Efficacy and Safety Evaluation of 3K3A-APC in Ischemic Stroke

NCT ID: NCT05484154

Last Updated: 2024-10-01

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

WITHDRAWN

Clinical Phase

PHASE3

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-31

Study Completion Date

2026-10-31

Brief Summary

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The purpose of this study is to evaluate the efficacy and safety of intravenous doses of 3K3A-APC, a recombinant variant of human activated protein C (APC), in the treatment of acute ischemic stroke following treatment with thrombolysis, mechanical thrombectomy or both.

Detailed Description

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This multicenter, randomized, placebo-controlled, double-blind, Phase 3 study is being performed in coordination with StrokeNet to evaluate efficacy and safety of 3K3A-APC following administration of thrombolysis, mechanical thrombectomy, or both in subjects with moderate to severe acute ischemic stroke.

The study will be conducted in two phases. During a lead-in dose-finding phase, a maximum of 360 subjects will be randomized to 3K3A-APC or placebo using a Bayesian adaptive approach. Randomized subjects will receive 3K3A-APC or placebo every 12 hours for up to 5 doses (approximately 3 days) or until discharge from the hospital (whichever occurs first). The lead-in phase will transition to one selected 3K3A APC dose-and recruitment will continue-when a single dose proves superior to all other doses and safe.

The definitive phase will continue with the selected dose of 3K3A-APC from the lead-in phase. Randomization will be stratified on 4 variables. Lead-in patients who received the dose selected for the definitive phase will be included in the final data analysis.

Conditions

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Ischemic Stroke

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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10mg of 3K3A-APC

3K3A-APC, q12h for up to 5 doses

Group Type ACTIVE_COMPARATOR

3K3A-APC

Intervention Type BIOLOGICAL

3K3A-APC, diluted in 0.9% sodium chloride in water, given at 100 mL IV infusion

15mg of 3K3A-APC

3K3A-APC, q12h for up to 5 doses

Group Type ACTIVE_COMPARATOR

3K3A-APC

Intervention Type BIOLOGICAL

3K3A-APC, diluted in 0.9% sodium chloride in water, given at 100 mL IV infusion

30mg of 3K3A-APC

3K3A-APC, q12h for up to 5 doses

Group Type ACTIVE_COMPARATOR

3K3A-APC

Intervention Type BIOLOGICAL

3K3A-APC, diluted in 0.9% sodium chloride in water, given at 100 mL IV infusion

Placebo

Matching placebo, q12h for up to 5 doses

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Matching placebo, 0.9% sodium chloride in water, given at 100 mL IV infusion

Interventions

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3K3A-APC

3K3A-APC, diluted in 0.9% sodium chloride in water, given at 100 mL IV infusion

Intervention Type BIOLOGICAL

Placebo

Matching placebo, 0.9% sodium chloride in water, given at 100 mL IV infusion

Intervention Type OTHER

Other Intervention Names

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3K3A-Activated Protein C Matching Placebo

Eligibility Criteria

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Inclusion Criteria

* Acute ischemic stroke
* Able to receive thrombolysis, mechanical thrombectomy or both
* National Institutes of Health Stroke Scale (NIHSS) score of ≥ 5
* Signed informed consent
* Agreement to use effective birth control throughout the study

Exclusion Criteria

* Neurologic deficit is non-disabling
* History of stroke or penetrating head injury within 90 days prior to enrollment
* History of previous or current diagnosis of intracranial hemorrhage
* Moyamoya disease, cerebral arteriovenous malformation, or known unsecured aneurysm requiring intervention during the acute study period
* Presence of tandem lesions suggesting a likely need for proximal artery stenting during the thrombectomy procedure that would mandate post-operative dual antiplatelet therapy
* Presence of other neurological or non-neurological co-morbidities, independently of the current stroke, that may lead to further deterioration in the subject's neurological status during the study period
* Prolonged prothrombin time (PT) or activated partial thromboplastin time (aPTT)
* Severe hypertension or hypotension
* Blood glucose concentration \< 50 mg/dL
* Prior exposure to any exogenous form of a recombinant variant of human APC
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

University of Southern California

OTHER

Sponsor Role collaborator

University of Cincinnati

OTHER

Sponsor Role collaborator

University of South Carolina

OTHER

Sponsor Role collaborator

ZZ Biotech, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Patrick D Lyden, MD

Role: PRINCIPAL_INVESTIGATOR

University of Southern California

Other Identifiers

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UG3NS119199

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ZZ-3K3A-301

Identifier Type: -

Identifier Source: org_study_id

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