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

Phase 3

Completed

• Conditions: Super-Refractory Status Epilepticus
• Interventions: Drug: Placebo; Drug: SAGE-547

• Registration Number: NCT02477618
• Lead Sponsor: Sage Therapeutics

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2015-06
• Study First Submitted: 2015-06-02
• Study First Submitted QC: 2015-06-22
• Study First Posted: 2015-06-23
• Primary Completion: 2017-07-18
• Study Completion: 2017-08-11
• Disposition First Submitted: 2018-07-18
• Disposition First Submitted QC: 2018-07-18
• Disposition First Posted: 2018-07-20
• Results First Submitted: 2019-04-11
• Results First Submitted QC: 2019-04-11
• Results First Posted: 2019-05-02
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-20
• Last Update Posted: 2022-01-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 132

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Intravenous
SAGE-547	SAGE-547	Intravenous

Primary Outcome Measures

Name	Time	Method
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	7 days	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.

Secondary Outcome Measures

Name	Time	Method
Time Between the Primary Outcome Response and the Re-institution of Any Third-line Agent for Seizure or Burst Suppression	Up to 21 days	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.
Number of Participants With a New Diagnosis of Epilepsy After Visit 11	Up to 21 days	Here, study visits followed by "R" indicate the Open-label Treatment Period.
Time Between the Secondary Outcome Measure Response and the Re-institution of Any Third-line Agent for Seizure or Burst Suppression	Up to 21 days	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.
Number of Separate Episodes of Status Epilepticus Up to Visit 12	Up to 21 days	Here, study visits followed by "R" indicate the Open-label Treatment Period.
Number of Participants Able to be Weaned Off All Third-line Agents Before the End of the First SAGE-547 or Placebo Infusion	Day 6	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.
Number of Days After the End of the First Study Drug Infusion Without Status Epilepticus, Up to Visit 12	Up to 21 days	Here, study visits followed by "R" indicate the Open-label Treatment Period.
Change in Clinical Global Impression Scale (CGI)	Up to 21 days	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.
Number of Days After the End of the First Study Drug Infusion Without Seizures (Convulsive and Non-convulsive), up to Visit 12	Up to 21 days	Here, study visits followed by "R" indicate the Open-label Treatment Period.

Trial Locations

Locations (2)

Sage Investigational Site; 🇬🇧 Stoke-on-Trent, United Kingdom

Sage investigational Site; 🇺🇸 San Antonio, Texas, United States