Study to Evaluate SAGE-547 Injection as Adjunctive Therapy for the Treatment of Super-Refractory Status Epilepticus (SRSE)

Supernus Pharmaceuticals

Status and phase: Completed; Phase 2; Phase 1

Conditions: Super-refractory Status Epilepticus

Treatments: Drug: SAGE-547

Study type: Interventional

Funder types: Industry

Identifiers

NCT02052739

547-SSE-201

Details and patient eligibility

About

The purpose of this study is to evaluate the safety and tolerability of SAGE-547 in participants in super-refractory status epilepticus (SRSE).

Full description

This is an open-label study consisting of a screening period (1 day), 4-day treatment period (96 hours) followed by a 1-day dose taper period (24 hours), a 2-day acute follow-up period, and a 3 week extended follow-up period.

On Day 1 of treatment SRSE participants under seizure suppression or burst-suppression with a continuous intravenous (IV) anti-epileptic drug (AED) (third-line agent) were given a 1-hour IV loading infusion of SAGE-547 followed by a maintenance infusion. After 48 hours of SAGE-547 treatment, the continuous IV AED (third-line agent) was weaned while continuing SAGE-547 at the maintenance infusion for the remainder of the treatment period. After 96 hours (4 days) of therapy with SAGE-547, the dose was to be tapered and discontinued over 24 hours.

The participants would have routine continuous electroencephalogram (EEG) monitoring during the screening period, and continuing until 48 hours after SAGE-547 treatment had completed. Participants would then have follow-up examinations weekly for the next 3 weeks (Days 8, 15, 22, and 29), during which safety and functional assessments would be obtained. Apart from treatment with SAGE-547, all participants would receive the standard of care for adults in SRSE along with ongoing treatment for all underlying medical conditions.

Enrollment: 25 patients

Sex: All

Ages: 2+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants 2 years of age and older.

• Participants with an EEG-confirmed SRSE diagnosis under concomitant therapy with a continuous IV AED (third-line agent) for ≥ 24 hours. For this study, SRSE is defined by the following criteria and in accordance with those used at major epilepsy treatment centers:

  • Failure 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
  • Failure 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
  • Presence of one or more breakthrough seizures > 6 hours after initiation of the continuous IV AED/third-line agent (e.g., pentobarbital, midazolam, propofol).

Exclusion criteria

• Participants with SRSE due to anoxic/hypoxic encephalopathy, children (participants aged less than 18 years) with an encephalopathy due to an underlying progressive neurological disorder.
• Participants with clinically significant electrocardiogram abnormalities.
• Participants with a significant medical or surgical condition that may compromise vital organ systems, or other conditions that would place the participants at increased risk such as dialysis or acute respiratory distress syndrome, severe cardiogenic or vasodilatory shock requiring 2 or more pressors, fulminant hepatic failure, etc.
• Participants who are receiving a continuous IV AED (third-line agent) for seizure suppression or burst-suppression that would require greater than 24 hours to wean.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

25 participants in 2 patient groups

SAGE-547 Standard Dose

Experimental group

Description:

Participants received SAGE-547 IV loading infusion of 286.6 micrograms per kilogram per hour (μg/kg/hr) for 1 hour on Day 1 followed by maintenance infusion of 86 μg/kg/hr for next 95 hours from Days 1 to 4 (i.e. up to Hour 96) followed by taper infusions of 64.5 μg/kg/hr, 43.0 μg/kg/hr, 21.5 μg/kg/hr at a duration of 8 hours each, on Day 5.

Treatment:

Drug: SAGE-547

SAGE-547 High Dose

Experimental group

Description:

Participants received SAGE-547 IV loading infusion of 286.6 μg/kg/hr for 1 hour on Day 1 followed by maintenance infusion A of SAGE-547 86 μg/kg/hr for 23 hours on Day 1 followed by maintenance infusion B of SAGE-547 156 μg/kg/hr for 72 hours from Days 2 to 4 followed by taper infusions of 125 μg/kg/hr, 94 μg/kg/hr, 62 μg/kg/hr, 31 μg/kg/hr at a duration of 6 hours each, on Day 5.

Treatment:

Drug: SAGE-547