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

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05310630
Collaborator
(none)
108
Enrollment
44
Locations
2
Arms
26.9
Anticipated Duration (Months)
2.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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)

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
108 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Anticipated Study Start Date :
Mar 31, 2022
Anticipated Primary Completion Date :
Jun 27, 2024
Anticipated Study Completion Date :
Jun 27, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Amount of midline shift (MLS) at 72 hours from Last Known Well (LKW) [72 Hours from Last Known Well]

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

Secondary Outcome Measures

  1. Percentage of Participants with modified Rankin Scale-Structured Interview (mRS-SI) score </= 4 vs. >4 [At Day 90]

  2. Amount (in millimeters) of MLS [At 48 hours and 96-120 hours from LKW]

    MLS will be measured in millimeter on NCCT

  3. Percentage of Participants with Surgical DHC Performed [From Baseline up to Day 90]

  4. Percentage of Participants Who Received Hyperosmolar therapy following initiation of study treatment [From Baseline up to Day 90]

  5. Glasgow Coma Scale (GCS) Score [From Baseline up to Day 4]

  6. National Institute of Health Stroke Scale (NIHSS) score [At Day 4 and Day 90]

  7. Mortality [At Day 30]

    Mortality in the first 30 days after the enrollment

  8. mRS-SI score [At Day 30]

  9. Functional Independence Measure (FIM) score [At Hospital Discharge or Day 10 and Day 90]

  10. Stroke Impact Scale-16 (SIS-16) score [At Day 30 and Day 90]

  11. Length (in days) of ICU and Hospital Stay [From Baseline to Day 90]

  12. Number of participants with adverse events and severity of adverse events [From Baseline to Day 90]

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

  13. Plasma concentrations of balovaptan at specified timepoints [From Baseline to 120 Hours After the End of the Last Infusion (or at discharge)]

  14. Area under the concentration-time curve from Time 0 to 24 hours after a given dose (AUC24hr) [From Baseline to 120 Hours After the End of the Last Infusion (or at discharge)]]

    As calculated by NCA from measured concentration

  15. Maximum observed concentration (Cmax) [From Baseline to 120 Hours After the End of the Last Infusion (or at discharge)]]

    As calculated by NCA or taken directly from measured concentration

  16. Plasma drug concentration 24hours after the administration of a given dose (C24hr) [From Baseline to 120 Hours After the End of the Last Infusion (or at discharge)]]

    As calculated by NCA or taken directly from measured concentration

  17. Number of participants with safety findings on brain imaging [From Baseline to Day 90]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of Alabama At Birmingham Birmingham Alabama United States 35294
2 Bob Bove Neuroscience Institute Scottsdale Arizona United States 85251
3 Washington Regional Medical Center Fayetteville Arkansas United States 72703
4 Cedars Sinai Medical Center Los Angeles California United States 90048
5 California Pacific Medical Center - Van Ness Campus MOB San Francisco California United States 94109
6 California Pacific Medical Center - Davies Campus San Francisco California United States 94114
7 Hartford Hospital Hartford Connecticut United States 06102
8 Baptist Medical Center - Jacksonville Jacksonville Florida United States 32207-8202
9 Mayo Clinic in Florida; Neurology Jacksonville Florida United States 32224
10 Baptist Hospital of Miami Miami Florida United States 33176
11 Sarasota Memorial Hospital Sarasota Florida United States 34239
12 Advent Health Orlando Winter Park Florida United States 32789
13 Northwestern Memorial Hospital Chicago Illinois United States 60611
14 Baptist Health Lexington Lexington Kentucky United States 40503
15 McLaren Regional Medical Center Flint Michigan United States 48532
16 Mayo Clinic - Rochester;Department of Neurology Rochester Minnesota United States 55904
17 Barnes-Jewish Hospital , Washington University School of Medicine Saint Louis Missouri United States 63110
18 NYU Langone Hospital-Brooklyn Brooklyn New York United States 11220
19 Mount Sinai Hospital New York New York United States 10128
20 UNC Chapel Hill Chapel Hill North Carolina United States 27514
21 Novant Health Presbyterain Medical Center Charlotte North Carolina United States 28204
22 Novant Health Forsyth Medical Center Winston-Salem North Carolina United States 27103
23 Riverside Methodist Hospital Columbus Ohio United States 43214
24 OU Health - University of Oklahoma Medical Center Oklahoma City Oklahoma United States 73104
25 Oregon Health & Science Uni Portland Oregon United States 97239
26 Thomas Jefferson University Philadelphia Pennsylvania United States 19107
27 Vanderbilt University Medical Center Nashville Tennessee United States 37232
28 UT Southwestern Medical Center Dallas Texas United States 75390-8813
29 Memorial Hermann Medical Plaza Houston Texas United States 77030
30 University of Virginia Health System Charlottesville Virginia United States 22903
31 West Virginia University Hospital Morgantown West Virginia United States 26506
32 Aurora St. Luke's Medical Center Milwaukee Wisconsin United States 53215
33 CHU de Besancon Hopital Jean Minjoz; Service de Neurologie Besançon France 25030
34 Groupe Hospitalier Paris Saint Joseph; Service de Neurologie et Neurovasculaire Paris France 75014
35 CHU Poitiers - La Milétrie; Neurologie Poitiers France 86021
36 Policlinico Umberto I; Unità Trattamento Neurovascolare Roma Lazio Italy 00161
37 IRCCS Humanitas Research Hospital; Sezione Autonoma di Neurologia d'Urgenza e Stroke Unit Rozzano (MI) Lombardia Italy 20089
38 Ospedale Santa Maria della Misericordia; Medicina Interna Vascolare d'Urgenza - Stroke Unit Perugia Umbria Italy 06129
39 Hospital del Mar; Servicio de Neurologia Barcelona Spain 08003
40 Universitario de La Princesa; Servicio de Neurología Madrid Spain 28006
41 Hospital Virgen del Rocío; Servicio de Neurología Sevilla Spain 41013
42 Manchester Royal Infirmary Manchester United Kingdom M13 9WL
43 John Radcliffe Hospital; Acute Vascular Imaging Centre Southampton United Kingdom OX3 9DU
44 University Hospital Southampton NHS Foundation Trust; Department of Stroke Medicine Southampton United Kingdom SO16 6YD

Sponsors and Collaborators

  • Hoffmann-La Roche

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT05310630
Other Study ID Numbers:
  • WC42759
First Posted:
Apr 5, 2022
Last Update Posted:
Apr 5, 2022
Last Verified:
Apr 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Stroke
Ischemic Stroke
Cerebral Infarction
Ischemia

Study Results

No Results Posted as of Apr 5, 2022