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 (DAISY)

Key Inclusion Criteria: 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. Key Exclusion Criteria: 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. 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.