Efficacy and Safety Evaluation of 3K3A-APC in Ischemic Stroke (RHAPSODY-2)

ZZ Biotech

Status and phase: Withdrawn; Phase 3

Conditions: Ischemic Stroke

Treatments: Biological: 3K3A-APC; Other: Placebo

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT05484154

UG3NS119199 (U.S. NIH Grant/Contract)

ZZ-3K3A-301

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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0 participants in 4 patient groups, including a placebo group

10mg of 3K3A-APC

Active Comparator group

Description:

3K3A-APC, q12h for up to 5 doses

Treatment:

Biological: 3K3A-APC

15mg of 3K3A-APC

Active Comparator group

Description:

3K3A-APC, q12h for up to 5 doses

Treatment:

Biological: 3K3A-APC

30mg of 3K3A-APC

Active Comparator group

Description:

3K3A-APC, q12h for up to 5 doses

Treatment:

Biological: 3K3A-APC

Placebo

Placebo Comparator group

Description:

Matching placebo, q12h for up to 5 doses

Treatment:

Other: Placebo