Ischemic Stroke
Conditions
Keywords
Ischemic Stroke, Stroke, APC, 3K3A, 3K3A-APC, Activated protein C, RHAPSODY
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.
Interventions
BIOLOGICAL3K3A-APC
3K3A-APC, diluted in 0.9% sodium chloride in water, given at 100 mL IV infusion
OTHERPlacebo
Matching placebo, 0.9% sodium chloride in water, given at 100 mL IV infusion
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
University of Southern California
University of Cincinnati
University of South Carolina
ZZ Biotech, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Outcome results
None listed