547-SSE-201 for Super-Refractory Status Epilepticus: Response and Relationship to Underlying Patient Characteristics (S14.003)

Objectives: The objectives of the phase 1/2 study were to evaluate the safety and tolerability of SAGE-547 in super-refractory status epilepticus (SRSE) patients. Secondary objectives were to assess the efficacy and pharmacokinetics (PK) of SAGE-547, and to assess overall outcomes at 1 month posttreatment. Background: SAGE-547 is a solution of allopregnanolone in Captisol®. There is evidence indicating a role for allopregnanolone in the treatment of seizures and status epilepticus (SE) supporting the hypothesis that SAGE-547 may provide anticonvulsant efficacy at a time when prolonged seizure activity has become resistant to benzodiazepines. Design/Methods: Under an open-label, single-arm study design, patients ≥2 years diagnosed with SRSE underwent 5 days of SAGE-547 treatment. Outcome measures were: 1) successful wean off of continuous intravenous antiseizure medications (cIV-AED) after hour 48; 2) successful taper off SAGE-547 after hour 96. Additional measures included Clinical Global Impression of Severity/Improvement, GCS, and cEEG. Results: The 547-SSE-201 trial recruited 25 patients who all received open-label therapy with SAGE-547. 77[percnt] (19/22) of evaluable patients were successfully weaned off both the anesthetic agent(s) used to suppress status epilepticus as well as SAGE-547. Responses were not related to underlying medical condition, type or number of cIV-AED administered, underlying AED treatment, age, gender, or ethnicity. 65[percnt] of patients experienced at least 1 serious adverse event (SAE) and 6 patients died during the trial; neither the SAEs nor the deaths were attributed to SAGE-547 administration. Conclusion: In a critically ill population at high baseline risk, this phase 1/2 clinical trial supports further investigation of SAGE-547 in SRSE based on outcomes as measured by successful weaning of anesthetic infusions and study drug in previously refractory patients. Subsequent evidence for SAGE-547 clinical efficacy and safety in the treatment of SRSE will be determined by an ongoing phase 3, randomized, placebo-controlled trial. Study supported by: SAGE Therapeutics. Disclosure: Dr. Kanes has received personal compensation for activities with Sage Therapeutics. Dr. Rosenthal has received research support from Sage Therapeutics. Dr. Vaitkevicius has nothing to disclose. Dr. Claassen has received personal compensation for activities with the JSMF Foundation, Actelion, and SAGE Pharmaceutical. Dr. Wainwright has received personal compensation for activities with Sage Therapeutics. Dr. Hoffman has received personal compensation for activities with Sage Therapeutics. Dr. Baird received personal compensation for activities with Sage Therapeutics. Dr. Quirk has received personal compensation for activities with Sage Therapeutics. Dr. Colquhoun has received personal compensation for activities with Sage Therapeutics.