Phase 2
Completed N=110
Safety Evaluation of 3K3A-APC in Ischemic Stroke
Source: ClinicalTrials.gov NCT02222714 ↗Enrolled (actual)
110
Serious AEs
44.3%
Results posted
Nov 2018
Primary outcomePrimary: Number of Participants With Adverse Events That Meet Dose-limiting Toxicity (DLT) Criteria Specified in Protocol — 0; 1; 0; 0 Participants
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events That Meet Dose-limiting Toxicity (DLT) Criteria Specified in Protocol |
0; 1; 0; 0; 1; 0 | — |
| SECONDARY Number of Participants With a Presence of Measurable Bleeds in the Brain (Hemorrhage and Microbleeds) as Determined by 1.5T MRI |
24; 25; 7; 8 | — |
| SECONDARY PK of 3K3A-APC by Compartmental Analysis (Clearance) |
20994; 17814; 18504; 24403 | — |
| SECONDARY PK of 3K3A-APC by Compartmental Analysis (Volume of Distribution) |
8242; 6051; 7164; 11437 | — |
| SECONDARY PK of 3K3A-APC by Compartmental Analysis (Cmax) |
0.957; 2.37; 2.80; 3.32 | — |
| SECONDARY PK of 3K3A-APC by Compartmental Analysis (AUC[0-inf]) |
0.513; 1.16; 1.49; 2.06 | — |
| SECONDARY PK of 3K3A-APC by Compartmental Analysis (λz) |
2.55; 2.94; 2.58; 2.13 | — |
| SECONDARY PK of 3K3A-APC by Compartmental Analysis (Half-life) |
0.272; 0.235; 0.268; 0.325 | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT02222714). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.