A Study to Evaluate the Safety and Ability of Balovaptan to Reduce the Risk of Severe Brain Swelling in Patients with Acute Ischemic Stroke

Phase 1

• Conditions: Acute Ischemic Stroke (AIS); MedDRA version: 20.0Level: LLTClassification code 10008107Term: Cerebral edemaSystem Organ Class: 100000004852; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2021-002076-39-ES
• Lead Sponsor: Roche Farma S. A. U. que realiza el ensayo en España y que actúa como representante F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-01-03
• Last Update Posted: 26 September 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 108

Inclusion Criteria

? Participants who are between the ages >=18 and <=80 years at the time of signing Informed Consent Form
? Diagnosis of large vessel occlusion (LVO) in the anterior circulation such that study drug administration can be initiated within 12 hours of last known well (LKW) and at risk of malignant cerebral edema (MCE) development, as defined as follows: Documented occlusion of terminus ICA and/or MCA on CTA or magnetic resonance angiogram AND ASPECTS score <= 5 AND National Institutes of Health Stroke Scale (NIHSS) > 15 for the non-dominant hemisphere and > 20 for the dominant hemisphere
? Participants who present with a wake-up stroke (WUS) who are <=8 hours from awakening
? 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 agreement to remain abstinent or use contraception and agree to refrain from donating eggs, during the treatment period and for at least 28 days after the final dose of balovaptan
? No specific contraception methods for males are required
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 49
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 59

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 parenchymatous hematoma ([PH]1 or PH2) on baseline imaging (per Heidelberg classification)
? 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
? Diagnosis of diabetes insipidus
? Participants who have received any prophylactic hyperosmolar therapy
? Participants who have received treatment with any other V1a and/or V2 receptor-blocking agent or glyburide
? A preexisting medical condition for which the participant is unlikely to survive the next 6 months
? Planned limitation or withdrawal of life-sustaining treatment during hospital admission
? Participants who are pregnant or breastfeeding, or intending to become pregnant

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: ? To evaluate the efficacy of balovaptan compared with placebo based on the amount of midline shift (MLS);Secondary Objective: ? To evaluate the efficacy of balovaptan compared with placebo based on global disability, amount of MLS, proportion of patients with surgical decompressive hemicraniectomy (DHC), proportion of patients who received hyperosmolar therapy, impairment of consciousness, neurological impairment, mortality, functional independence, stroke disability and health-related quality of life, hospital length of stay and ICU length of stay<br>? To evaluate the safety of balovaptan compared with placebo<br>? To characterize the balovaptan, M2, and M3 pharmacokinetic (PK) profile;Primary end point(s): 1. Amount of MLS, as measured in millimeters at the level of the septum pellucidum on NCCT at 72 hours from LKW;Timepoint(s) of evaluation of this end point: 1. At 72 hours from LKW