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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2015 by Sage Therapeutics
Sponsor:
Information provided by (Responsible Party):
Sage Therapeutics
ClinicalTrials.gov Identifier:
NCT02052739
First received: January 28, 2014
Last updated: April 9, 2015
Last verified: April 2015
  Purpose

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


Condition Intervention Phase
Super-refractory Status Epilepticus
Drug: SAGE-547
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of SAGE-547 Injection as Adjunctive Therapy for the Treatment of Super-Refractory Status Epilepticus

Resource links provided by NLM:


Further study details as provided by Sage Therapeutics:

Primary Outcome Measures:
  • Safety and tolerability in subjects in super-refractory status epilepticus (SRSE) [ Time Frame: 29 Days ] [ Designated as safety issue: Yes ]
    Safety will be evaluated via clinical laboratory measures, vitals, EEG and ECG throughout the 29 day study period


Secondary Outcome Measures:
  • Efficacy of SAGE-547 on super-refractory status epilepticus as indicated by the need to re-institute a continuous IV AED (third-line agent), for refractory seizure control as well as the duration of the observed response [ Time Frame: 96 hours ] [ Designated as safety issue: No ]
  • Pharmacokinetics (PK) of SAGE-547 exposure [ Time Frame: 7 Days ] [ Designated as safety issue: No ]
    Plasma PK parameters will be calculated where appropriate (eg, Cmax, Cmin, Tmax, AUClast, AUC∞, CLs). It will be collected prior to, during, and after completion of SAGE-547 dosing.


Estimated Enrollment: 40
Study Start Date: January 2014
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: active drug
SAGE-547
Drug: SAGE-547
Intravenous

Detailed 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 subjects under seizure suppression or burst-suppression with a continuous IV AED (third-line agent) will be 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) will be 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 will be tapered and discontinued over 24 hours.

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

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects 2 years of age and older.
  • Subjects 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:

  • Subjects with SRSE due to anoxic/hypoxic encephalopathy, children (subjects aged less than 18 years) with an encephalopathy due to an underlying progressive neurological disorder.
  • Subjects with clinically significant electrocardiogram (ECG) abnormalities.
  • Subjects with a significant medical or surgical condition that may compromise vital organ systems, or other conditions that would place the subject 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.
  • Subjects who are receiving a continuous IV AED (third-line agent) for seizure suppression or burst-suppression that will require greater than 24 hours to wean.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02052739

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Nancy Cohen    205-934-7244    ncohen@uab.edu   
Principal Investigator: Jerzy P. Szaflarski, MD, PhD         
United States, Florida
Intercoastal Medical Group Recruiting
Sarasota, Florida, United States, 34239
Contact: Jeanette Wilson, RN    941-330-1864      
Principal Investigator: Leonie van Passel, MD         
United States, Illinois
Ann and Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Allison Rusie       arusie@luriechildrens.org   
Principal Investigator: Mark Wainwright, MD, PhD         
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Irena I Garić, RN, MPH    312-926-1672    igaric@nmff.org   
Principal Investigator: Elizabeth Gerard, MD         
United States, Kansas
Via Christi Epilepsy Center Recruiting
Wichita, Kansas, United States, 67214
Contact: Tony Sadler, PA-C    316-268-5932    toni.sadler@via-christi.org   
Principal Investigator: Aamr Herekar, MD         
United States, Louisiana
Ochsner Clinic Foundation Recruiting
New Orleans, Louisiana, United States, 70121
Contact: WIlliam Nganongo    504-842-5098      
Principal Investigator: Eugene Ramsay, MD         
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Li Qing Chen    617-525-7638      
Principal Investigator: Henrikas Vaitkevicius, MD         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Abigail Cohen    617-724-2829    acohen18@partners.org   
Principal Investigator: Eric Rosenthal, MD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Jamie Miller    734-936-4817      
Principal Investigator: Daniela Minecan, MD         
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48322
Contact: Lauren Tack    313-916-3528    LTACK1@hfhs.org   
Principal Investigator: Panayiotis Varelas, MD         
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Cristina Falo, PhD    212-305-6071      
Principal Investigator: Jan Claassen, MD, PhD         
University of Rochester Recruiting
Rochester, New York, United States, 14642
Contact: Noreen Connolly    585-275-0589    Noreen_Connolly@URMC.Rochester.edu   
Principal Investigator: Olga Selioutski, MD         
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Brian Mace    919-684-0081    brian.mace@duke.edu   
Principal Investigator: Keith Dombrowski, MD         
Wake Forest Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Sara Vaughan       svaughan@wakehealth.edu   
Principal Investigator: Cormac O'Donovan, MD         
United States, Pennsylvania
The University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Kelsey Nawalinski       Neurosurgery-NCRD@uphs.upenn.edu   
Principal Investigator: Joshua Levine, MD         
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Melissa R. Osborn, RN, BSN, CCRP       melissa.osborn@Vanderbilt.Edu   
Principal Investigator: Kevin Haas, MD, PhD         
United States, Texas
Neurological Clinic of Texas, PA Recruiting
Dallas, Texas, United States, 75251
Contact: Sara Gonzales    972-707-8378      
Principal Investigator: Neurology and Neurophysiology         
Baylor Scott & White Recruiting
Temple, Texas, United States, 76504
Contact: Richard Castillo, CCRP    254-724-7727      
Principal Investigator: Batool F. Kirmani, MD         
Sponsors and Collaborators
Sage Therapeutics
Investigators
Study Chair: Stephen J Kanes, M.D., Ph.D. Sage Therapeutics
  More Information

Additional Information:
No publications provided

Responsible Party: Sage Therapeutics
ClinicalTrials.gov Identifier: NCT02052739     History of Changes
Other Study ID Numbers: 547-SSE-201
Study First Received: January 28, 2014
Last Updated: April 9, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Sage Therapeutics:
Status Epilepticus
Refractory status epilepticus
Super-refractory status epilepticus
SAGE-547
SAGE
Sage Therapeutics

Additional relevant MeSH terms:
Status Epilepticus
Brain Diseases
Central Nervous System Diseases
Epilepsy
Nervous System Diseases

ClinicalTrials.gov processed this record on May 25, 2015