Ischemic StrokePhase 3RHAPSODY-2NCT05484154
Efficacy and Safety Evaluation of 3K3A-APC in Ischemic Stroke
A Phase 3 study testing 3K3A-APC in people with Ischemic Stroke, run by ZZ Biotech, LLC.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Ischemic Stroke
- What is being tested?
- 3K3A-APC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Oct 2024to Oct 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
About this study
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
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.
Read the 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.
- Conditions
- Ischemic Stroke
- Being tested
- 3K3A-APC, Placebo
- Keywords
- Ischemic Stroke, Stroke, APC, 3K3A, 3K3A-APC, Activated protein C, RHAPSODY
- Medical subject headings
- Ischemic Stroke, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3K3A-APCBiological
Also called 3K3A-Activated Protein C
3K3A-APC, diluted in 0.9% sodium chloride in water, given at 100 mL IV infusion
PlaceboOther
Also called Matching Placebo
Matching placebo, 0.9% sodium chloride in water, given at 100 mL IV infusion
| Study group | Role | What they receive |
|---|---|---|
| 10mg of 3K3A-APC | Active comparator | 3K3A-APC, q12h for up to 5 doses Receives: Biological: 3K3A-APC |
| 15mg of 3K3A-APC | Active comparator | 3K3A-APC, q12h for up to 5 doses Receives: Biological: 3K3A-APC |
| 30mg of 3K3A-APC | Active comparator | 3K3A-APC, q12h for up to 5 doses Receives: Biological: 3K3A-APC |
| Placebo | Placebo comparator | Matching placebo, q12h for up to 5 doses Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the effect of 3K3A-APC on 90-day disability
Day 90 mRS scores will be compared between groups using ordinal (shift) analysis
Measured: Day 90 mRS
Secondary outcomes (1)
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.
Measured: Baseline to Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2022
- Study startOct 2024 (estimated)
- Primary completionJul 2026 (estimated)
- Study completionOct 2026 (estimated)
Why it stopped: NIH funding suspension.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- ZZ Biotech, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), University of Southern California, University of Cincinnati, University of South Carolina
- Responsible party
- Sponsor
- Investigators
- Patrick D Lyden, MD, Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05484154
- Sponsor's protocol ID
- ZZ-3K3A-301
- Other IDs
- UG3NS119199
- Acronym
- RHAPSODY-2
- Status last verified
- Sep 2024
- First submitted
- 29 Jul 2022
- Last updated
- 1 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05484154
- Acronym / sponsor ID
- RHAPSODY-2 / ZZ-3K3A-301
- Conditions
- Ischemic Stroke
- Keywords
- Ischemic Stroke, Stroke, APC, 3K3A, 3K3A-APC, Activated protein C, RHAPSODY
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: NIH funding suspension.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- ZZ Biotech, LLCIndustry (pharma, biotech, devices)
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), University of Southern California, University of Cincinnati, University of South Carolina
- Study start
- Oct 2024 (estimated)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Oct 2026 (estimated)
- First posted
- 2 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 10mg of 3K3A-APC | Active comparator | Biological: 3K3A-APC3K3A-APC, q12h for up to 5 doses |
| 15mg of 3K3A-APC | Active comparator | Biological: 3K3A-APC3K3A-APC, q12h for up to 5 doses |
| 30mg of 3K3A-APC | Active comparator | Biological: 3K3A-APC3K3A-APC, q12h for up to 5 doses |
| Placebo | Placebo comparator | Other: PlaceboMatching placebo, q12h for up to 5 doses |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 3K3A-APCAlso: 3K3A-Activated Protein C3K3A-APC, diluted in 0.9% sodium chloride in water, given at 100 mL IV infusion | Biological | 10mg of 3K3A-APC, 15mg of 3K3A-APC, 30mg of 3K3A-APC |
| PlaceboAlso: Matching PlaceboMatching placebo, 0.9% sodium chloride in water, given at 100 mL IV infusion | Other | Placebo |
Primary outcome
To evaluate the effect of 3K3A-APC on 90-day disability
Time frame: Day 90 mRS
Day 90 mRS scores will be compared between groups using ordinal (shift) analysis
1 secondary outcome
To evaluate the safety of 3K3A-APC
Time frame: Baseline to Day 90
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick D Lyden, MD principal investigator
University of Southern California
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 3K3A-APC in people with Ischemic Stroke, run by ZZ Biotech, LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 1 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the effect of 3K3A-APC on 90-day disability (time frame: Day 90 mRS). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2024.