SUPER-REFRACTORY STATUS EPILEPTICUS (SRSE) MedDRA version: 18.0 Level: PT Classification code 10041962 Term: Status epilepticus System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Code: SAGE-547
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: not available yet
CAS Number: 516-54-1
Current Sponsor code: SAGE-547
Other descriptive name: allopregn
Sponsors
Sage Therapeutics
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects two (2) years of age and older. 2. Subjects who have: • Failed to respond to the administration of at least one first-line agent (e.g., benzodiazepine or other emergent initial 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 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 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 suppression pattern Are the trial subjects under 18? yes Number of subjects for this age range: 28 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 84 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 28
Exclusion criteria
Exclusion criteria: 1. Subjects who are pregnant. 2. Subjects with a known allergy to progesterone or allopregnanolone. 3. Subjects with SRSE due to anoxic/hypoxic encephalopathy. 4. Children (subjects aged less than 17 years) with an encephalopathy due to a rapidly progressing underlying neurological disorder. 5. Subjects who have any of the following: -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®); -severe cardiogenic or vasodilatory shock requiring two or more pressors that is not related to third-line agent use; -fulminant hepatic failure; -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; -a do not resuscitate (DNR) order. 6. Subjects who are being administered more than three third-line agents concomitantly or for whom the qualifying wean cannot be completed within 24 hours or who are being administered a third-line agent for indications such as raised intra-cranial pressure that would preclude weaning according to this protocol. 7. Subjects with a living will that does not allow heroic measure. 8. Subjects who have been exposed to an investigational medication or device within 30 days; the exception to this is that participation in the Established Status Epilepticus Treatment Trial or ESETT within 30 days of screening for the 547-SSE-301 trial is allowed. 9. Subjects who have been enrolled in this trial or any other trial employing SAGE-547 previously (i.e., subjects may not withdraw or complete and then re-enroll).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the response to a 144-hour (6 day) continuous intravenous infusion of SAGE-547 compared to placebo administered to support the weaning of all third-line agents in adult and pediatric subjects with SRSE, and for the response to endure at least 24 hours after cessation of the SAGE-547 or placebo infusion (primary response).;Secondary Objective: To compare between SAGE-547 and placebo: time between meeting primary response endpoint and re-institution of any third-line agent for seizure or burst suppression up to V12; secondary response, (success of weaning the subject off all third-line agents before end of the first infusion; time between meeting the secondary response endpoint and re-institution of any third-line agent for seizure or burst suppression up to V12; Change in the Clinical Global Impression scale up to V12; number of days after the end of the first infusion of study drug that the subject does not have status epilepticus, up to V12; number of days after end of the first infusion of study drug that the subject does not have seizures (convulsive and non-convulsive) up to V12; number of separate episodes of status epilepticus occurring up to V12; the proportion of subjects with a new diagnosis of epilepsy after V11. To determine safety and tolerability of a 144-hour infusion of SAGE-547.;Primary end point(s): Success or failure, with success defined as weaning the subject off all third-line agents before completion of the first blinded infusion of SAGE-547 or placebo, and not having to re-institute any third-line agent for seizure or burst suppression during the 24 hours after the end of the first infusion of SAGE-547 or placebo, and concurrent signs of physiologic brain activity as determined by EEG (primary response). ;Timepoint(s) of evaluation of this end point: 24 hours after the end of study drug infusion. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. The time between meeting the primary response endpoint and the re-institution of any third-line agent for seizure or burst suppression up to Visit 12; 2. Secondary response, defined as success of weaning the subject off all third-line agents before the end of the first SAGE-547 or placebo infusion; 3. The time between meeting the secondary response endpoint, defined in (2) above, and the re-institution of any third-line agent for seizure or burst suppression up to Visit 12; 4. The assessment of clinical status as measured by change in the CGI from Visit 1 (Screening) and to Visit 12; 5. The number of days after the end of the first study drug infusion that the subject does not have status epilepticus, up to Visit 12; 6. The number of days after the end of the first study drug infusion that the subject does not have seizures (convulsive and non-convulsive) up to Visit 12; 7. The number of separate episodes of status epilepticus occurring up to Visit 12; 8. The proportion of subjects with a new diagnosis of epilepsy after Visit 11. Safety endpoints: 1.Adverse events and medications; 2.Laboratory testing (hematology, serum chemistry, and urinalysis); 3.Vital signs (blood pressure, heart rate, temperature, and weight); 4.ECG parameters; 5.Mortality. ;Timepoint(s) of evaluation of this end point: Efficacy: up to visit 12 or after visit 11 for end-point # 8. Safety: AEs and medications: V1-V12 ECG and vital signs: V1, V3-V10 Lab tests: V1, V3, V4, V6, V8, V10,V11 Mortality: V12 Retreatment period: AE and medications: V3R-V12R ECG and vital signs: V3R-V10R Lab tests: V3R, V4R, V6R, V8R, V10R, V11R Mortality: V12R | — |
Countries
Austria, Belgium, Canada, Denmark, Finland, France, Germany, Hungary, Netherlands, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactMedical Director
SAGE Therapeutics
Outcome results
None listed