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

NCT ID: NCT02052739

Last Updated: 2025-09-15

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-03-21

Study Completion Date

2015-05-03

Brief Summary

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

Detailed Description

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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.

Conditions

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Super-refractory Status Epilepticus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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SAGE-547 Standard Dose

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.

Group Type EXPERIMENTAL

SAGE-547

Intervention Type DRUG

Solution for injection for IV infusion

SAGE-547 High Dose

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.

Group Type EXPERIMENTAL

SAGE-547

Intervention Type DRUG

Solution for injection for IV infusion

Interventions

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SAGE-547

Solution for injection for IV infusion

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

2 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Supernus Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Robert Lasser, MD, MBA

Role: STUDY_CHAIR

Sage Therapeutics

Locations

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Sage Investigational Site

Birmingham, Alabama, United States

Site Status

Sage Investigational Site

Sarasota, Florida, United States

Site Status

Sage Investigational Site

Chicago, Illinois, United States

Site Status

Sage Investigational Site

Wichita, Kansas, United States

Site Status

Sage Investigational Site

New Orleans, Louisiana, United States

Site Status

Sage Investigational Site

Boston, Massachusetts, United States

Site Status

Sage Investigational Site

Boston, Massachusetts, United States

Site Status

Sage Investigational Site

Ann Arbor, Michigan, United States

Site Status

Sage Investigational Site

Detroit, Michigan, United States

Site Status

Sage Investigational Site

New York, New York, United States

Site Status

Sage Investigational Site

Rochester, New York, United States

Site Status

Sage Investigational Site

Durham, North Carolina, United States

Site Status

Sage Investigational Site

Winston-Salem, North Carolina, United States

Site Status

Sage Investigational Site

Philadelphia, Pennsylvania, United States

Site Status

Sage Investigational Site

Nashville, Tennessee, United States

Site Status

Sage Investigational Site

Dallas, Texas, United States

Site Status

Sage Investigational Site

Temple, Texas, United States

Site Status

Countries

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United States

References

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Rosenthal ES, Claassen J, Wainwright MS, Husain AM, Vaitkevicius H, Raines S, Hoffmann E, Colquhoun H, Doherty JJ, Kanes SJ. Brexanolone as adjunctive therapy in super-refractory status epilepticus. Ann Neurol. 2017 Sep;82(3):342-352. doi: 10.1002/ana.25008. Epub 2017 Sep 11.

Reference Type BACKGROUND
PMID: 28779545 (View on PubMed)

Related Links

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http://www.sagerx.com/

Sage Therapeutics

Other Identifiers

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547-SSE-201

Identifier Type: -

Identifier Source: org_study_id

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