Clinical trial NCT05764122: 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
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Ischemic Stroke
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2023-03-10
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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). 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).


Eligibility criteria: Key Inclusion Criteria:

1. 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.
2. 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.
3. Pre-treatment score of NIHSS ≥5.
4. Functionally independent prior to stroke onset as evidenced by premorbid mRS \<3.

Key Exclusion Criteria:

1. 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.
2. Occlusion in more than 1 vascular territory confirmed on CTA/MRA.
3. Clinically significant cerebral edema per Investigator's judgement.
4. Clinical suspicion or known history of any of the following

   1. Arterial dissection involving any intracranial artery or the aortic arch.
   2. Intracranial or intraspinal surgery within the 90 days prior to screening.
   3. Intracranial hemorrhage.
   4. Imaging evidence, or signs and symptoms most consistent with subarachnoid hemorrhage.
   5. Cerebral infarction in the 90 days prior to screening.
   6. Septic embolus or concern for infective endocarditis.
5. Prior thrombolytic administration within 90 days of screening.
6. 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.

Primary outcomes:
measure: Part 1: Percentage of Participants with Arterial Revascularization
timeFrame: Up to 6 hours
measure: Part 1: Percentage of Participants with Reperfusion of the Ischemic Field
timeFrame: Up to 6 hours
measure: Part 2: Ordinal Modified Ranking Scale (mRS) Score Based on a 6-Point Ordinal Scale
timeFrame: Day 90
Secondary outcomes:
measure: Part 1: Percentage of Participants with an Expanded Thrombolysis in Cerebral Infarction (eTICI) Score = 2b50-3 (Complete or Partial Angiographic Reperfusion)
timeFrame: Up to 6 hours
measure: Part 1: Percentage of Participants with an eTICI Score = 2c-3
timeFrame: Up to 6 hours
measure: Part 1: Percentage of Penumbral Tissue Salvaged (Nonprogression to Infarction)
timeFrame: 24 hours
measure: Part 1: Final Infarct Volume by Magnetic Resonance Imaging (MRI) or Noncontrast Computed Tomography (NCCT)
timeFrame: 24 hours
measure: Part 1: Ordinal mRS Score Based on a 6-Point Ordinal Scale
timeFrame: Day 90
measure: Part 1: Concentration of BIIB131 in Plasma
timeFrame: Pre-dose and at multiple timepoints up to 24 hours post-dose
measure: Part 2: Percentage of Participants with Improvement on the NIHSS by >5 Points or Score 0 or 1
timeFrame: 24 hours
measure: Parts 1 and 2: Percentage of Participants with Functional Independence (mRS Score 0-2)
timeFrame: 90 days
measure: Parts 1 and 2: Percentage of Participants with no or Minimal Symptoms (mRS Score 0-1)
timeFrame: 90 days
measure: Parts 1 and 2: Percentage of Participants with Barthel Index Score (BIS) >90
timeFrame: 90 days
measure: Parts 1 and 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Day 90
measure: Parts 1 and 2: Number of Participants with Symptomatic Intracranial Hemorrhage, Subarachnoid Hemorrhage, and/or Intraventricular Hemorrhage
timeFrame: Up to 36 hours post-randomization
measure: Parts 1 and 2: Number of Participants with Any Intracranial Hemorrhage
timeFrame: Up to 14 days
measure: Parts 1 and 2: Number of Participants with Major Bleeding
timeFrame: Up to 14 days
measure: Parts 1 and 2: Number of Participants with Symptomatic Cerebral Edema
timeFrame: Up to 14 days
measure: Parts 1 and 2: Percentage of Participants with Parenchymal Hematoma Type 2 Based on Heidelberg Bleeding Classification
timeFrame: Up to 7 days
measure: Parts 1 and 2: Percentage of Participants with Parenchymal Hematoma Type 1 or 2 Based on Heidelberg Bleeding Classification
timeFrame: Up to 7 days
Other outcomes:
Locations:
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: