Tenecteplase in Stroke Patients Between 4.5 and 24 Hours

NCT03785678 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: ML40787
• Study Type: interventional
• Target: 458
• Locations: 2 countries
• Sites: 97

Brief Summary

This study will evaluate the efficacy and safety of tenecteplase compared with placebo in participants with acute ischemic stroke (AIS). All participants will receive standard-of-care therapy according to AmericanHeart Association/American Stroke Association clinical guidelines (2018). To determine eligibility for randomization, all participants will undergo multimodal CT or MRI at baseline. Only participants with a vessel occlusion (ICA or MCA M1/M2) and penumbral tissue will be randomized. The primary analysis is to compare the efficacy of tenecteplase versus placebo in all participants at Day 90.

Conditions

THROMBOLYSIS

Outcome Measures

Primary Outcomes (1)

• Ordinal Modified Rankin Scale (mRS) Score at Day 90

  The the modified Rankin score (mRS) is a 6-point scale commonly used to assess disability due to stroke, with higher values indicating worse outcomes. 0 = No symptoms 1. = No significant disability 2. = Slight disability 3. = Moderate disability 4. = Moderately severe disability 5. = Severe disability 6. = Death

  Day 90

Secondary Outcomes (10)

• Proportion of Patients With Functional Independence at Day 90

  Day 90

• Proportion of Patients With Recanalization at 24 Hours Post-randomization

  Day 2

• Proportion of Patients With Reperfusion at 24 Hours Post-randomization

  Day 2

• Proportion of Patients With Angiographic Reperfusion at Completion of Angiographic Procedure

  Day 1

• Median NIHSS Score at Day 90

  Day 90

Study Arms (2)

Tenecteplase

EXPERIMENTAL

Patients in this arm will receive Tenecteplase (0.25 mg/kg, maximum 25 mg) administered as a single bolus injection over 5 seconds.

Biological: Tenecteplase

Placebo

PLACEBO COMPARATOR

Patients in this arm will receive placebo administered as a single bolus injection over 5 seconds.

Other: Placebo

Interventions

Tenecteplase BIOLOGICAL

The investigational medicinal product (IMP) for this study is tenecteplase. The recommended total dose for this study is weight-based with 0.25 mg of tenecteplase per kg, not exceeding a maximum dose of 25 mg. A single bolus dose should be administered over 5 seconds based on patient weight.

Tenecteplase

Placebo OTHER

Placebo is being used as the comparator since a thrombolytic is only FDA-approved in the United States for use out to 3 hours, and the standard of care guidelines support use out to 4.5 hours.

Placebo

Eligibility Criteria

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

You may qualify if:

• Patient/legally authorized representative has signed the Informed Consent Form
• Age \>= 18 years
• AIS symptom onset within 4.5 to 24 hours Signs and symptoms consistent with the diagnosis of an acute anterior circulation ischemic stroke involving occlusion of the ICA, M1, or M2 vessels
• Functionally independent (mRS 0-2) prior to stroke onset
• Baseline NIHSS \>=5 and that remains \>=5 immediately prior to randomization
• Neuroimaging: ICA or M1, M2 occlusion (carotid occlusions can be cervical or intracranial, with or without tandem MCA lesions) by magnetic resonance angiography (MRA) or computed tomography angiography (CTA) AND target mismatch profile on CT perfusion or MR perfusion (ischemic core volume \<70 mL, mismatch ratio is \>=1.8 and mismatch volume is \>= 15 mL)
• The mismatch volume is determined by FDA-approved imaging software in real time based on the difference between the ischemic core lesion volume and the Tmax\>6s lesion volume. If both a CT perfusion and a multimodal MRI scan are performed prior to enrollment, the later of the 2 scans is assessed to determine eligibility. Only an intracranial MRA is required for patients screened with MRA; cervical MRA is not required. Cervical and intracranial CTA are typically obtained simultaneously in patients screened with CTA, but only the intracranial CTA is required for enrollment.
• Alternative neuroimaging:
• If CTA (or MRA) is technically inadequate: Tmax\>6s perfusion deficit consistent with an ICA or M1, M2 occlusion AND target mismatch profile (ischemic core volume \<70 mL, mismatch ratio \>= 1.8 and mismatch volume \>= 15 mL as determined by RAPID software)
• If magnetic resonance perfusion (MRP) is technically inadequate: ICA or M1, M2 occlusion (carotid occlusions can be cervical or intracranial; with or without tandem MCA lesions) by MRA (or CTA, if MRA is technically inadequate and a CTA was performed within 60 minutes prior to the MRI) AND diffusion-weighted imaging (DWI) lesion volume \<=25 mL for an M1 or ICA occlusion and =\<15 mL for an M2 occlusion
• If CTP is technically inadequate: patient can be screened with MRI and randomized if neuroimaging criteria are met.
• Ability to comply with the study protocol, in the investigator's judgment

You may not qualify if:

• General
• Current participation in another investigational drug or device study
• Active internal bleeding
• Known hypersensitivity or allergy to any ingredients of tenecteplase
• Known bleeding diathesis
• Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency; recent oral anticoagulant therapy with INR \>1.7
• Use of one of the new oral anticoagulants within the last 48 hours (dabigatran, rivaroxaban, apixaban, edoxaban)
• Pregnant
• Intracranial neoplasm (except small meningioma), arteriovenous malformation, or aneurysm
• Seizures at stroke onset if it precludes obtaining an accurate baseline NIHSS
• Severe, uncontrolled hypertension (systolic blood pressure \>180 mmHg or diastolic blood pressure \> 110 mmHg)
• For participants with suspected coagulopathy, platelet count must be checked prior to randomization and participant is excluded if baseline platelet count \<100,000/microL
• Baseline blood glucose \>400 mg/dL (22.20 mmol/L)
• Baseline blood glucose \<50 mg/dL needs to be normalized prior to randomization
• Clot retrieval attempted using a neurothrombectomy device prior to randomization

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (97)

University of Alabama at Birmingham

Birmingham, Alabama, 35294-3300, United States

Location

Banner Desert Medical Center

Mesa, Arizona, 85202, United States

Location

Kaiser Permanente - Anaheim (E. La Palma)

Anaheim, California, 92806, United States

Location

Mills-Peninsula Medical Center

Burlingame, California, 94010, United States

Location

John Muir Health, Concord Medical Center

Concord, California, 94520, United States

Location

Sutter Davis Hospital

Davis, California, 95616, United States

Location

Kaiser Permanente - Fontana

Fontana, California, 92335, United States

Location

Adventist Health Glendale

Glendale, California, 91206, United States

Location

Kaiser Permanente South Bay Medical Center

Harbor City, California, 90710, United States

Location

UCSD Medical Center - La Jolla

La Jolla, California, 92037, United States

Location

Kaiser Permanente Los Angeles

Los Angeles, California, 90027, United States

Location

University of Southern California Medical Center

Los Angeles, California, 90033, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Cedars-Sinai Marina Del Rey Hospital

Marina del Rey, California, 90292, United States

Location

Kaiser Permanente - Ontario

Ontario, California, 91761, United States

Location

Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

Sutter Roseville Medical Center

Roseville, California, 95661, United States

Location

Sutter Medical Group, Neurology

Sacramento, California, 95816, United States

Location

UCSD - Hillcrest; Hillcrest Medical Center

San Diego, California, 92103, United States

Location

CPMC - Van Ness Campus

San Francisco, California, 94109, United States

Location

CPMC - Davies Campus

San Francisco, California, 94114, United States

Location

Torrance Memorial Medical Center

Torrance, California, 90505, United States

Location

John Muir Medical Center-Walnut Creek

Walnut Creek, California, 94598, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

University of Florida Health at Shands

Gainesville, Florida, 32608, United States

Location

Baptist Medical Center - Jacksonville

Jacksonville, Florida, 32207-8202, United States

Location

Baptist Medical Center-South

Jacksonville, Florida, 32258, United States

Location

Jackson Memorial Hospital

Miami, Florida, 33136, United States

Location

The Queen's Medical Center

Honolulu, Hawaii, 96813, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Advocate Christ Medical Center

Oak Lawn, Illinois, 60453, United States

Location

Advocate Lutheran General Hospital

Park Ridge, Illinois, 60068, United States

Location

St. Catherine Hospital

East Chicago, Indiana, 46312, United States

Location

St. Mary Medical Center

Hobart, Indiana, 46432, United States

Location

Community Hospital

Munster, Indiana, 46321, United States

Location

Uni of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Baptist Health Corbin

Corbin, Kentucky, 40701, United States

Location

Baptist Health Lexington

Lexington, Kentucky, 40503, United States

Location

Sinai Hospital of Baltimore

Baltimore, Maryland, 21215, United States

Location

Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Univ of Michigan Medical Ctr

Ann Arbor, Michigan, 48109-0718, United States

Location

Henry Ford Macomb Hospital - Clinton Township

Clinton Township, Michigan, 48038, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

McLaren Flint

Flint, Michigan, 48532, United States

Location

Spectrum Health Hospitals

Grand Rapids, Michigan, 49503, United States

Location

ProMedica Monroe Regional Hospital

Monroe, Michigan, 48162, United States

Location

Fairview Ridges Hospital

Burnsville, Minnesota, 55337, United States

Location

Fairview Southdale

Edina, Minnesota, 55435, United States

Location

U of Minnesota MedCtr Fairview

Minneapolis, Minnesota, 55455, United States

Location

Sanford Worthington Medical Center

Worthington, Minnesota, 56187, United States

Location

Washington University

St Louis, Missouri, 63128, United States

Location

JFK Neuroscience Institute

Edison, New Jersey, 08820, United States

Location

Atlantic Health System - Overlook Medical Center

Summit, New Jersey, 07901, United States

Location

Capital Health Regional Medical Center

Trenton, New Jersey, 08638, United States

Location

Buffalo General Medical Center

Buffalo, New York, 14203, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Mission Hospitals Inc

Asheville, North Carolina, 28803, United States

Location

Guilford Neurologic Research

Greensboro, North Carolina, 27405, United States

Location

Univ of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Riverside Methodist Hospital; Cancer Services

Columbus, Ohio, 43214-1419, United States

Location

Grant Medical Center

Columbus, Ohio, 43215, United States

Location

Doctors Hospital

Columbus, Ohio, 43228, United States

Location

ProMedica Toledo Hospital

Toledo, Ohio, 43606, United States

Location

Ascension St. John

Tulsa, Oklahoma, 74104, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Adventist Health Portland

Portland, Oregon, 97216, United States

Location

Providence Saint Vincent's Medical Center

Portland, Oregon, 97225, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

UPMC East Hospital

Monroeville, Pennsylvania, 15146, United States

Location

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Uni of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Pennsylvania Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

UPMC Mercy

Pittsburgh, Pennsylvania, 15219, United States

Location

UPMC Passavant Hospital

Pittsburgh, Pennsylvania, 15237, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Sanford Neurology Clinic

Sioux Falls, South Dakota, 57104, United States

Location

Chattanooga Center for Neurologic Research

Chattanooga, Tennessee, 37404, United States

Location

Saint Thomas Rutherford Hospital

Murfreesboro, Tennessee, 37129, United States

Location

Saint Thomas Health

Nashville, Tennessee, 37205, United States

Location

Saint Thomas Midtown Hospital

Nashville, Tennessee, 37232, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Dell Seton Medical center at the University of Texas

Austin, Texas, 78701, United States

Location

Seton Medical Center Austin

Austin, Texas, 78705, United States

Location

Valley Baptist Medical Center-Brownsville

Brownsville, Texas, 78520, United States

Location

Baylor University Medical Center

Dallas, Texas, 75231, United States

Location

Valley Baptist Medical Center

Harlingen, Texas, 78550, United States

Location

University of Texas at Houston; Neurology

Houston, Texas, 77030, United States

Location

Ascension Seton Hays

Kyle, Texas, 78640, United States

Location

Ascension Seton Williamson

Round Rock, Texas, 78665, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

University of Virginia

Charlottesville, Virginia, 22906, United States

Location

Uni of Alberta

Edmonton, Alberta, T6G 2G3, Canada

Location

Hamilton General Hospital; Pharmacy

Hamilton, Ontario, L8L 2X2, Canada

Location

Montreal Neurological Inst; Clinical Research Unit

Montreal, Quebec, H3A 2B4, Canada

Location

Related Publications (3)

• Albers GW, Jumaa M, Purdon B, Zaidi SF, Streib C, Shuaib A, Sangha N, Kim M, Froehler MT, Schwartz NE, Clark WM, Kircher CE, Yang M, Massaro L, Lu XY, Rippon GA, Broderick JP, Butcher K, Lansberg MG, Liebeskind DS, Nouh A, Schwamm LH, Campbell BCV; TIMELESS Investigators. Tenecteplase for Stroke at 4.5 to 24 Hours with Perfusion-Imaging Selection. N Engl J Med. 2024 Feb 22;390(8):701-711. doi: 10.1056/NEJMoa2310392. Epub 2024 Feb 8.

  PMID: 38329148 DERIVED

• Zachrison KS, Amati V, Schwamm LH, Yan Z, Nielsen V, Christie A, Reeves MJ, Sauser JP, Lomi A, Onnela JP. Influence of Hospital Characteristics on Hospital Transfer Destinations for Patients With Stroke. Circ Cardiovasc Qual Outcomes. 2022 May;15(5):e008269. doi: 10.1161/CIRCOUTCOMES.121.008269. Epub 2022 Apr 4.

  PMID: 35369714 DERIVED

• Albers GW, Campbell BC, Lansberg MG, Broderick J, Butcher K, Froehler MT, Schwamm LH, Nouh AM, Liebeskind DS, Toy F, Yang M, Massaro L, Schoeffler M, Purdon B. A Phase III, prospective, double-blind, randomized, placebo-controlled trial of thrombolysis in imaging-eligible, late-window patients to assess the efficacy and safety of tenecteplase (TIMELESS): Rationale and design. Int J Stroke. 2023 Feb;18(2):237-241. doi: 10.1177/17474930221088400. Epub 2022 Apr 1.

  PMID: 35262424 DERIVED

MeSH Terms

Interventions

Tenecteplase

Intervention Hierarchy (Ancestors)

Tissue Plasminogen Activator; Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

1-800-821-8590

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: December 19, 2018
• First Posted: December 24, 2018
• Study Start: March 2, 2019
• Primary Completion: February 28, 2023
• Study Completion: February 28, 2023
• Last Updated: May 22, 2024
• Results First Posted: May 22, 2024

Record last verified: 2024-05

Locations

US (94); CA (3)