Improving Early Reperfusion With Adjuvant Dornase Alfa in Large Vessel Ischemic Stroke (EXTEND-IA DNase)

NCT05203224 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: MBC2101
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 3

Brief Summary

Patients presenting to the emergency department with acute ischemic stroke, who are are eligible for standard intravenous thrombolytic therapy within 4.5 hours of stroke onset will be assessed for major vessel occlusion to determine their eligibility for the trial. All participants will receive intravenous tenecteplase (or alteplase due to manufacturer shortage) and endovascular thrombectomy as standard care. The trial is a Bayesian Optimised Phase 2 dose-finding umbrella trial (single arm versus objective performance criterion of 20% substantial reperfusion prior to endovascular thrombectomy based on the EXTEND-IA TNK trials NCT02388061, NCT03340493). The aim is to determine the optimal dose of intravenous dornase alfa (recombinant human DNase 1) with sufficient promise to take forward in a seamless phase 2b/3 design.

Conditions

Ischemic Stroke

Keywords

thrombolysis; thrombolytic; endovascular thrombectomy; tenecteplase; dornase alfa; DNase

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with substantial angiographic reperfusion or absence of retrievable intracranial thrombus at initial angiogram without symptomatic intracerebral hemorrhage

  composite outcome of reperfusion on initial angiogram (day 0 - expanded Treatment In Cerebral Infarction \[eTICI\] 2b-3 or no retrievable intracranial thrombus) and assessment of symptomatic intracerebral hemorrhage on brain imaging 24h post-treatment. eTICI 2b-3 indicates reperfusion of \>50% of the initially involved arterial territory.

  24 hours post-treatment

Other Outcomes (7)

• modified Rankin Scale (mRS) at 3 months

  3 months post stroke

• modified Rankin Scale (mRS) 0-1 or no change from baseline at 3 months

  3 months post stroke

• modified Rankin Scale (mRS) 0-2 or no change from baseline at 3 months

  3 months post stroke

Study Arms (1)

Intravenous Dornase alfa (DNase)

EXPERIMENTAL

Patients will receive a single intravenous dose of dornase alfa (at either 0.125mg/kg, 0.25mg/kg, 0.5mg/kg or 1mg/kg in escalating tiers), administered as a bolus over \~30 seconds.

Drug: Dornase Alfa

Interventions

Dornase Alfa DRUG

Intravenous Dornase alfa

Also known as: DNase, Pulmozyme

Intravenous Dornase alfa (DNase)

Eligibility Criteria

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

You may qualify if:

• Patients presenting with acute ischemic stroke eligible, using standard criteria, to receive IV thrombolytics within 4.5 hours of stroke onset
• Patient's age is ≥18 years
• Arterial occlusion on CTA or MRA of the ICA, M1, M2 or basilar artery

You may not qualify if:

• Intracranial hemorrhage (ICH) identified by CT or MRI
• Rapidly improving symptoms at the discretion of the investigator
• Pre-stroke mRS score of ≥ 4 (indicating previous disability)
• Hypodensity in \>1/3 MCA territory or equivalent proportion of basilar artery territory on non-contrast CT
• Contraindication to imaging with contrast agents
• Any terminal illness such that patient would not be expected to survive more than 1 year
• Any condition that, in the judgment of the investigator could impose hazards to the patient if study therapy is initiated or affect the participation of the patient in the study.
• Pregnant or lactating women

Sponsors & Collaborators

• University of Melbourne: lead

Study Sites (3)

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

Related Publications (1)

• Di G, Vazquez-Reyes S, Diaz B, Pena-Martinez C, Garcia-Culebras A, Cuartero MI, Moraga A, Pradillo JM, Esposito E, Lo EH, Moro MA, Lizasoain I. Daytime DNase-I Administration Protects Mice From Ischemic Stroke Without Inducing Bleeding or tPA-Induced Hemorrhagic Transformation, Even With Aspirin Pretreatment. Stroke. 2025 Feb;56(2):527-532. doi: 10.1161/STROKEAHA.124.049961. Epub 2025 Jan 27.

  PMID: 39869712 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Interventions

dornase alfa; Deoxyribonucleases

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Esterases; Hydrolases; Enzymes; Enzymes and Coenzymes

Study Officials

• Bruce CV Campbell, MBBS PhD

  University of Melbourne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: No blinding given single arm study but Independent core laboratory adjudication of the primary outcome, mRS (secondary outcome) performed by central assessor.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Bayesian Optimised Phase 2 dose-finding umbrella trial

Study Record Dates

• First Submitted: January 10, 2022
• First Posted: January 24, 2022
• Study Start: February 18, 2022
• Primary Completion: November 24, 2025
• Study Completion: February 25, 2026
• Last Updated: May 6, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Time Frame: 2 years after the publication of the primary manuscript
• Access Criteria: Qualified investigators can access data after submission of a project proposal that has been approved by the VISTA steering committee.

Locations

AU (3)