A Study With SAGE-547 for Super-Refractory Status Epilepticus

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of SAGE-547 Injection in the Treatment of Subjects With Super-Refractory Status Epilepticus

This is a randomized, double-blind, placebo-controlled trial, designed to evaluate the efficacy and safety of SAGE-547 administered as a continuous intravenous infusion to subjects in Super-Refractory Status Epilepticus (SRSE).

Study Overview

• Status: Completed
• Conditions: Super-Refractory Status Epilepticus
• Intervention / Treatment: Drug: Placebo; Drug: SAGE-547

• Study Type: Interventional
• Enrollment (Actual): 132
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Sage Investigational Site
  • Salzburg, Austria, 5020
    • Sage Investigational Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H3V4
      • Sage Investigational Site
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Sage Investigational Site
    • Kingston, Ontario, Canada, K7L3C9
      • Sage Investigational Site
    • London, Ontario, Canada, N6A5A5
      • Sage Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Sage Investigational Site
    • Montreal, Quebec, Canada, H2L 4M1
      • Sage Investigational Site
    • Montreal, Quebec, Canada, H3A 2B4
      • Sage Investigational Site
    • Montreal, Quebec, Canada, H3T1C5
      • Sage Investigational Site
    • Montréal, Quebec, Canada, H1T 2M4
      • Sage Investigational Site
    • Montréal, Quebec, Canada, H3T 1C5
      • Sage Investigational Site
• Denmark
  • Copenhagen, Denmark, 2100
    • Sage Investigational Site
• Estonia
  • Tallinn, Estonia, 10617
    • Sage Investigational Site
  • Tallinn, Estonia, 13419
    • Sage Investigational Site
  • Tartu, Estonia, 51014
    • Sage Investigational Site
• Finland
  • Helsinki, Finland, 00029
    • Sage Investigational Site
  • Kuopio, Finland, 70210
    • Sage Investigational Site
• France
  • Bron Cedex, France, 69677
    • Sage Investigational Site
  • Dijon, France, 21079
    • Sage Investigational Site
  • Lille, France, 59037
    • Sage Investigational Site
  • Limoges, France, 87042
    • Sage Investigational Site
  • Lyon, France, 69677
    • Sage Investigational Site
  • Paris, France, 75851
    • Sage Investigational Site
• Germany
  • Hamburg, Germany, 22337
    • Sage Investigational Site
  • Marburg, Germany, 35043
    • Sage Investigational Site
  • Osnabruck, Germany, 49076
    • Sage Investigational Site
• Hungary
  • Balassagyarmat, Hungary, 2660
    • Sage Investigational Site
  • Budapest, Hungary, 01134
    • Sage Investigational Site
  • Budapest, Hungary, 1134
    • Sage Investigational Site
• Israel
  • Ashqelon, Israel, 7830604
    • Sage Investigational Site
  • Holon, Israel, 58100
    • Sage Investigational Site
  • Holon, Israel
    • Sage Investigational Site
  • Jerusalem, Israel, 91120
    • Sage Investigational Site
  • Petach Tikva, Israel, 49100
    • Sage Investigational Site
  • Tel Hashomer, Israel, 52621
    • Sage Investigational Site
  • Tzrifin, Israel, 70300
    • Sage Investigational Site
• Italy
  • Bologna, Italy, 40139
    • Sage Investigational Site
  • Firenze, Italy, 50139
    • Sage Investigational Site
  • Florence, Italy, 50139
    • Sage Investigational Site
  • Milan, Italy, 20132
    • Sage Investigational Site
  • Milano, Italy, 20132
    • Sage Investigational Site
  • Milano, Italy, 20133
    • Sage Investigational Site
  • Modena, Italy, 41100
    • Sage Investigational Site
  • Modena, Italy, 41126
    • Sage Investigational Site
  • Monza, Italy, 20900
    • Sage Investigational Site
  • Perugia, Italy, 06129
    • Sage Investigational Site
  • Reggio Calabria, Italy, 89124
    • Sage Investigational Site
  • Rome, Italy, 00165
    • Sage Investigational Site
  • Rome, Italy, 165
    • Sage Investigational Site
  • Verona, Italy, 37126
    • Sage Investigational Site
• Netherlands
  • Enschede, Netherlands, 7512KZ
    • Sage Investigational Site
  • Heerlen, Netherlands, 6419PC
    • Sage Investigational Site
  • Maastricht, Netherlands, 6202AZ
    • Sage Investigational Site
  • Nijmegen, Netherlands, 6525GA
    • Sage Investigational Site
• Serbia
  • Belgrade, Serbia, 11000
    • Sage Investigational Site
  • Belgrade, Serbia, 11070
    • Sage Investigational Site
  • Nis, Serbia, 18000
    • Sage Investigational Site
  • Novi Sad, Serbia, 21000
    • Sage Investigational Site
• Spain
  • Badalona, Spain, 8916
    • Sage Investigational Site
  • Barakaldo, Spain, 48903
    • Sage Investigational Site
  • Barcelona, Spain, 08035
    • Sage Investigational Site
  • Barcelona, Spain, 08036
    • Sage Investigational Site
  • Cordoba, Spain, 14004
    • Sage Investigational Site
  • Granada, Spain, 18016
    • Sage Investigational Site
  • Hospitalet de Llobregat, Spain, 08907
    • Sage Investigational Site
  • Madrid, Spain, 28040
    • Sage Investigational Site
• Sweden
  • Gothenburg, Sweden, 413 45
    • Sage Investigational Site
• United Kingdom
  • Manchester, United Kingdom, M6 8HD
    • Sage Investigational Site
  • Norfolk, United Kingdom, NR4 7UY
    • Sage Investigational Site
  • Norwich, United Kingdom, NR4 7UY
    • Sage Investigational Site
  • Staffordshire, United Kingdom, ST3 6QG
    • Sage Investigational Site
  • Stoke-on-Trent, United Kingdom, ST4 6QG
    • Sage Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Sage Investigational Site
    • Mobile, Alabama, United States, 36667
      • Sage Investigational Site
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Sage Investigational Site
    • Phoenix, Arizona, United States, 85013
      • Sage Investigational Site
  • Arkansas
    • Little Rock, Arkansas, United States, 27702
      • Sage Investigational Site
  • California
    • Fresno, California, United States, 93721
      • Sage Investigational Site
    • Loma Linda, California, United States, 92354
      • Sage Investigational Site
    • Los Angeles, California, United States, 90027
      • Sage Investigational Site
    • Roseville, California, United States, 95661
      • Sage Investigational Site
    • Sacramento, California, United States, 95317
      • Sage Investigational Site
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Sage Investigational Site
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Sage Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Sage Investigational Site
  • Florida
    • Gainesville, Florida, United States, 32611
      • Sage Investigational Site
    • Jacksonville, Florida, United States, 32209
      • Sage Investigational Site
    • Miami, Florida, United States, 33155
      • Sage Investigational Site
    • Orlando, Florida, United States, 32803
      • Sage Investigational Site
    • Sarasota, Florida, United States, 34239
      • Sage Investigational Site
    • Tampa, Florida, United States, 33613
      • Sage Investigational Site
    • Weston, Florida, United States, 33331
      • Sage Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Sage Investigational Site
    • Atlanta, Georgia, United States, 30303
      • Sage Investigational Site
    • Atlanta, Georgia, United States, 30322
      • Sage Investigational Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Sage Investigational Site
    • Honolulu, Hawaii, United States, 96826
      • Sage Investigational Site
  • Idaho
    • Boise, Idaho, United States, 83706
      • Sage Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Sage Investigational Site
    • Chicago, Illinois, United States, 60612
      • Sage Investigational Site
    • Maywood, Illinois, United States, 60153
      • Sage Investigational Site
    • Peoria, Illinois, United States, 61637
      • Sage Investigational Site
    • Springfield, Illinois, United States, 62702
      • Sage Investigational Site
    • Urbana, Illinois, United States, 61801
      • Sage Investigational Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Sage Investigational Site
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Sage Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Sage Investigational Site
    • Louisville, Kentucky, United States, 40202
      • Sage Investigational Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Sage Investigational Site
    • New Orleans, Louisiana, United States, 70115
      • Sage Investigational Site
  • Maine
    • Portland, Maine, United States, 04102
      • Sage Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Sage Investigational Site
    • Baltimore, Maryland, United States, 21215
      • Sage Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Sage Investigational Site
    • Boston, Massachusetts, United States, 02115
      • Sage Investigational Site
    • Boston, Massachusetts, United States, 02111
      • Sage Investigational Site
    • Boston, Massachusetts, United States, 02118
      • Sage Investigational Site
    • Boston, Massachusetts, United States, 02215
      • Sage Investigational Site
    • Newton, Massachusetts, United States, 02462
      • Sage Investigational Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Sage Investigational Site
    • Detroit, Michigan, United States, 48201
      • Sage Investigational Site
    • Detroit, Michigan, United States, 48202
      • Sage Investigational Site
    • East Lansing, Michigan, United States, 48824
      • Sage Investigational Site
    • Grand Rapids, Michigan, United States, 49503
      • Sage Investigational Site
    • Royal Oak, Michigan, United States, 48073
      • Sage Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • Sage Investigational Site
    • Rochester, Minnesota, United States, 55905
      • Sage Investigational Site
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Sage Investigational Site
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Sage Investigational Site
    • Saint Louis, Missouri, United States, 63110
      • Sage Investigational Site
  • New Jersey
    • Edison, New Jersey, United States, 08818
      • Sage Investigational Site
    • Morristown, New Jersey, United States, 08827
      • Sage Investigational Site
    • New Brunswick, New Jersey, United States, 08901
      • Sage Investigational Site
    • Summit, New Jersey, United States, 07901
      • Sage Investigational Site
  • New York
    • Buffalo, New York, United States, 14203
      • Sage Investigational Site
    • New York, New York, United States, 10032
      • Sage Investigational Site
    • New York, New York, United States, 10016
      • Sage Investigational Site
    • New York, New York, United States, 10029
      • Sage Investigational Site
    • Port Jefferson, New York, United States, 11777
      • Sage Investigational Site
    • Rochester, New York, United States, 14642
      • Sage Investigational Site
    • Syracuse, New York, United States, 13210
      • Sage Investigational Site
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Sage Investigational Site
    • Winston-Salem, North Carolina, United States, 27157
      • Sage Investigational Site
  • Ohio
    • Akron, Ohio, United States, 44308
      • Sage Investigational Site
    • Cincinnati, Ohio, United States, 45229
      • Sage Investigational Site
    • Cincinnati, Ohio, United States, 45267
      • Sage Investigational Site
    • Cleveland, Ohio, United States, 44195
      • Sage Investigational Site
    • Columbus, Ohio, United States, 43210
      • Sage Investigational Site
    • Toledo, Ohio, United States, 43614
      • Sage Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97213
      • Sage Investigational Site
    • Portland, Oregon, United States, 97225
      • Sage Investigational Site
    • Portland, Oregon, United States, 97239
      • Sage Investigational Site
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Sage Investigational Site
    • Philadelphia, Pennsylvania, United States, 19104
      • Sage Investigational Site
    • Philadelphia, Pennsylvania, United States, 19107
      • Sage Investigational Site
    • Philadelphia, Pennsylvania, United States, 19140
      • Sage Investigational Site
    • Philadelphia, Pennsylvania, United States, 19141
      • Sage Investigational Site
    • Philadelphia, Pennsylvania, United States, 19147
      • Sage Investigational Site
    • Pittsburgh, Pennsylvania, United States, 15212
      • Sage Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Sage Investigational Site
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Sage Investigational Site
    • Nashville, Tennessee, United States, 37232
      • Sage Investigational Site
  • Texas
    • Austin, Texas, United States, 78723
      • Sage Investigational Site
    • Dallas, Texas, United States, 75251
      • Sage Investigational Site
    • San Antonio, Texas, United States, 78229
      • Sage Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Sage Investigational Site
    • Salt Lake City, Utah, United States, 84113
      • Sage Investigational Site
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Sage Investigational Site
  • Washington
    • Seattle, Washington, United States, 98105
      • Sage Investigational Site
  • West Virginia
    • Huntington, West Virginia, United States, 25705
      • Sage Investigational Site
    • Morgantown, West Virginia, United States, 26506
      • Sage Investigational Site
  • Wisconsin
    • Wauwatosa, Wisconsin, United States, 53226
      • Sage Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects two (2) years of age and older

• Subjects who have:

  • Failed to respond to the administration of at least one first-line agent (e.g., benzodiazepine or other emergent initial anti-epileptic drug [AED] treatment), according to institution standard of care, and;
  • Failed to respond to at least one second-line agent (e.g., phenytoin, fosphenytoin, valproate, phenobarbital, levetiracetam or other urgent control AED), according to institution standard of care, and;
  • Not previously been administered a third-line agent but have been admitted to an intensive care unit with the intent of administering at least one third-line agent for at least 24 hours; or who have previously failed zero, one or more wean attempts from third-line agents and are now on continuous intravenous infusions of one or more third-line agent and in an EEG burst or seizure suppression pattern; or who have previously failed one or more wean attempts from third-line agents and are now either not on a continuous intravenous infusion of at least one third-line agent or are on a continuous intravenous infusion of one or more third-line agent but not in an EEG burst or seizure suppression pattern

Exclusion Criteria:

• Subjects with SRSE due to anoxic/hypoxic encephalopathy with highly malignant/ malignant EEG features
• Children (subjects aged less than 17 years) with an encephalopathy due to a rapidly progressing underlying neurological disorder

• Subjects who have any of the following:

  1. a glomerular filtration rate (GFR) low enough to warrant dialysis but for whatever reason, dialysis is not planned or non-continuous dialysis planned (that would not adequately remove Captisol®);
  2. severe cardiogenic or vasodilatory shock requiring two or more pressors that is not related to third-line agent use;
  3. fulminant hepatic failure;
  4. no reasonable expectation of recovery (for instance, a likely outcome is persistent vegetative state) or life-expectancy, in the experience of the investigator, is less than 30 days.
• Subjects who are being administered more than three third-line agents concomitantly or in whom the qualifying wean cannot be completed per protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: SAGE-547; Intravenous	Drug: SAGE-547
PLACEBO_COMPARATOR: Placebo; Intravenous	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Able to be Weaned Off All Third-Line Agents Prior to End of Double-Blind SAGE-547 or Placebo Infusion, and Remain Off All Third-Line Agents for ≥ 24 Hours Following the End of SAGE-547 or Placebo Infusion	Third-line agents were anesthetic agents that were administered in order to reach a seizure or burst suppression electroencephalogram (EEG) pattern. For this study, third-line agents were defined as continuous intravenous infusions of pentobarbital/thiopental, midazolam, propofol, and ketamine at maintenance doses alone or in combination sufficient to produce a burst or seizure suppression pattern on the EEG. A responder was a participant who was able to be weaned off all third-line agents prior to the end of the SAGE-547 or placebo infusion and remain off all third-line agents for >=24 hours after the end of the study drug infusion. The primary analysis was a comparison between SAGE-547 and placebo of the proportion of responders.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time Between the Primary Outcome Response and the Re-institution of Any Third-line Agent for Seizure or Burst Suppression	Third-line agents were anesthetic agents that were administered in order to reach a seizure or burst suppression EEG pattern. For this study, third-line agents were defined as continuous intravenous infusions of pentobarbital/thiopental, midazolam, propofol, and ketamine at maintenance doses alone or in combination sufficient to produce a burst or seizure suppression pattern on the EEG. A responder was a participant who was able to be weaned off all third-line agents prior to the end of the SAGE-547 or placebo infusion and remain off all third-line agents for >=24 hours after the end of the study drug infusion. The primary analysis was a comparison between SAGE-547 and placebo of the proportion of responders.	Up to 21 days
Number of Participants Able to be Weaned Off All Third-line Agents Before the End of the First SAGE-547 or Placebo Infusion	Third-line agents were anesthetic agents that were administered in order to reach a seizure or burst suppression EEG pattern. For this study, third-line agents were defined as continuous intravenous infusions of pentobarbital/thiopental, midazolam, propofol, and ketamine at maintenance doses alone or in combination sufficient to produce a burst or seizure suppression pattern on the EEG.	Day 6
Time Between the Secondary Outcome Measure Response and the Re-institution of Any Third-line Agent for Seizure or Burst Suppression	Third-line agents were anesthetic agents that were administered in order to reach a seizure or burst suppression EEG pattern. For this study, third-line agents were defined as continuous intravenous infusions of pentobarbital/thiopental, midazolam, propofol, and ketamine at maintenance doses alone or in combination sufficient to produce a burst or seizure suppression pattern on the EEG.	Up to 21 days
Change in Clinical Global Impression Scale (CGI)	The CGI scale was used to integrate several sources of information into a single rating of a participant's condition. The CGI was rated on a 7-point scale, from a minimum of 0 to a maximum of 7, where 0 = Not assessed; 1 = Normal, not at all ill; 2 = Borderline physically ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill participants. A negative change from baseline indicates improvement. A positive change from baseline indicates worsening. Here, study visits followed by "R" indicate the Open-label Treatment Period.	Up to 21 days
Number of Days After the End of the First Study Drug Infusion Without Status Epilepticus, Up to Visit 12	Here, study visits followed by "R" indicate the Open-label Treatment Period.	Up to 21 days
Number of Days After the End of the First Study Drug Infusion Without Seizures (Convulsive and Non-convulsive), up to Visit 12	Here, study visits followed by "R" indicate the Open-label Treatment Period.	Up to 21 days
Number of Separate Episodes of Status Epilepticus Up to Visit 12	Here, study visits followed by "R" indicate the Open-label Treatment Period.	Up to 21 days
Number of Participants With a New Diagnosis of Epilepsy After Visit 11	Here, study visits followed by "R" indicate the Open-label Treatment Period.	Up to 21 days

Collaborators and Investigators

• Sponsor: Sage Therapeutics
• Investigators: Principal Investigator: Eric Rosenthal, MD, Massachusetts General Hospital; Principal Investigator: Mark Wainwright, MD, PhD, Ann & Robert H Lurie Children's Hospital of Chicago

Publications and helpful links

Helpful Links

• Sage Therapeutics

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (ACTUAL): July 18, 2017
• Study Completion (ACTUAL): August 11, 2017

Study Registration Dates

• First Submitted: June 2, 2015
• First Submitted That Met QC Criteria: June 22, 2015
• First Posted (ESTIMATE): June 23, 2015

Study Record Updates

• Last Update Posted (ACTUAL): January 28, 2022
• Last Update Submitted That Met QC Criteria: January 20, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Seizures; Status Epilepticus; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; GABA Modulators; GABA Agents; Neurosteroids; Brexanolone
• Other Study ID Numbers: 547-SSE-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.