Efficacy and Safety Evaluation of 3K3A-APC in Ischemic Stroke (RHAPSODY-2)
Primary Purpose
Ischemic Stroke
Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
3K3A-APC
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Ischemic Stroke focused on measuring Ischemic Stroke, Stroke, APC, 3K3A, 3K3A-APC, Activated protein C, RHAPSODY
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
10mg of 3K3A-APC
15mg of 3K3A-APC
30mg of 3K3A-APC
Placebo
Arm Description
3K3A-APC, q12h for up to 5 doses
3K3A-APC, q12h for up to 5 doses
3K3A-APC, q12h for up to 5 doses
Matching placebo, q12h for up to 5 doses
Outcomes
Primary Outcome Measures
To evaluate the effect of 3K3A-APC on 90-day disability
Day 90 mRS scores will be compared between groups using ordinal (shift) analysis
Secondary Outcome Measures
To evaluate the safety of 3K3A-APC
The percentage of subjects who experienced any treatment-related AE will be compared using a Fisher's exact test.
Full Information
NCT ID
NCT05484154
First Posted
July 29, 2022
Last Updated
July 11, 2023
Sponsor
ZZ Biotech, LLC
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), University of Southern California, University of Cincinnati, University of South Carolina
1. Study Identification
Unique Protocol Identification Number
NCT05484154
Brief Title
Efficacy and Safety Evaluation of 3K3A-APC in Ischemic Stroke
Acronym
RHAPSODY-2
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
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 2023 (Anticipated)
Primary Completion Date
July 2026 (Anticipated)
Study Completion Date
October 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ZZ Biotech, LLC
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), University of Southern California, University of Cincinnati, University of South Carolina
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Stroke
Keywords
Ischemic Stroke, Stroke, APC, 3K3A, 3K3A-APC, Activated protein C, RHAPSODY
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1400 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
10mg of 3K3A-APC
Arm Type
Active Comparator
Arm Description
3K3A-APC, q12h for up to 5 doses
Arm Title
15mg of 3K3A-APC
Arm Type
Active Comparator
Arm Description
3K3A-APC, q12h for up to 5 doses
Arm Title
30mg of 3K3A-APC
Arm Type
Active Comparator
Arm Description
3K3A-APC, q12h for up to 5 doses
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo, q12h for up to 5 doses
Intervention Type
Biological
Intervention Name(s)
3K3A-APC
Other Intervention Name(s)
3K3A-Activated Protein C
Intervention Description
3K3A-APC, diluted in 0.9% sodium chloride in water, given at 100 mL IV infusion
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
Matching Placebo
Intervention Description
Matching placebo, 0.9% sodium chloride in water, given at 100 mL IV infusion
Primary Outcome Measure Information:
Title
To evaluate the effect of 3K3A-APC on 90-day disability
Description
Day 90 mRS scores will be compared between groups using ordinal (shift) analysis
Time Frame
Day 90 mRS
Secondary Outcome Measure Information:
Title
To evaluate the safety of 3K3A-APC
Description
The percentage of subjects who experienced any treatment-related AE will be compared using a Fisher's exact test.
Time Frame
Baseline to Day 90
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kent Pryor, PhD, MBA
Phone
+1 (619) 574 0820
Email
kpryor@zzbiotech.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick D Lyden, MD
Organizational Affiliation
University of Southern California
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
https://zzbiotech.com/stroke-program/scientific-papers
Description
ZZ Biotech Scientific References
Learn more about this trial
Efficacy and Safety Evaluation of 3K3A-APC in Ischemic Stroke
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