Study to Evaluate The Safety and Efficacy of Balovaptan in Participants With Acute Ischemic Stroke at a High Risk of Developing Malignant Brain Edema

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

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)

Study Overview

• Status: Withdrawn
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Balovaptan; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94114
      • CPMC Comprehensive Stroke Care Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Balovaptan; Balovaptan will be administered as IV infusion once a day over 3 days	Drug: Balovaptan; Intravenous Solution
Placebo Comparator: Placebo; Placebo will be administered as IV infusion once a day over 3 days	Drug: Placebo; Matching Intravenous Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of midline shift (MLS) at 72 hours from Last Known Well (LKW)	Midline shift will be measured in millimeter on non-contrast computer tomography (NCCT)	72 Hours from Last Known Well

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with modified Rankin Scale-Structured Interview (mRS-SI) score </= 4 vs. >4		At Day 90
Amount of MLS	MLS will be measured in millimeter on NCCT	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
Mortality	Mortality in the first 30 days after the enrollment	At Day 30
mRS-SI score		At Day 30
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	Severity will be determined according to the NCI CTCAE v5.0	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)	As calculated by NCA from measured concentration	From Baseline to 120 Hours After the End of the Last Infusion (or at discharge)]
Maximum observed concentration (Cmax)	As calculated by NCA or taken directly from measured concentration	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)	As calculated by NCA or taken directly from measured concentration	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2022
• Primary Completion (Actual): November 17, 2022
• Study Completion (Actual): November 17, 2022

Study Registration Dates

• First Submitted: May 27, 2022
• First Submitted That Met QC Criteria: May 27, 2022
• First Posted (Actual): June 1, 2022

Study Record Updates

• Last Update Posted (Actual): August 7, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Antidiuretic Hormone Receptor Antagonists; Balovaptan
• Other Study ID Numbers: WC 42759

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No