Tenecteplase for Stroke

(DoubleDoseTNK Trial)

Overseen By Alexandra L Czap, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Hermann Health System

Must not be taking: Antiplatelets, Amyloid therapy, Anticoagulants

Disqualifiers: LVO, MeVO, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a second dose of the clot-busting drug Tenecteplase can safely aid stroke patients who did not respond well to the initial dose. It targets individuals who received their first Tenecteplase dose within 3 hours of last being known to be well and showed no improvement or worsened within 45 minutes after that dose. Candidates with ongoing stroke symptoms after the first dose, confirmed by a CT scan to show no brain bleeding, may be suitable participants. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating. Specifically, you cannot be on more than one antiplatelet agent within 48 hours prior to enrollment, and you must not have used certain blood thinners like warfarin or direct oral anticoagulants within specified time frames before joining the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that Tenecteplase is generally safe for treating sudden strokes caused by blocked blood flow. In past studies, researchers compared Tenecteplase to a similar treatment called Alteplase. Both treatments had similar safety outcomes, with rare concerns about bleeding in the brain and death. Most patients tolerated Tenecteplase well.

Another study found that patients treated with Tenecteplase often recovered well. Although there is always a risk of bleeding, research suggests this treatment does not significantly increase that risk compared to other options.

This trial is in its early phase, focusing mainly on safety. Early-phase trials usually involve close monitoring to ensure the treatment is safe. While Tenecteplase has shown a good safety record in other studies, this trial will help confirm its safety when using a second dose in certain situations. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for stroke, which typically include drugs like alteplase, tenecteplase offers a unique approach by potentially allowing for a second dose if initial improvements are insufficient or if patients worsen. This feature could make tenecteplase a more adaptable option for managing acute scenarios within a critical time window. Researchers are excited because tenecteplase may provide a more flexible and responsive treatment option, potentially improving outcomes for patients who don't respond adequately to the initial dose.

What evidence suggests that Tenecteplase might be an effective treatment for stroke?

Research has shown that Tenecteplase (TNK) can help people recover from a stroke more quickly by clearing blocked blood vessels, leading to faster regaining of abilities. In some studies, about 37% of people treated with Tenecteplase experienced excellent recovery within 90 to 120 days after their stroke, similar to results from another common treatment, alteplase. In this trial, participants will receive a double dose of Tenecteplase if they meet specific criteria, such as not showing clinical improvement within 45 minutes of the first dose. Overall, Tenecteplase has shown promise in aiding stroke recovery. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for acute ischemic stroke patients who haven't improved after a first dose of Tenecteplase within 3 hours from symptom onset, have an NIHSS score over 6, and can receive a second dose within 4.5 hours. They must not show bleeding on a CT scan and meet standard criteria for Tenecteplase.

Inclusion Criteria

NIHSS > 6 for both first and second dose

Time from LKN < 3 hrs (first dose) and < 4.5 hours (second dose)

Patient/legally authorized representative has signed the Informed Consent Form

Exclusion Criteria

I am scheduled for a clot removal procedure before my second dose of TENECTEPLASE.

I've used heparin recently and my blood test shows slower clotting.

I have a bleeding disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Initial Treatment

Participants receive the first dose of IV Tenecteplase within 3 hours of last known normal

Immediate

1 visit (in-person)

Second Dose Administration

Participants receive a second dose of IV Tenecteplase if they do not improve within 45 minutes of the first dose or deteriorate after initial improvement

Within 4.5 hours of last known normal

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including neuro checks and NIHSS assessments

90 days

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Tenecteplase

Trial Overview The study tests the safety of giving a second dose of Tenecteplase to stroke patients who don't respond to the initial treatment. It measures severe bleeding risks and changes in neurological status immediately after treatment and at follow-up.

How Is the Trial Designed?

Group I: Patients receiving double dose TNK Experimental Treatment 1 Intervention

The investigators will give a second dose of IV TNK to patients receiving the initial TNK dose within 3 hrs of LKN, have a baseline NIHSS \> 6, and who do not clinically improve within 45 minutes of the first dose, or who improve but then deteriorate, and can still be treated within 4.5 hours from LKN. Patients will require a second CT scan to rule out any bleeding, and meet the usual inclusion and exclusion criteria for TNK treatment, before the second dose which must be given within 4.5 hrs of LKN. Both TNK doses will be 0.25 mg/kg. The initial TNK dose may be given on the MSU or ED, and the second dose in the ED.

Who Is Running the Clinical Trial?

Memorial Hermann Health System

Lead Sponsor

Trials

10

Recruited

2,002,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Grotta Stroke Research Foundation

Collaborator

Trials

1

Recruited

20+

Memorial Hermann Hospital Mobile Stroke Unit

Collaborator

Trials

1

Recruited

20+

The University of Texas Health Science Center, Houston

Collaborator

Trials

974

Recruited

361,000+

Published Research Related to This Trial

In a study involving 1585 patients across 5 randomized clinical trials, tenecteplase showed significantly greater complete recanalization and early neurological improvement compared to alteplase in treating acute ischemic stroke.

Both treatments had similar safety profiles, with no significant differences in rates of recovery, functional independence, or serious complications like intracerebral hemorrhage, indicating that tenecteplase is at least as effective and safe as alteplase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenecteplase versus alteplase for management of acute ischemic stroke: a pairwise and network meta-analysis of randomized clinical trials. Kheiri, B., Osman, M., Abdalla, A., et al.[2018]

A comprehensive analysis of 19,514,140 case reports revealed that while tenecteplase is as effective as alteplase for treating acute ischemic stroke, it has a higher incidence of serious adverse events (AEs) such as death and cardiogenic shock, indicating potential safety concerns.

Unexpected adverse reactions, including ocular issues and pneumonia aspiration, were identified with tenecteplase, highlighting the need for ongoing monitoring to ensure patient safety before it can be considered a full alternative to alteplase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing adverse events of tenecteplase and alteplase: a real-world analysis of the FDA adverse event reporting system (FAERS). Shi, FE., Yu, Z., Sun, C., et al.[2023]

In a meta-analysis of four randomized controlled trials with 1334 patients, tenecteplase showed a significant improvement in early major neurological outcomes compared to alteplase for treating acute ischemic stroke.

However, there were no significant differences in long-term functional outcomes, rates of intracerebral hemorrhage, or mortality between the two treatments, suggesting that while tenecteplase may offer early benefits, its overall safety and efficacy are comparable to alteplase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenecteplase versus alteplase in acute ischemic stroke: systematic review and meta-analysis. Thelengana, A., Radhakrishnan, DM., Prasad, M., et al.[2020]

In a study of 165 patients treated with tenecteplase for ischemic stroke, the safety profile was comparable to that of 254 patients treated with alteplase, with similar rates of symptomatic intracranial hemorrhage (1.8% vs. 2.7%) and angioedema (2.4% vs. 0.4%).

The use of tenecteplase was found to be feasible and effective, showing no significant difference in functional independence at 90 days compared to alteplase, indicating it can be a viable alternative for stroke treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Routine Use of Tenecteplase for Thrombolysis in Acute Ischemic Stroke. Zhong, CS., Beharry, J., Salazar, D., et al.[2021]

Tenecteplase is as safe and effective as alteplase for treating acute ischemic stroke, based on a meta-analysis of 14 studies involving 3537 patients, showing no significant differences in 90-day outcomes.

Patients treated with tenecteplase may experience higher rates of early neurological improvement compared to those treated with alteplase, suggesting a potential advantage in the initial recovery phase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenecteplase vs. alteplase for the treatment of patients with acute ischemic stroke: a systematic review and meta-analysis. Ma, P., Zhang, Y., Chang, L., et al.[2022]

Citations

1. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.125.053256

Tenecteplase for Acute Ischemic Stroke at 4.5 to 24 Hours The primary outcome was excellent functional outcome (modified Rankin Scale score, 0–1) at 90 days, with additional efficacy and safety end ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12402402/

Efficacy and Safety of Tenecteplase in Acute Ischemic Stroke Tenecteplase improves early neurological recovery and recanalization and provides excellent functional outcomes in acute ischemic stroke.

3. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2402980

Tenecteplase for Ischemic Stroke at 4.5 to 24 Hours without ... Mortality at 90 days was 13.3% with tenecteplase and 13.1% with standard medical treatment, and the incidence of symptomatic intracranial ...

4. tnkase.com tnkase.com/acute-ischemic-stroke/clinical-data/act-trial-efficacy.html

TNKase® (tenecteplase) | Efficacy in Acute Ischemic Stroke 37% of TNKase-treated patients had excellent functional outcomes (defined as mRS 0-1) 90 to 120 days following a stroke vs ~36% for alteplase.

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2831320

Safety and Effectiveness for Tenecteplase and Alteplase in ... This comparative effectiveness study compares the clinical effectiveness and safety of tenecteplase and alteplase for the treatment of acute ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1052305725001168

An updated meta-analysis of randomized controlled trials In our meta-analysis, we found significantly improved excellent functional outcomes with TNK administration in the extended time window. This can be linked to ...