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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
ZZ Biotech, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

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

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept 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

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

    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
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    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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