SAGE 547-302

SAGE 547-302: To Evaluate Open-Label Use of SAGE-547 (Allopregnanolone) in the Treatment of Subjects with Super-Refractory Status Epilepticus

Supported by: SAGE

Principal Investigator at BMC: Anna Cervantes-Arslanian, MD

Inclusion Criteria:

Subjects who have:

1. Failed to respond to the administration of at least one first-line agent (eg, benzodiazepine or other emergent initial AED treatment), according to the institution’s standard of care, and;
2. Failed to respond to at least one second-line agent (eg, phenytoin, fosphenytoin, valproate, phenobarbital, levetiracetam, or other urgent control AEDs), according to the institution’s standard of care, and;
3. Not previously been administered a third-line agent, but have been admitted to an ICU 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 agents 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 at least one continuous infusion of a third-line agent or are on one or more continuous infusions of third-line agents, but not in an EEG burst suppression pattern.

Exclusion Criteria: 

1. Subjects who are pregnant;
2. Subjects with a known allergy to progesterone or allopregnanolone or any excipients in SAGE-547;
3. Subjects with SRSE due to anoxic/hypoxic encephalopathy;
4. Subjects who have any of the following:
   a.    GFR low enough to warrant dialysis but for whatever reason, dialysis that would adequately remove Captisol is not planned;
   b.    Severe cardiogenic or vasodilatory shock requiring 2 or more pressors that is not related to third-line agent use;
   c.    Fulminant hepatic failure;
   d.    No reasonable expectation of recovery (for instance, a likely outcome is persistent vegetative state) or life-expectancy, in the opinion of the investigator, of less than 30 days;
   e.    Do not resuscitate (DNR) order;
5. Subjects who are being administered more than 3 third-line agents concomitantly or in whom the qualifying wean cannot be completed within 24 hours; or who are being administered a third-line agent for other indications such as raised intra-cranial pressure that would preclude weaning according to this protocol;
6. Subjects with a living will that does not allow heroic measures;
7. 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 Study 547-SSE-302 is allowed;
8. Subjects who have been treated with study drug or randomized in this or any other trial employing SAGE-547 previously;
9. Subjects for whom it is not medically feasible to be transferred to a geographically accessible participating clinical trial site for Study 547-SSE-301.