Safety Evaluation of 3K3A-APC in Ischemic Stroke
Safety Evaluation of 3K3A-APC in Ischemic Stroke
The purpose of this study was to evaluate the safety, pharmacokinetics (PK) and preliminary
 efficacy of multiple ascending intravenous doses of 3K3A-APC, a Recombinant Variant of Human
 activated protein C (APC), in in the treatment of acute ischemic stroke following treatment
 with recombinant tissue plasminogen activator (tPA), mechanical thrombectomy or both.
This was a multicenter, prospective, randomized, controlled, double-blinded Phase 2 study
 intended to evaluate the safety, PK and preliminary efficacy of 3K3A-APC following treatment
 with tPA, mechanical thrombectomy or both in subjects with moderate to severe acute ischemic
 stroke.

 Approximately 115 subjects were to be randomized, which included the planned 88 subjects in
 groups of 4 subjects to either 3K3A-APC or placebo (in a 3:1 ratio) and the additional
 placebo subjects who were enrolled during safety review pauses. This study used a modified
 version of the continual reassessment method (CRM) in order to establish a maximum tolerated
 dose (MTD).

 Eligible subjects received 3K3A-APC or placebo every 12 hours for up to 5 doses
 (approximately 3 days), or until discharge from the hospital, whichever occurred first.
 Subjects were monitored for safety evaluations through Day 7 (or discharge, if earlier) and
 were expected to be seen on Day 7, 14, 30, and 90 for safety and outcome evaluations.
Inclusion Criteria:

 -  Acute ischemic stroke

 -  Able to receive IV tPA, mechanical thrombectomy or both

 -  National Institutes of Health Stroke Scale (NIHSS) score of ≥ 5

 -  Signed informed consent

 -  Mechanical thrombectomy subjects only: onset time to arterial puncture time < 6 hours

 Exclusion Criteria:

 -  History of stroke or penetrating head injury within 90 days prior to enrollment

 -  History of previous or current diagnosis of intracranial hemorrhage that represents a
 potential for re-hemorrhage if subjected to thrombolytic therapy or mechanical
 thrombectomy

 -  Moyamoya disease, cerebral arterio-venous malformation (AVM), known unsecured aneurysm
 requiring intervention during the acute study period

 -  Presence of other neurological or non-neurological co-morbidities that may lead,
 independently of the current stroke, to further deterioration in the subject's
 neurological status during the trial period

 -  Presence of premorbid neurological deficits and functional limitations assessed by a
 retrospective Modified Rankin Scale (mRS) score of ≥ 2

 -  Mechanical thrombectomy subjects only: baseline non-contrast CT scan revealing a large
 core occlusion as defined by local protocol

 -  Prolonged prothrombin time (PT) or activated partial thromboplastin time (aPTT)

 -  Severe hypertension or hypotension

 -  Glomerular filtration rate (GFR) <35 mL/min

 -  Blood glucose concentration < 50 mg/dL

 -  Prior exposure to any exogenous form of APC