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

NCT ID: NCT05408546

Last Updated: 2023-07-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-05-24

Study Completion Date

2024-09-30

Brief Summary

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Phase II trial of TS23

Detailed Description

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

Conditions

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Pulmonary Embolism

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Placebo + standard of care (SOC) anticoagulation

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo

Low dose TS23

TS23 low dose + SOC anticoagulation

Group Type EXPERIMENTAL

TS23

Intervention Type DRUG

Monoclonal antibody to a2-antiplasmin

Intermediate dose TS23

TS23 medium dose + SOC anticoagulation

Group Type EXPERIMENTAL

TS23

Intervention Type DRUG

Monoclonal antibody to a2-antiplasmin

Higher dose TS23

TS23 highest dose + SOC anticoagulation

Group Type EXPERIMENTAL

TS23

Intervention Type DRUG

Monoclonal antibody to a2-antiplasmin

Interventions

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TS23

Monoclonal antibody to a2-antiplasmin

Intervention Type DRUG

Placebo

Placebo

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Translational Sciences, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Guy L Reed, MD

Role: PRINCIPAL_INVESTIGATOR

Translational Sciences

Locations

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Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Principal Investigator

Role: CONTACT

16177103979

Facility Contacts

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Susan Jackman, MSN

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 28028005 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31395599 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25256235 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24556477 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15842654 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25099590 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23521450 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25680885 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27090586 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33857326 (View on PubMed)

Other Identifiers

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TS23-U201

Identifier Type: -

Identifier Source: org_study_id

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