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

Primary Purpose

Acute Ischemic Stroke

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Balovaptan

Placebo

About this trial

This is an interventional treatment trial for Acute Ischemic Stroke

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

CPMC Comprehensive Stroke Care Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Balovaptan

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Percentage of Participants with modified Rankin Scale-Structured Interview (mRS-SI) score </= 4 vs. >4

Amount of MLS

MLS will be measured in millimeter on NCCT

Percentage of Participants with Surgical DHC Performed

Percentage of Participants Who Received Hyperosmolar therapy following initiation of study treatment

National Institute of Health Stroke Scale (NIHSS) score

Mortality

Mortality in the first 30 days after the enrollment

mRS-SI score

Functional Independence Measure (FIM) score

Glasgow Outcome Scale Extended (GOSE) Score

Stroke Impact Scale-16 (SIS-16) score

Length (in days) of ICU and Hospital Stay

Number of participants with adverse events and severity of adverse events

Severity will be determined according to the NCI CTCAE v5.0

Plasma concentrations of balovaptan at specified timepoints

Area under the concentration-time curve from Time 0 to 24 hours after a given dose (AUC24hr)

As calculated by NCA from measured concentration

Maximum observed concentration (Cmax)

As calculated by NCA or taken directly from measured concentration

Plasma drug concentration 24hours after the administration of a given dose (C24hr)

As calculated by NCA or taken directly from measured concentration

Number of participants with safety findings on brain imaging

Full Information

NCT ID

NCT05399550

First Posted

May 27, 2022

Last Updated

August 3, 2023

Sponsor

Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT05399550

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Withdrawn

Why Stopped

Sponsor's decision

Study Start Date

June 22, 2022 (Actual)

Primary Completion Date

November 17, 2022 (Actual)

Study Completion Date

November 17, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Ischemic Stroke

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Balovaptan

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Balovaptan

Intervention Description

Intravenous Solution

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Matching Intravenous Solution

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

72 Hours from Last Known Well

Secondary Outcome Measure Information:

Title

Percentage of Participants with modified Rankin Scale-Structured Interview (mRS-SI) score </= 4 vs. >4

Time Frame

At Day 90

Title

Amount of MLS

Description

MLS will be measured in millimeter on NCCT

Time Frame

At 48 hours and 96-120 hours from LKW

Title

Percentage of Participants with Surgical DHC Performed

Time Frame

From Baseline up to Day 90

Title

Percentage of Participants Who Received Hyperosmolar therapy following initiation of study treatment

Time Frame

From Baseline up to Day 90

Title

National Institute of Health Stroke Scale (NIHSS) score

Time Frame

At Day 4 and Day 90

Title

Mortality

Description

Mortality in the first 30 days after the enrollment

Time Frame

At Day 30

Title

mRS-SI score

Time Frame

At Day 30

Title

Functional Independence Measure (FIM) score

Time Frame

At Discharge or Day 10 and Day 90

Title

Glasgow Outcome Scale Extended (GOSE) Score

Time Frame

at Discharge or Day 10, Day 30 and Day 90

Title

Stroke Impact Scale-16 (SIS-16) score

Time Frame

At Day 30 and Day 90

Title

Length (in days) of ICU and Hospital Stay

Time Frame

From Baseline to Day 90

Title

Number of participants with adverse events and severity of adverse events

Description

Severity will be determined according to the NCI CTCAE v5.0

Time Frame

From Baseline to Day 90

Title

Plasma concentrations of balovaptan at specified timepoints

Time Frame

From Baseline to 120 Hours After the End of the Last Infusion (or at discharge)

Title

Area under the concentration-time curve from Time 0 to 24 hours after a given dose (AUC24hr)

Description

As calculated by NCA from measured concentration

Time Frame

From Baseline to 120 Hours After the End of the Last Infusion (or at discharge)]

Title

Maximum observed concentration (Cmax)

Description

As calculated by NCA or taken directly from measured concentration

Time Frame

From Baseline to 120 Hours After the End of the Last Infusion (or at discharge)]

Title

Plasma drug concentration 24hours after the administration of a given dose (C24hr)

Description

As calculated by NCA or taken directly from measured concentration

Time Frame

From Baseline to 120 Hours After the End of the Last Infusion (or at discharge)]

Title

Number of participants with safety findings on brain imaging

Time Frame

From Baseline to Day 90

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Trials

Organizational Affiliation

Hoffmann-La Roche

Official's Role

Study Director

Facility Information:

Facility Name

CPMC Comprehensive Stroke Care Center

City

San Francisco

State/Province

California

ZIP/Postal Code

94114

Country

United States

12. IPD Sharing Statement

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

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