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

NCT05408546 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: TS23-U201
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Phase II trial of TS23

Conditions

Pulmonary Embolism

Outcome Measures

Primary Outcomes (2)

• RV/LV

  Ratio of the right to left ventricle dimensions on CT perfusion angiogram (CTPA)

  48 hours after treatment

• Safety- Bleeding

  Frequency of major or clinically significant bleeding

  within 7 days of treatment

Secondary Outcomes (1)

• Thrombus dissolution

  48 hours after treatment

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo + standard of care (SOC) anticoagulation

Drug: Placebo

Low dose TS23

EXPERIMENTAL

TS23 low dose + SOC anticoagulation

Drug: TS23

Intermediate dose TS23

EXPERIMENTAL

TS23 medium dose + SOC anticoagulation

Drug: TS23

Higher dose TS23

EXPERIMENTAL

TS23 highest dose + SOC anticoagulation

Drug: TS23

Interventions

TS23 DRUG

Monoclonal antibody to a2-antiplasmin

Higher dose TS23; Intermediate dose TS23; Low dose TS23

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects, age \>18 years;
• 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;
• Subject is hemodynamically stable with a systolic blood pressure (SBP) \>90 mm Hg;
• 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.

You may not qualify if:

• Subjects for whom thrombolytic therapy or thrombectomy is planned; or subjects with history of administration of thrombolytic agents within the previous 4 days;
• Subjects receiving ≥ 48 hours of therapeutic doses of heparin or low molecular weight heparin (LMWH) or other anticoagulant therapy immediately prior to randomization;
• Subjects with contraindications to SOC therapies such as unfractionated heparin or LMWH or oral anticoagulant, or any of the excipients (including study drug excipients);
• Subjects who are considered at very high risk of bleeding:
• Known coagulation disorder with history of pathologic bleeding tendencies
• Subjects with prior intracranial hemorrhage, known arteriovenous malformation or aneurysm of the brain, or evidence of active bleeding;
• 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;
• Subjects with uncontrolled hypertension defined as SBP ≥180 mm Hg and/or diastolic BP (DBP)
• ≥110 mm Hg at randomization
• Subjects requiring concomitant dual antiplatelet therapy
• Subjects with Creatinine Clearance (CrCL) \< 30 mL/min or serum creatinine ≥ 2.5 mg/dL;
• Subjects with hemoglobin \< 8.0 g/dL;
• Subjects with a platelet count \< 100,000/µL;
• 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);
• Subjects with known history of testing positive for Hepatitis B antigen or Hepatitis C antibody;

Sponsors & Collaborators

• Translational Sciences, Inc.: lead

Study Sites (1)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

Related Publications (10)

• 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.

  PMID: 28028005 BACKGROUND

• 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.

  PMID: 31395599 BACKGROUND

• 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.

  PMID: 25256235 BACKGROUND

• 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.

  PMID: 24556477 BACKGROUND

• 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.

  PMID: 15842654 BACKGROUND

• 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.

  PMID: 25099590 BACKGROUND

• 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.

  PMID: 23521450 BACKGROUND

• 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.

  PMID: 25680885 BACKGROUND

• 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.

  PMID: 27090586 BACKGROUND

• 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.

  PMID: 33857326 BACKGROUND

MeSH Terms

Conditions

Pulmonary Embolism

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Embolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Guy L Reed, MD

  Translational Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Principal Investigator

CONTACT

16177103979; glreed@translationalsciences.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2022
• First Posted: June 7, 2022
• Study Start: May 24, 2023
• Primary Completion: July 1, 2024
• Study Completion: September 1, 2024
• Last Updated: July 11, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)