Clinical trial NCT05484154: Efficacy and Safety Evaluation of 3K3A-APC in Ischemic Stroke
Official title: A Phase 3 Study to Evaluate the Efficacy and Safety of 3K3A-APC in Combination with Tissue Plasminogen Activator, Mechanical Thrombectomy, or Both in Subjects with Moderate to Severe Acute Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Ischemic Stroke
Keywords: Ischemic Stroke
Stroke
APC
3K3A
3K3A-APC
Activated protein C
RHAPSODY
Lead sponsor: ZZ Biotech, LLC
Sponsor class: INDUSTRY
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
name: University of Southern California
name: University of Cincinnati
name: University of South Carolina
First posted: 2022-08-02
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: To evaluate the effect of 3K3A-APC on 90-day disability
timeFrame: Day 90 mRS
Secondary outcomes:
measure: To evaluate the safety of 3K3A-APC
timeFrame: Baseline to Day 90
Other outcomes:
Locations:
Study officials:
affiliation: University of Southern California
name: Patrick D Lyden, MD
role: PRINCIPAL_INVESTIGATOR
References: