Ischemic StrokePhase 2DAISYNCT05764122
A Study to Evaluate the Efficacy and Safety of BIIB131 for Participants With Ischemic Stroke Between 4.5 and 24 Hours After Last Known Well
A Phase 2 study testing BIIB131 in people with Ischemic Stroke, run by Biogen.
Trial summary
The primary objective of the study is to evaluate the effects of BIIB131 on arterial revascularization (Part 1) and to determine if BIIB131 improves functional outcome as measured by the Modified Rankin Scale (mRS) when compared with placebo following acute ischemic stroke (AIS) (Part 2). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Ischemic Stroke
- What is being tested?
- BIIB131
- 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
- 29 Mar 2024to 7 Jul 2025
- Phase
- Phase 2
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Symptomatic intracranial occlusion, based on computed tomography angiography (CTA) or magnetic resonance angiography (MRA), at one of the following locations: intracranial internal carotid, M1, M2 or distal branches of the middle cerebral artery (MCA), anterior cerebral artery (ACA), or posterior cerebral artery (PCA).
- A participant is also eligible for enrollment if baseline imaging reveals a perfusion lesion (Tmax>6s) volume ≥10 mL on CTP or magnetic resonance (MR) perfusion-weighted imaging (PWI) within the territory of the ACA segments, a non-dominant or co-dominant M2 MCA segment, or more distal MCA segments, or the PCA segments, even if the occlusion is not immediately identified on baseline CTA.
- Note: In both Part 1 and Part 2, up to 30% of total randomized participants with occlusion locations at internal carotid artery (ICA) or M1 will be enrolled.
- Able to be randomized with study treatment start within 4.5 to 24 hours of last known well in compliance with local or national guidelines for thrombolytic treatment. If a participant awakes with stroke symptoms, they are eligible for enrollment if presentation and treatment start are within 24 hours of last known well.
- Pre-treatment score of NIHSS ≥5.
- Functionally independent prior to stroke onset as evidenced by premorbid mRS <3.
Who cannot join
- Large core infarction, evidenced by a core infarct volume >70 mL, assessed on DWI or CTP; or extensive early ischemic change (hypodensity) on noncontrast CT estimated to be >1/3 MCA territory, or significant hypodensity outside the Tmax>6s perfusion lesion that invalidates mismatch criteria.
- Occlusion in more than 1 vascular territory confirmed on CTA/MRA.
- Clinically significant cerebral edema per Investigator's judgement.
- Clinical suspicion or known history of any of the following
- Arterial dissection involving any intracranial artery or the aortic arch.
- Intracranial or intraspinal surgery within the 90 days prior to screening.
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- Intracranial hemorrhage.
- Imaging evidence, or signs and symptoms most consistent with subarachnoid hemorrhage.
- Cerebral infarction in the 90 days prior to screening.
- Septic embolus or concern for infective endocarditis.
- Prior thrombolytic administration within 90 days of screening.
- Prior treatment with BIIB131, any known history of systemic hypersensitivity reaction or anaphylaxis to BIIB131, the excipients contained in the formulation, and if applicable, any diagnostic agents anticipated to be administered during the study.
- NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
About this study
Official title: A Multicenter, Operationally Seamless, Double-Blind, Dose-Ranging, Placebo-Controlled, Randomized, Parallel-Group, Phase 2b Study to Evaluate the Efficacy and Safety of Intravenous BIIB131 for Participants With Ischemic Stroke Between 4.5 and 24 Hours After Last Known Well
The primary objective of the study is to evaluate the effects of BIIB131 on arterial revascularization (Part 1) and to determine if BIIB131 improves functional outcome as measured by the Modified Rankin Scale (mRS) when compared with placebo following acute ischemic stroke (AIS) (Part 2). The secondary objectives are to evaluate the effects of BIIB131 on angiographic reperfusion and infarct evolution, to determine if BIIB131 improves functional outcome, pharmacokinetic profile of BIIB131 (Part 1); to evaluate the effects of BIIB131 on acute and 90-day clinical outcomes (Part 2).
- Conditions
- Ischemic Stroke
- Being tested
- BIIB131, Placebo
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BIIB131Drug
Administered as specified in the treatment arm.
PlaceboDrug
Administered as specified in the treatment arm.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: BIIB131 Low Dose | Experimental | Participants will receive a single low dose of BIIB131 as an IV bolus followed by continuous IV infusion on Day 1. Based on the dose selection results from Part 1, participants may receive a single active dose of BIIB131 in Part 2. Receives: Drug: BIIB131 |
| Part 1: BIIB131 Medium Dose | Experimental | Participants will receive a single medium dose of BIIB131 as an IV bolus followed by continuous IV infusion on Day 1. Based on the dose selection results from Part 1, participants may receive a single active dose of BIIB131 in Part 2. Receives: Drug: BIIB131 |
| Part 1: BIIB131 High Dose | Experimental | Participants will receive a single high dose of BIIB131 as an IV bolus followed by continuous IV infusion on Day 1. Based on the dose selection results from Part 1, participants may receive a single active dose of BIIB131 in Part 2. Receives: Drug: BIIB131 |
| Part 1 and Part 2: Placebo | Placebo comparator | Participants will receive a single dose of BIIB131-matching placebo in Part 1 and Part 2, as an IV bolus followed by continuous IV infusion on Day 1. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part 1: Percentage of Participants with Arterial Revascularization
Revascularization of occluded intracranial arteries is defined by an arterial occlusive lesion (AOL) score of 2 or 3 on computed tomography angiography (CTA) or magnetic resonance angiography (MRA) at 4 ± 2 hours after treatment completion OR at the time of first digital subtraction angiography (DSA) acquisition in participants undergoing endovascular therapy (EVT).
Measured: Up to 6 hours
Part 1: Percentage of Participants with Reperfusion of the Ischemic Field
For participants with no visible intracranial occlusion on CT angiography at baseline, >90% reversal of the baseline Tmax>6s lesion at 4 ± 2 hours after treatment completion.
Measured: Up to 6 hours
Part 2: Ordinal Modified Ranking Scale (mRS) Score Based on a 6-Point Ordinal Scale
The mRS is a scale from 0 to 6, with 0 corresponding to no symptoms and 5/6 corresponding to worst outcome.
Measured: Day 90
Secondary outcomes (17)
Part 1: Percentage of Participants with an Expanded Thrombolysis in Cerebral Infarction (eTICI) Score = 2b50-3 (Complete or Partial Angiographic Reperfusion)
Measured: Up to 6 hours
Part 1: Percentage of Participants with an eTICI Score = 2c-3
Measured: Up to 6 hours
Part 1: Percentage of Penumbral Tissue Salvaged (Nonprogression to Infarction)
Measured: 24 hours
Part 1: Final Infarct Volume by Magnetic Resonance Imaging (MRI) or Noncontrast Computed Tomography (NCCT)
Measured: 24 hours
Part 1: Ordinal mRS Score Based on a 6-Point Ordinal Scale
The mRS consists of 7 grades, from 0 to 6, with 0 corresponding to no symptoms and 6 corresponding to death.
Measured: Day 90
Part 1: Concentration of BIIB131 in Plasma
Measured: Pre-dose and at multiple timepoints up to 24 hours post-dose
Part 2: Percentage of Participants with Improvement on the NIHSS by >5 Points or Score 0 or 1
The NIHSS is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0. Score 0 means no stroke symptoms. Score 1-4 means minor stroke. Score 5-15 means moderate stroke. Score 16-20 means moderate to severe stroke. Score 21-42 means severe stroke.
Measured: 24 hours
Parts 1 and 2: Percentage of Participants with Functional Independence (mRS Score 0-2)
Measured: 90 days
Parts 1 and 2: Percentage of Participants with no or Minimal Symptoms (mRS Score 0-1)
Measured: 90 days
Parts 1 and 2: Percentage of Participants with Barthel Index Score (BIS) >90
Measured: 90 days
Parts 1 and 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. SAE is any untoward medical occurrence that at any dose results in death, in the view of the investigator, places the participant at immediate risk of death (a life-threatening event), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect or is a medically important event.
Measured: Up to Day 90
Parts 1 and 2: Number of Participants with Symptomatic Intracranial Hemorrhage, Subarachnoid Hemorrhage, and/or Intraventricular Hemorrhage
Symptomatic intracranial hemorrhage is defined as local or remote parenchymal hemorrhage type 2, combined with a neurological deterioration of 4 points or more on the NIHSS from baseline (the closest collection before administration of the study treatment), or from the lowest NIHSS value between baseline and 24 hours, or leading to death.
Measured: Up to 36 hours post-randomization
Parts 1 and 2: Number of Participants with Any Intracranial Hemorrhage
Measured: Up to 14 days
Parts 1 and 2: Number of Participants with Major Bleeding
Measured: Up to 14 days
Parts 1 and 2: Number of Participants with Symptomatic Cerebral Edema
Measured: Up to 14 days
Parts 1 and 2: Percentage of Participants with Parenchymal Hematoma Type 2 Based on Heidelberg Bleeding Classification
Measured: Up to 7 days
Parts 1 and 2: Percentage of Participants with Parenchymal Hematoma Type 1 or 2 Based on Heidelberg Bleeding Classification
Measured: Up to 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2023
- Study start29 Mar 2024 (estimated)
- Primary completion7 Jul 2025 (estimated)
- Study completion7 Jul 2025 (estimated)
Why it stopped: Sponsor decision
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.
- More trials run by BiogenThe sponsor's other registered studies.
- 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 2
- 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
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Biogen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05764122
- Sponsor's protocol ID
- 289IS201
- Other IDs
- 2022-502364-20-00
- Acronym
- DAISY
- Status last verified
- Feb 2024
- First submitted
- 28 Feb 2023
- Last updated
- 12 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Operationally Seamless, Double-Blind, Dose-Ranging, Placebo-Controlled, Randomized, Parallel-Group, Phase 2b Study to Evaluate the Efficacy and Safety of Intravenous BIIB131 for Participants With Ischemic Stroke Between 4.5 and 24 Hours After Last Known Well
- ClinicalTrials.gov ID
- NCT05764122
- Acronym / sponsor ID
- DAISY / 289IS201
- Conditions
- Ischemic Stroke
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- 29 Mar 2024 (estimated)
- Primary completion
- 7 Jul 2025 (estimated)
- Study completion
- 7 Jul 2025 (estimated)
- First posted
- 10 Mar 2023 (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 primary objective of the study is to evaluate the effects of BIIB131 on arterial revascularization (Part 1) and to determine if BIIB131 improves functional outcome as measured by the Modified Rankin Scale (mRS) when compared with placebo following acute ischemic stroke (AIS) (Part 2). The secondary objectives are to evaluate the effects of BIIB131 on angiographic reperfusion and infarct evolution, to determine if BIIB131 improves functional outcome, pharmacokinetic profile of BIIB131 (Part 1); to evaluate the effects of BIIB131 on acute and 90-day clinical outcomes (Part 2).
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 |
|---|---|---|
| Part 1: BIIB131 Low Dose | Experimental | Drug: BIIB131Participants will receive a single low dose of BIIB131 as an IV bolus followed by continuous IV infusion on Day 1. Based on the dose selection results from Part 1, participants may receive a single active dose of BIIB131 in Part 2. |
| Part 1: BIIB131 Medium Dose | Experimental | Drug: BIIB131Participants will receive a single medium dose of BIIB131 as an IV bolus followed by continuous IV infusion on Day 1. Based on the dose selection results from Part 1, participants may receive a single active dose of BIIB131 in Part 2. |
| Part 1: BIIB131 High Dose | Experimental | Drug: BIIB131Participants will receive a single high dose of BIIB131 as an IV bolus followed by continuous IV infusion on Day 1. Based on the dose selection results from Part 1, participants may receive a single active dose of BIIB131 in Part 2. |
| Part 1 and Part 2: Placebo | Placebo comparator | Drug: PlaceboParticipants will receive a single dose of BIIB131-matching placebo in Part 1 and Part 2, as an IV bolus followed by continuous IV infusion on Day 1. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Symptomatic intracranial occlusion, based on computed tomography angiography (CTA) or magnetic resonance angiography (MRA), at one of the following locations: intracranial internal carotid, M1, M2 or distal branches of the middle cerebral artery (MCA), anterior cerebral artery (ACA), or posterior cerebral artery (PCA).
- A participant is also eligible for enrollment if baseline imaging reveals a perfusion lesion (Tmax>6s) volume ≥10 mL on CTP or magnetic resonance (MR) perfusion-weighted imaging (PWI) within the territory of the ACA segments, a non-dominant or co-dominant M2 MCA segment, or more distal MCA segments, or the PCA segments, even if the occlusion is not immediately identified on baseline CTA.
- Note: In both Part 1 and Part 2, up to 30% of total randomized participants with occlusion locations at internal carotid artery (ICA) or M1 will be enrolled.
- Able to be randomized with study treatment start within 4.5 to 24 hours of last known well in compliance with local or national guidelines for thrombolytic treatment. If a participant awakes with stroke symptoms, they are eligible for enrollment if presentation and treatment start are within 24 hours of last known well.
- Pre-treatment score of NIHSS ≥5.
Key exclusion criteria (13 listed)
- Large core infarction, evidenced by a core infarct volume >70 mL, assessed on DWI or CTP; or extensive early ischemic change (hypodensity) on noncontrast CT estimated to be >1/3 MCA territory, or significant hypodensity outside the Tmax>6s perfusion lesion that invalidates mismatch criteria.
- Occlusion in more than 1 vascular territory confirmed on CTA/MRA.
- Clinically significant cerebral edema per Investigator's judgement.
- Clinical suspicion or known history of any of the following
- Prior thrombolytic administration within 90 days of screening.
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 |
|---|---|---|
| BIIB131Administered as specified in the treatment arm. | Drug | Part 1: BIIB131 High Dose, Part 1: BIIB131 Low Dose, Part 1: BIIB131 Medium Dose |
| PlaceboAdministered as specified in the treatment arm. | Drug | Part 1 and Part 2: Placebo |
Primary outcome
Part 1: Percentage of Participants with Arterial Revascularization
Time frame: Up to 6 hours
Revascularization of occluded intracranial arteries is defined by an arterial occlusive lesion (AOL) score of 2 or 3 on computed tomography angiography (CTA) or magnetic resonance angiography (MRA) at 4 ± 2 hours after treatment completion OR at the time of first digital subtraction angiography (DSA) acquisition in participants undergoing endovascular therapy (EVT).
Part 1: Percentage of Participants with Reperfusion of the Ischemic Field
Time frame: Up to 6 hours
For participants with no visible intracranial occlusion on CT angiography at baseline, >90% reversal of the baseline Tmax>6s lesion at 4 ± 2 hours after treatment completion.
Part 2: Ordinal Modified Ranking Scale (mRS) Score Based on a 6-Point Ordinal Scale
Time frame: Day 90
The mRS is a scale from 0 to 6, with 0 corresponding to no symptoms and 5/6 corresponding to worst outcome.
17 secondary outcomes
Part 1: Percentage of Participants with an Expanded Thrombolysis in Cerebral Infarction (eTICI) Score = 2b50-3 (Complete or Partial Angiographic Reperfusion)
Time frame: Up to 6 hours
Part 1: Percentage of Participants with an eTICI Score = 2c-3
Time frame: Up to 6 hours
Part 1: Percentage of Penumbral Tissue Salvaged (Nonprogression to Infarction)
Time frame: 24 hours
Part 1: Final Infarct Volume by Magnetic Resonance Imaging (MRI) or Noncontrast Computed Tomography (NCCT)
Time frame: 24 hours
Part 1: Ordinal mRS Score Based on a 6-Point Ordinal Scale
Time frame: Day 90
Part 1: Concentration of BIIB131 in Plasma
Time frame: Pre-dose and at multiple timepoints up to 24 hours post-dose
Part 2: Percentage of Participants with Improvement on the NIHSS by >5 Points or Score 0 or 1
Time frame: 24 hours
Parts 1 and 2: Percentage of Participants with Functional Independence (mRS Score 0-2)
Time frame: 90 days
Parts 1 and 2: Percentage of Participants with no or Minimal Symptoms (mRS Score 0-1)
Time frame: 90 days
Parts 1 and 2: Percentage of Participants with Barthel Index Score (BIS) >90
Time frame: 90 days
Parts 1 and 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to Day 90
Parts 1 and 2: Number of Participants with Symptomatic Intracranial Hemorrhage, Subarachnoid Hemorrhage, and/or Intraventricular Hemorrhage
Time frame: Up to 36 hours post-randomization
Parts 1 and 2: Number of Participants with Any Intracranial Hemorrhage
Time frame: Up to 14 days
Parts 1 and 2: Number of Participants with Major Bleeding
Time frame: Up to 14 days
Parts 1 and 2: Number of Participants with Symptomatic Cerebral Edema
Time frame: Up to 14 days
Parts 1 and 2: Percentage of Participants with Parenchymal Hematoma Type 2 Based on Heidelberg Bleeding Classification
Time frame: Up to 7 days
Parts 1 and 2: Percentage of Participants with Parenchymal Hematoma Type 1 or 2 Based on Heidelberg Bleeding Classification
Time frame: Up to 7 days
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 12 Feb 2024.
- Individual participant dataSharing planned: Yes. In accordance with Biogen's Clinical Trial Transparency and Data Sharing Policy on https://www.biogentrialtransparency.com/
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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.
Medical Director study director
Biogen
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BIIB131 in people with Ischemic Stroke, run by Biogen.
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 6 inclusion and 13 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 12 Feb 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Part 1: Percentage of Participants with Arterial Revascularization (time frame: Up to 6 hours). The study lists 3 primary outcomes in all. 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 12 Feb 2024.