Clinical trial NCT02477618: A Study With SAGE-547 for Super-Refractory Status Epilepticus
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Super-Refractory Status Epilepticus
Lead sponsor: Sage Therapeutics
Sponsor class: INDUSTRY
First posted: 2015-06-23
Enrollment: 132
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 7 days
Secondary outcomes:
measure: Time Between the Primary Outcome Response and the Re-institution of Any Third-line Agent for Seizure or Burst Suppression
timeFrame: Up to 21 days
measure: Number of Participants Able to be Weaned Off All Third-line Agents Before the End of the First SAGE-547 or Placebo Infusion
timeFrame: Day 6
measure: Time Between the Secondary Outcome Measure Response and the Re-institution of Any Third-line Agent for Seizure or Burst Suppression
timeFrame: Up to 21 days
measure: Change in Clinical Global Impression Scale (CGI)
timeFrame: Up to 21 days
measure: Number of Days After the End of the First Study Drug Infusion Without Status Epilepticus, Up to Visit 12
timeFrame: Up to 21 days
measure: Number of Days After the End of the First Study Drug Infusion Without Seizures (Convulsive and Non-convulsive), up to Visit 12
timeFrame: Up to 21 days
measure: Number of Separate Episodes of Status Epilepticus Up to Visit 12
timeFrame: Up to 21 days
measure: Number of Participants With a New Diagnosis of Epilepsy After Visit 11
timeFrame: Up to 21 days
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Sage Investigational Site
state: Alabama
city: Mobile
country: United States
facility: Sage Investigational Site
state: Alabama
city: Phoenix
country: United States
facility: Sage Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: Sage Investigational Site
state: Arizona
city: Little Rock
country: United States
facility: Sage Investigational Site
state: Arkansas
city: Fresno
country: United States
facility: Sage Investigational Site
state: California
city: Loma Linda
country: United States
facility: Sage Investigational Site
state: California
city: Los Angeles
country: United States
facility: Sage Investigational Site
state: California
city: Roseville
country: United States
facility: Sage Investigational Site
state: California
city: Sacramento
country: United States
facility: Sage Investigational Site
state: California
city: New Haven
country: United States
facility: Sage Investigational Site
state: Connecticut
city: Wilmington
country: United States
facility: Sage Investigational Site
state: Delaware
city: Washington
country: United States
facility: Sage Investigational Site
state: District of Columbia
city: Gainesville
country: United States
facility: Sage Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Sage Investigational Site
state: Florida
city: Miami
country: United States
facility: Sage Investigational Site
state: Florida
city: Orlando
country: United States
facility: Sage Investigational Site
state: Florida
city: Sarasota
country: United States
facility: Sage Investigational Site
state: Florida
city: Tampa
country: United States
facility: Sage Investigational Site
state: Florida
city: Weston
country: United States
facility: Sage Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Sage Investigational Site
state: Georgia
city: Atlanta
country: United States
facility: Sage Investigational Site
state: Georgia
city: Atlanta
country: United States
facility: Sage Investigational Site
state: Georgia
city: Honolulu
country: United States
facility: Sage Investigational Site
state: Hawaii
city: Honolulu
country: United States
facility: Sage Investigational Site
state: Hawaii
city: Boise
country: United States
facility: Sage Investigational Site
state: Idaho
city: Chicago
country: United States
facility: Sage Investigational Site
state: Illinois
city: Chicago
country: United States
facility: Sage Investigational Site
state: Illinois
city: Maywood
country: United States
facility: Sage Investigational Site
state: Illinois
city: Peoria
country: United States
facility: Sage Investigational Site
state: Illinois
city: Springfield
country: United States
facility: Sage Investigational Site
state: Illinois
city: Urbana
country: United States
facility: Sage Investigational Site
state: Illinois
city: Iowa City
country: United States
facility: Sage Investigational Site
state: Iowa
city: Wichita
country: United States
facility: Sage Investigational Site
state: Kansas
city: Lexington
country: United States
facility: Sage Investigational Site
state: Kentucky
city: Louisville
country: United States
facility: Sage Investigational Site
state: Kentucky
city: Baton Rouge
country: United States
facility: Sage Investigational Site
state: Louisiana
city: New Orleans
country: United States
facility: Sage Investigational Site
state: Louisiana
city: Portland
country: United States
facility: Sage Investigational Site
state: Maine
city: Baltimore
country: United States
facility: Sage Investigational Site
state: Maryland
city: Baltimore
country: United States
facility: Sage Investigational Site
state: Maryland
city: Boston
country: United States
facility: Sage Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: Sage Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: Sage Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: Sage Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: Sage Investigational Site
state: Massachusetts
city: Newton
country: United States
facility: Sage Investigational Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Sage Investigational Site
state: Michigan
city: Detroit
country: United States
facility: Sage Investigational Site
state: Michigan
city: Detroit
country: United States
facility: Sage Investigational Site
state: Michigan
city: East Lansing
country: United States
facility: Sage Investigational Site
state: Michigan
city: Grand Rapids
country: United States
facility: Sage Investigational Site
state: Michigan
city: Royal Oak
country: United States
facility: Sage Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: Sage Investigational Site
state: Minnesota
city: Rochester
country: United States
facility: Sage Investigational Site
state: Minnesota
city: Jackson
country: United States
facility: Sage Investigational Site
state: Mississippi
city: Kansas City
country: United States
facility: Sage Investigational Site
state: Missouri
city: Saint Louis
country: United States
facility: Sage Investigational Site
state: Missouri
city: Edison
country: United States
facility: Sage Investigational Site
state: New Jersey
city: Morristown
country: United States
facility: Sage Investigational Site
state: New Jersey
city: New Brunswick
country: United States
facility: Sage Investigational Site
state: New Jersey
city: Summit
country: United States
facility: Sage Investigational Site
state: New Jersey
city: Buffalo
country: United States
facility: Sage Investigational Site
state: New York
city: New York
country: United States
facility: Sage Investigational Site
state: New York
city: New York
country: United States
facility: Sage Investigational Site
state: New York
city: New York
country: United States
facility: Sage Investigational Site
state: New York
city: Port Jefferson
country: United States
facility: Sage Investigational Site
state: New York
city: Rochester
country: United States
facility: Sage Investigational Site
state: New York
city: Syracuse
country: United States
facility: Sage Investigational Site
state: New York
city: Durham
country: United States
facility: Sage Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Sage Investigational Site
state: North Carolina
city: Akron
country: United States
facility: Sage Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: Sage Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: Sage Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: Sage Investigational Site
state: Ohio
city: Columbus
country: United States
facility: Sage Investigational Site
state: Ohio
city: Toledo
country: United States
facility: Sage Investigational Site
state: Ohio
city: Portland
country: United States
facility: Sage Investigational Site
state: Oregon
city: Portland
country: United States
facility: Sage Investigational Site
state: Oregon
city: Portland
country: United States
facility: Sage Investigational Site
state: Oregon
city: Hershey
country: United States
facility: Sage Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Sage Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Sage Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Sage Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Sage Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Sage Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Sage Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: Sage Investigational Site
state: South Carolina
city: Memphis
country: United States
facility: Sage Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: Sage Investigational Site
state: Tennessee
city: Austin
country: United States
facility: Sage Investigational Site
state: Texas
city: Dallas
country: United States
facility: Sage Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Sage investigational Site
state: Texas
city: Salt Lake City
country: United States
facility: Sage Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: Sage Investigational Site
state: Utah
city: Burlington
country: United States
facility: Sage Investigational Site
state: Vermont
city: Seattle
country: United States
facility: Sage Investigational Site
state: Washington
city: Huntington
country: United States
facility: Sage Investigational Site
state: West Virginia
city: Morgantown
country: United States
facility: Sage Investigational Site
state: West Virginia
city: Wauwatosa
country: United States
facility: Sage Investigational Site
state: Wisconsin
city: Innsbruck
country: Austria
facility: Sage Investigational Site
city: Salzburg
country: Austria
facility: Sage Investigational Site
city: Vancouver
country: Canada
facility: Sage Investigational Site
state: British Columbia
city: Hamilton
country: Canada
facility: Sage Investigational Site
state: Ontario
city: Kingston
country: Canada
facility: Sage Investigational Site
state: Ontario
city: London
country: Canada
facility: Sage Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: Sage Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: Sage Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: Sage Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: Sage Investigational Site
state: Quebec
city: Montréal
country: Canada
facility: Sage Investigational Site
state: Quebec
city: Montréal
country: Canada
facility: Sage Investigational Site
state: Quebec
city: Copenhagen
country: Denmark
facility: Sage Investigational Site
city: Tallinn
country: Estonia
facility: Sage Investigational Site
city: Tallinn
country: Estonia
facility: Sage Investigational Site
city: Tartu
country: Estonia
facility: Sage Investigational Site
city: Helsinki
country: Finland
facility: Sage Investigational Site
city: Kuopio
country: Finland
facility: Sage Investigational Site
city: Bron Cedex
country: France
facility: Sage Investigational Site
city: Dijon
country: France
facility: Sage Investigational Site
city: Lille
country: France
facility: Sage Investigational Site
city: Limoges
country: France
facility: Sage Investigational Site
city: Lyon
country: France
facility: Sage Investigational Site
city: Paris
country: France
facility: Sage Investigational Site
city: Hamburg
country: Germany
facility: Sage Investigational Site
city: Marburg
country: Germany
facility: Sage Investigational Site
city: Osnabruck
country: Germany
facility: Sage Investigational Site
city: Balassagyarmat
country: Hungary
facility: Sage Investigational Site
city: Budapest
country: Hungary
facility: Sage Investigational Site
city: Budapest
country: Hungary
facility: Sage Investigational Site
city: Ashqelon
country: Israel
facility: Sage Investigational Site
city: Holon
country: Israel
facility: Sage Investigational Site
city: Holon
country: Israel
facility: Sage Investigational Site
city: Jerusalem
country: Israel
facility: Sage Investigational Site
city: Petach Tikva
country: Israel
facility: Sage Investigational Site
city: Tel Hashomer
country: Israel
facility: Sage Investigational Site
city: Tzrifin
country: Israel
facility: Sage Investigational Site
city: Bologna
country: Italy
facility: Sage Investigational Site
city: Firenze
country: Italy
facility: Sage Investigational Site
city: Florence
country: Italy
facility: Sage Investigational Site
city: Milano
country: Italy
facility: Sage Investigational Site
city: Milano
country: Italy
facility: Sage Investigational Site
city: Milan
country: Italy
facility: Sage Investigational Site
city: Modena
country: Italy
facility: Sage Investigational Site
city: Modena
country: Italy
facility: Sage Investigational Site
city: Monza
country: Italy
facility: Sage Investigational Site
city: Perugia
country: Italy
facility: Sage Investigational Site
city: Reggio Calabria
country: Italy
facility: Sage Investigational Site
city: Rome
country: Italy
facility: Sage Investigational Site
city: Rome
country: Italy
facility: Sage Investigational Site
city: Verona
country: Italy
facility: Sage Investigational Site
city: Enschede
country: Netherlands
facility: Sage Investigational Site
city: Heerlen
country: Netherlands
facility: Sage Investigational Site
city: Maastricht
country: Netherlands
facility: Sage Investigational Site
city: Nijmegen
country: Netherlands
facility: Sage Investigational Site
city: Belgrade
country: Serbia
facility: Sage Investigational Site
city: Belgrade
country: Serbia
facility: Sage Investigational Site
city: Nis
country: Serbia
facility: Sage Investigational Site
city: Novi Sad
country: Serbia
facility: Sage Investigational Site
city: Badalona
country: Spain
facility: Sage Investigational Site
city: Barakaldo
country: Spain
facility: Sage Investigational Site
city: Barcelona
country: Spain
facility: Sage Investigational Site
city: Barcelona
country: Spain
facility: Sage Investigational Site
city: Cordoba
country: Spain
facility: Sage Investigational Site
city: Granada
country: Spain
facility: Sage Investigational Site
city: Hospitalet de Llobregat
country: Spain
facility: Sage Investigational Site
city: Madrid
country: Spain
facility: Sage Investigational Site
city: Gothenburg
country: Sweden
facility: Sage Investigational Site
city: Manchester
country: United Kingdom
facility: Sage Investigational Site
city: Norfolk
country: United Kingdom
facility: Sage Investigational Site
city: Norwich
country: United Kingdom
facility: Sage Investigational Site
city: Staffordshire
country: United Kingdom
facility: Sage Investigational Site
city: Stoke-on-Trent
country: United Kingdom
facility: Sage Investigational Site
Study officials:
affiliation: Massachusetts General Hospital
name: Eric Rosenthal, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ann & Robert H Lurie Children's Hospital of Chicago
name: Mark Wainwright, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: