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

Super-Refractory Status Epilepticus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02477618
• Other study ID #: 547-SSE-301
• Status: Completed
• Phase: Phase 3
• Start date: June 2015
• Est. completion date: August 11, 2017

Study information

• Verified date: January 2022
• Source: Sage Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 132
• Est. completion date: August 11, 2017
• Est. primary completion date: July 18, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Status Epilepticus
• Super-Refractory Status Epilepticus

Intervention

Drug:
• SAGE-547

• Placebo
Placebo

Locations

Country	Name	City	State
Austria	Sage Investigational Site	Innsbruck
Austria	Sage Investigational Site	Salzburg
Canada	Sage Investigational Site	Hamilton	Ontario
Canada	Sage Investigational Site	Kingston	Ontario
Canada	Sage Investigational Site	London	Ontario
Canada	Sage Investigational Site	Montreal	Quebec
Canada	Sage Investigational Site	Montreal	Quebec
Canada	Sage Investigational Site	Montreal	Quebec
Canada	Sage Investigational Site	Montreal	Quebec
Canada	Sage Investigational Site	Montréal	Quebec
Canada	Sage Investigational Site	Montréal	Quebec
Canada	Sage Investigational Site	Vancouver	British Columbia
Denmark	Sage Investigational Site	Copenhagen
Estonia	Sage Investigational Site	Tallinn
Estonia	Sage Investigational Site	Tallinn
Estonia	Sage Investigational Site	Tartu
Finland	Sage Investigational Site	Helsinki
Finland	Sage Investigational Site	Kuopio
France	Sage Investigational Site	Bron Cedex
France	Sage Investigational Site	Dijon
France	Sage Investigational Site	Lille
France	Sage Investigational Site	Limoges
France	Sage Investigational Site	Lyon
France	Sage Investigational Site	Paris
Germany	Sage Investigational Site	Hamburg
Germany	Sage Investigational Site	Marburg
Germany	Sage Investigational Site	Osnabruck
Hungary	Sage Investigational Site	Balassagyarmat
Hungary	Sage Investigational Site	Budapest
Hungary	Sage Investigational Site	Budapest
Israel	Sage Investigational Site	Ashqelon
Israel	Sage Investigational Site	Holon
Israel	Sage Investigational Site	Holon
Israel	Sage Investigational Site	Jerusalem
Israel	Sage Investigational Site	Petach Tikva
Israel	Sage Investigational Site	Tel Hashomer
Israel	Sage Investigational Site	Tzrifin
Italy	Sage Investigational Site	Bologna
Italy	Sage Investigational Site	Firenze
Italy	Sage Investigational Site	Florence
Italy	Sage Investigational Site	Milan
Italy	Sage Investigational Site	Milano
Italy	Sage Investigational Site	Milano
Italy	Sage Investigational Site	Modena
Italy	Sage Investigational Site	Modena
Italy	Sage Investigational Site	Monza
Italy	Sage Investigational Site	Perugia
Italy	Sage Investigational Site	Reggio Calabria
Italy	Sage Investigational Site	Rome
Italy	Sage Investigational Site	Rome
Italy	Sage Investigational Site	Verona
Netherlands	Sage Investigational Site	Enschede
Netherlands	Sage Investigational Site	Heerlen
Netherlands	Sage Investigational Site	Maastricht
Netherlands	Sage Investigational Site	Nijmegen
Serbia	Sage Investigational Site	Belgrade
Serbia	Sage Investigational Site	Belgrade
Serbia	Sage Investigational Site	Nis
Serbia	Sage Investigational Site	Novi Sad
Spain	Sage Investigational Site	Badalona
Spain	Sage Investigational Site	Barakaldo
Spain	Sage Investigational Site	Barcelona
Spain	Sage Investigational Site	Barcelona
Spain	Sage Investigational Site	Cordoba
Spain	Sage Investigational Site	Granada
Spain	Sage Investigational Site	Hospitalet de Llobregat
Spain	Sage Investigational Site	Madrid
Sweden	Sage Investigational Site	Gothenburg
United Kingdom	Sage Investigational Site	Manchester
United Kingdom	Sage Investigational Site	Norfolk
United Kingdom	Sage Investigational Site	Norwich
United Kingdom	Sage Investigational Site	Staffordshire
United Kingdom	Sage Investigational Site	Stoke-on-Trent
United States	Sage Investigational Site	Akron	Ohio
United States	Sage Investigational Site	Ann Arbor	Michigan
United States	Sage Investigational Site	Atlanta	Georgia
United States	Sage Investigational Site	Atlanta	Georgia
United States	Sage Investigational Site	Atlanta	Georgia
United States	Sage Investigational Site	Austin	Texas
United States	Sage Investigational Site	Baltimore	Maryland
United States	Sage Investigational Site	Baltimore	Maryland
United States	Sage Investigational Site	Baton Rouge	Louisiana
United States	Sage Investigational Site	Birmingham	Alabama
United States	Sage Investigational Site	Boise	Idaho
United States	Sage Investigational Site	Boston	Massachusetts
United States	Sage Investigational Site	Boston	Massachusetts
United States	Sage Investigational Site	Boston	Massachusetts
United States	Sage Investigational Site	Boston	Massachusetts
United States	Sage Investigational Site	Boston	Massachusetts
United States	Sage Investigational Site	Buffalo	New York
United States	Sage Investigational Site	Burlington	Vermont
United States	Sage Investigational Site	Charleston	South Carolina
United States	Sage Investigational Site	Chicago	Illinois
United States	Sage Investigational Site	Chicago	Illinois
United States	Sage Investigational Site	Cincinnati	Ohio
United States	Sage Investigational Site	Cincinnati	Ohio
United States	Sage Investigational Site	Cleveland	Ohio
United States	Sage Investigational Site	Columbus	Ohio
United States	Sage Investigational Site	Dallas	Texas
United States	Sage Investigational Site	Detroit	Michigan
United States	Sage Investigational Site	Detroit	Michigan
United States	Sage Investigational Site	Durham	North Carolina
United States	Sage Investigational Site	East Lansing	Michigan
United States	Sage Investigational Site	Edison	New Jersey
United States	Sage Investigational Site	Fresno	California
United States	Sage Investigational Site	Gainesville	Florida
United States	Sage Investigational Site	Grand Rapids	Michigan
United States	Sage Investigational Site	Hershey	Pennsylvania
United States	Sage Investigational Site	Honolulu	Hawaii
United States	Sage Investigational Site	Honolulu	Hawaii
United States	Sage Investigational Site	Huntington	West Virginia
United States	Sage Investigational Site	Iowa City	Iowa
United States	Sage Investigational Site	Jackson	Mississippi
United States	Sage Investigational Site	Jacksonville	Florida
United States	Sage Investigational Site	Kansas City	Missouri
United States	Sage Investigational Site	Lexington	Kentucky
United States	Sage Investigational Site	Little Rock	Arkansas
United States	Sage Investigational Site	Loma Linda	California
United States	Sage Investigational Site	Los Angeles	California
United States	Sage Investigational Site	Louisville	Kentucky
United States	Sage Investigational Site	Maywood	Illinois
United States	Sage Investigational Site	Memphis	Tennessee
United States	Sage Investigational Site	Miami	Florida
United States	Sage Investigational Site	Minneapolis	Minnesota
United States	Sage Investigational Site	Mobile	Alabama
United States	Sage Investigational Site	Morgantown	West Virginia
United States	Sage Investigational Site	Morristown	New Jersey
United States	Sage Investigational Site	Nashville	Tennessee
United States	Sage Investigational Site	New Brunswick	New Jersey
United States	Sage Investigational Site	New Haven	Connecticut
United States	Sage Investigational Site	New Orleans	Louisiana
United States	Sage Investigational Site	New York	New York
United States	Sage Investigational Site	New York	New York
United States	Sage Investigational Site	New York	New York
United States	Sage Investigational Site	Newton	Massachusetts
United States	Sage Investigational Site	Orlando	Florida
United States	Sage Investigational Site	Peoria	Illinois
United States	Sage Investigational Site	Philadelphia	Pennsylvania
United States	Sage Investigational Site	Philadelphia	Pennsylvania
United States	Sage Investigational Site	Philadelphia	Pennsylvania
United States	Sage Investigational Site	Philadelphia	Pennsylvania
United States	Sage Investigational Site	Philadelphia	Pennsylvania
United States	Sage Investigational Site	Phoenix	Arizona
United States	Sage Investigational Site	Phoenix	Arizona
United States	Sage Investigational Site	Pittsburgh	Pennsylvania
United States	Sage Investigational Site	Port Jefferson	New York
United States	Sage Investigational Site	Portland	Maine
United States	Sage Investigational Site	Portland	Oregon
United States	Sage Investigational Site	Portland	Oregon
United States	Sage Investigational Site	Portland	Oregon
United States	Sage Investigational Site	Rochester	Minnesota
United States	Sage Investigational Site	Rochester	New York
United States	Sage Investigational Site	Roseville	California
United States	Sage Investigational Site	Royal Oak	Michigan
United States	Sage Investigational Site	Sacramento	California
United States	Sage Investigational Site	Saint Louis	Missouri
United States	Sage Investigational Site	Salt Lake City	Utah
United States	Sage Investigational Site	Salt Lake City	Utah
United States	Sage investigational Site	San Antonio	Texas
United States	Sage Investigational Site	Sarasota	Florida
United States	Sage Investigational Site	Seattle	Washington
United States	Sage Investigational Site	Springfield	Illinois
United States	Sage Investigational Site	Summit	New Jersey
United States	Sage Investigational Site	Syracuse	New York
United States	Sage Investigational Site	Tampa	Florida
United States	Sage Investigational Site	Toledo	Ohio
United States	Sage Investigational Site	Urbana	Illinois
United States	Sage Investigational Site	Washington	District of Columbia
United States	Sage Investigational Site	Wauwatosa	Wisconsin
United States	Sage Investigational Site	Weston	Florida
United States	Sage Investigational Site	Wichita	Kansas
United States	Sage Investigational Site	Wilmington	Delaware
United States	Sage Investigational Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sage Therapeutics

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Denmark,  Estonia,  Finland,  France,  Germany,  Hungary,  Israel,  Italy,  Netherlands,  Serbia,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

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