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

NCT05764122 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 289IS2012022-502364-20-00
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Ischemic Stroke

Outcome Measures

Primary Outcomes (3)

• 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).

  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.

  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.

  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)

  Up to 6 hours

• Part 1: Percentage of Participants with an eTICI Score = 2c-3

  Up to 6 hours

• Part 1: Percentage of Penumbral Tissue Salvaged (Nonprogression to Infarction)

  24 hours

• Part 1: Final Infarct Volume by Magnetic Resonance Imaging (MRI) or Noncontrast Computed Tomography (NCCT)

  24 hours

• Part 1: Ordinal mRS Score Based on a 6-Point Ordinal Scale

  Day 90

Study Arms (4)

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.

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.

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.

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.

Drug: Placebo

Interventions

BIIB131 DRUG

Administered as specified in the treatment arm.

Part 1: BIIB131 High Dose; Part 1: BIIB131 Low Dose; Part 1: BIIB131 Medium Dose

Placebo DRUG

Administered as specified in the treatment arm.

Part 1 and Part 2: Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biogen: lead

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2023
• First Posted: March 10, 2023
• Study Start: March 29, 2024
• Primary Completion: July 7, 2025
• Study Completion: July 7, 2025
• Last Updated: February 12, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share