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

Acute Ischemic Stroke Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05310630
• Other study ID #: WC42759
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: March 31, 2022
• Est. completion date: June 27, 2024

Study information

• Verified date: April 2022
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 108
• Est. completion date: June 27, 2024
• Est. primary completion date: June 27, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

• NIHSS >15 for the non-dominant hemisphere and >20 for the dominant hemisphere

• 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 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

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Drug:
• Balovaptan
Intravenous Solution
• Placebo
Matching Intravenous Solution

Locations

Country	Name	City	State
France	CHU de Besancon Hopital Jean Minjoz; Service de Neurologie	Besançon
France	Groupe Hospitalier Paris Saint Joseph; Service de Neurologie et Neurovasculaire	Paris
France	CHU Poitiers - La Milétrie; Neurologie	Poitiers
Italy	Ospedale Santa Maria della Misericordia; Medicina Interna Vascolare d'Urgenza - Stroke Unit	Perugia	Umbria
Italy	Policlinico Umberto I; Unita` Trattamento Neurovascolare	Roma	Lazio
Italy	IRCCS Humanitas Research Hospital; Sezione Autonoma di Neurologia d'Urgenza e Stroke Unit	Rozzano (MI)	Lombardia
Spain	Hospital del Mar; Servicio de Neurologia	Barcelona
Spain	Universitario de La Princesa; Servicio de Neurología	Madrid
Spain	Hospital Virgen del Rocío; Servicio de Neurología	Sevilla
United Kingdom	Manchester Royal Infirmary	Manchester
United Kingdom	John Radcliffe Hospital; Acute Vascular Imaging Centre	Southampton
United Kingdom	University Hospital Southampton NHS Foundation Trust; Department of Stroke Medicine	Southampton
United States	University of Alabama At Birmingham	Birmingham	Alabama
United States	NYU Langone Hospital-Brooklyn	Brooklyn	New York
United States	UNC Chapel Hill	Chapel Hill	North Carolina
United States	Novant Health Presbyterain Medical Center	Charlotte	North Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Washington Regional Medical Center	Fayetteville	Arkansas
United States	McLaren Regional Medical Center	Flint	Michigan
United States	Hartford Hospital	Hartford	Connecticut
United States	Memorial Hermann Medical Plaza	Houston	Texas
United States	Baptist Medical Center - Jacksonville	Jacksonville	Florida
United States	Mayo Clinic in Florida; Neurology	Jacksonville	Florida
United States	Baptist Health Lexington	Lexington	Kentucky
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Baptist Hospital of Miami	Miami	Florida
United States	Aurora St. Luke's Medical Center	Milwaukee	Wisconsin
United States	West Virginia University Hospital	Morgantown	West Virginia
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Mount Sinai Hospital	New York	New York
United States	OU Health - University of Oklahoma Medical Center	Oklahoma City	Oklahoma
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Oregon Health & Science Uni	Portland	Oregon
United States	Mayo Clinic - Rochester;Department of Neurology	Rochester	Minnesota
United States	Barnes-Jewish Hospital , Washington University School of Medicine	Saint Louis	Missouri
United States	California Pacific Medical Center - Davies Campus	San Francisco	California
United States	California Pacific Medical Center - Van Ness Campus MOB	San Francisco	California
United States	Sarasota Memorial Hospital	Sarasota	Florida
United States	Bob Bove Neuroscience Institute	Scottsdale	Arizona
United States	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina
United States	Advent Health Orlando	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  France,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage of Participants with modified Rankin Scale-Structured Interview (mRS-SI) score </= 4 vs. >4		At Day 90
Secondary	Amount (in millimeters) of MLS	MLS will be measured in millimeter on NCCT	At 48 hours and 96-120 hours from LKW
Secondary	Percentage of Participants with Surgical DHC Performed		From Baseline up to Day 90
Secondary	Percentage of Participants Who Received Hyperosmolar therapy following initiation of study treatment		From Baseline up to Day 90
Secondary	Glasgow Coma Scale (GCS) Score		From Baseline up to Day 4
Secondary	National Institute of Health Stroke Scale (NIHSS) score		At Day 4 and Day 90
Secondary	Mortality	Mortality in the first 30 days after the enrollment	At Day 30
Secondary	mRS-SI score		At Day 30
Secondary	Functional Independence Measure (FIM) score		At Hospital Discharge or Day 10 and Day 90
Secondary	Stroke Impact Scale-16 (SIS-16) score		At Day 30 and Day 90
Secondary	Length (in days) of ICU and Hospital Stay		From Baseline to Day 90
Secondary	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
Secondary	Plasma concentrations of balovaptan at specified timepoints		From Baseline to 120 Hours After the End of the Last Infusion (or at discharge)
Secondary	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)]
Secondary	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)]
Secondary	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)]
Secondary	Number of participants with safety findings on brain imaging		From Baseline to Day 90