.05444.x. — View Citation

Houng AK, Wang D, Reed GL. Reversing the deleterious effects of alpha2-antiplasmin on tissue plasminogen activator therapy improves outcomes in experimental ischemic stroke. Exp Neurol. 2014 May;255:56-62. doi: 10.1016/j.expneurol.2014.02.009. Epub 2014 Feb 18. — View Citation

Meinel FG, Nance JW Jr, Schoepf UJ, Hoffmann VS, Thierfelder KM, Costello P, Goldhaber SZ, Bamberg F. Predictive Value of Computed Tomography in Acute Pulmonary Embolism: Systematic Review and Meta-analysis. Am J Med. 2015 Jul;128(7):747-59.e2. doi: 10.1016/j.amjmed.2015.01.023. Epub 2015 Feb 11. — View Citation

Meyer G, Vicaut E, Konstantinides SV. Fibrinolysis for intermediate-risk pulmonary embolism. N Engl J Med. 2014 Aug 7;371(6):581-2. doi: 10.1056/NEJMc1406283. No abstract available. — View Citation

Ouriel K, Ouriel RL, Lim YJ, Piazza G, Goldhaber SZ. Computed tomography angiography with pulmonary artery thrombus burden and right-to-left ventricular diameter ratio after pulmonary embolism. Vascular. 2017 Feb;25(1):54-62. doi: 10.1177/1708538116645056. Epub 2016 Jul 9. — View Citation

Reed GL, Houng AK, Wang D. Microvascular thrombosis, fibrinolysis, ischemic injury, and death after cerebral thromboembolism are affected by levels of circulating alpha2-antiplasmin. Arterioscler Thromb Vasc Biol. 2014 Dec;34(12):2586-93. doi: 10.1161/ATVBAHA.114.304530. Epub 2014 Sep 25. — View Citation

Singh S, Houng A, Reed GL. Releasing the Brakes on the Fibrinolytic System in Pulmonary Emboli: Unique Effects of Plasminogen Activation and alpha2-Antiplasmin Inactivation. Circulation. 2017 Mar 14;135(11):1011-1020. doi: 10.1161/CIRCULATIONAHA.116.024421. Epub 2016 Dec 27. — View Citation

Singh S, Houng AK, Reed GL. Venous stasis-induced fibrinolysis prevents thrombosis in mice: role of alpha2-antiplasmin. Blood. 2019 Sep 19;134(12):970-978. doi: 10.1182/blood.2019000049. Epub 2019 Aug 8. — View Citation

Zuo Z, Yue J, Dong BR, Wu T, Liu GJ, Hao Q. Thrombolytic therapy for pulmonary embolism. Cochrane Database Syst Rev. 2021 Apr 15;4(4):CD004437. doi: 10.1002/14651858.CD004437.pub6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	RV/LV	Ratio of the right to left ventricle dimensions on CT perfusion angiogram (CTPA)	48 hours after treatment
Primary	Safety- Bleeding	Frequency of major or clinically significant bleeding	within 7 days of treatment
Secondary	Thrombus dissolution	Change in modified Miller Score	48 hours after treatment