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

ZZ Biotech, LLC

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Conditions

Ischemic Stroke

Interventions

3K3A-APCBIOLOGICAL

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

PlaceboOTHER

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

To evaluate the effect of 3K3A-APC on 90-day disability

Day 90 mRS scores will be compared between groups using ordinal (shift) analysis

Time frame: Day 90 mRS

Secondary Outcomes

To evaluate the safety of 3K3A-APC

The percentage of subjects who experienced any treatment-related AE will be compared using a Fisher's exact test.

Time frame: Baseline to Day 90

Data from ClinicalTrials.gov

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