A Phase II, Randomized, Double Blind, Placebo Controlled Multicenter Study to Evaluate The Safety and Efficacy of Balovaptan in Patients With Acute Ischemic Stroke at High Risk of Developing Malignant Cerebral Edema

Hoffmann-La Roche1 site in 1 countryJune 22, 2022

ConditionsAcute Ischemic Stroke

InterventionsBalovaptan Placebo

DrugsBalovaptan Placebo

Overview

Phase: Phase 2
Intervention: Balovaptan
Conditions: Acute Ischemic Stroke
Sponsor: Hoffmann-La Roche
Locations: 1
Primary Endpoint: Amount of midline shift (MLS) at 72 hours from Last Known Well (LKW)
Status: Withdrawn
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study is designed to evaluate the safety, efficacy, and pharmacokinetics of balovaptan compared with placebo in participants with acute ischemic stroke (AIS) at risk of developing Malignant Cerebral Edema (MCE)

Registry

clinicaltrials.gov

Start Date

June 22, 2022

End Date

November 17, 2022

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Diagnosis of LVO in the anterior circulation such that study drug administration can be initiated within 12 hours of LKW and at risk of MCE development, as defined as follows:
•Documented occlusion of terminus ICA and/or MCA on CTA or magnetic resonance angiogram and
•ASPECTS score \</=5 on NCCT and
•NIHSS \>15 for the non-dominant hemisphere and \>20 for the dominant hemisphere (or \> 20 if dominant/non-dominant hemisphere unknown)
•Present with a WUS \</=8 hours from awakening provided the above criteria are met
•Participants with a history of seizures on anti-epileptic medications may be included if they have been on stable doses of those medications for at least 12 weeks prior to LKW, they have not experienced seizures during that time frame, and their anti-epileptic medicines are continued during the study
•For women of childbearing potential: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use contraception and agree to refrain from donating eggs
•No specific contraception methods for males are required.

Exclusion Criteria

•Participants who are \>12 hours from LKW at the start of treatment with study drug or \>8 hours from awakening with WUS
•Any MLS on brain imaging
•Evidence of intracranial hemorrhage at screening based on NCCT
•Contraindication to MRI examination
•Evidence of additional anterior cerebral artery (ACA) infarction
•Diagnosis of brain death
•Planned surgical decompression prior to randomization
•Participants with a known history of a hereditary bleeding disorder which increases bleeding risk
•Chronic kidney disease stage III or higher
•Hepatic injury

Arms & Interventions

Balovaptan

Balovaptan will be administered as IV infusion once a day over 3 days

Intervention: Balovaptan

Placebo

Placebo will be administered as IV infusion once a day over 3 days

Intervention: Placebo

Outcomes

Primary Outcomes

Amount of midline shift (MLS) at 72 hours from Last Known Well (LKW)

Time Frame: 72 Hours from Last Known Well

Midline shift will be measured in millimeter on non-contrast computer tomography (NCCT)

Secondary Outcomes

Mortality(At Day 30)
mRS-SI score(At Day 30)
Amount of MLS(At 48 hours and 96-120 hours from LKW)
Percentage of Participants with Surgical DHC Performed(From Baseline up to Day 90)
Percentage of Participants Who Received Hyperosmolar therapy following initiation of study treatment(From Baseline up to Day 90)
National Institute of Health Stroke Scale (NIHSS) score(At Day 4 and Day 90)
Percentage of Participants with modified Rankin Scale-Structured Interview (mRS-SI) score </= 4 vs. >4(At Day 90)
Functional Independence Measure (FIM) score(At Discharge or Day 10 and Day 90)
Glasgow Outcome Scale Extended (GOSE) Score(at Discharge or Day 10, Day 30 and Day 90)
Stroke Impact Scale-16 (SIS-16) score(At Day 30 and Day 90)
Length (in days) of ICU and Hospital Stay(From Baseline to Day 90)
Number of participants with adverse events and severity of adverse events(From Baseline to Day 90)
Plasma concentrations of balovaptan at specified timepoints(From Baseline to 120 Hours After the End of the Last Infusion (or at discharge))
Area under the concentration-time curve from Time 0 to 24 hours after a given dose (AUC24hr)(From Baseline to 120 Hours After the End of the Last Infusion (or at discharge)])
Maximum observed concentration (Cmax)(From Baseline to 120 Hours After the End of the Last Infusion (or at discharge)])
Plasma drug concentration 24hours after the administration of a given dose (C24hr)(From Baseline to 120 Hours After the End of the Last Infusion (or at discharge)])
Number of participants with safety findings on brain imaging(From Baseline to Day 90)