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

Phase 3

Withdrawn

• Conditions: Ischemic Stroke
• Interventions: Other: Placebo; Biological: 3K3A-APC

• Registration Number: NCT05484154
• Lead Sponsor: ZZ Biotech, LLC

Brief Summary

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

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 Timeline

• Study First Submitted: 2022-07-29
• Study First Submitted QC: 2022-07-29
• Study First Posted: 2022-08-02
• Status Verified: 2024-09
• Last Update Submitted: 2024-09-26
• Last Update Posted: 2024-09-30
• Study Start: 2024-10
• Primary Completion: 2026-07
• Study Completion: 2026-10

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: 1400

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Matching placebo, q12h for up to 5 doses
15mg of 3K3A-APC	3K3A-APC	3K3A-APC, q12h for up to 5 doses
30mg of 3K3A-APC	3K3A-APC	3K3A-APC, q12h for up to 5 doses
10mg of 3K3A-APC	3K3A-APC	3K3A-APC, q12h for up to 5 doses

Primary Outcome Measures

Name	Time	Method
To evaluate the effect of 3K3A-APC on 90-day disability	Day 90 mRS	Day 90 mRS scores will be compared between groups using ordinal (shift) analysis

Secondary Outcome Measures

Name	Time	Method
To evaluate the safety of 3K3A-APC	Baseline to Day 90	The percentage of subjects who experienced any treatment-related AE will be compared using a Fisher's exact test.