Study to Evaluate The Safety and Efficacy of Balovaptan in Participants With Acute Ischemic Stroke at a 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Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05399550
• Other study ID #: WC 42759
• Status: Withdrawn
• Phase: Phase 2
• Start date: June 22, 2022
• Est. completion date: November 17, 2022

Study information

• Verified date: August 2023
• 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• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 17, 2022
• Est. primary completion date: November 17, 2022
• 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 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

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
United States	CPMC Comprehensive Stroke Care Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

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 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	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 Discharge or Day 10 and Day 90
Secondary	Glasgow Outcome Scale Extended (GOSE) Score		at Discharge or Day 10, Day 30 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