Randomized Therapy In Status Epilepticus (RAISE)

A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy and Safety of Intravenous Ganaxolone in Status Epilepticus

This study evaluated the effectiveness and safety of an investigational product (IP), intravenous (IV) ganaxolone, to treat participants with status epilepticus (SE).

Study Overview

• Status: Completed
• Conditions: Status Epilepticus
• Intervention / Treatment: Drug: Placebo; Drug: Ganaxolone

Detailed Description

This is a double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of IV ganaxolone in status epilepticus. Investigational product was added to standard of care following failure of any two or more antiseizure medications (benzodiazepine and one IV antiepileptic drug (AED) or two IV AEDs. Participants were screened for inclusion/exclusion criteria prior to receiving investigational product by continuous IV infusion. Participants were followed for approximately 4 weeks. Participants who are known to be at risk for SE were consented or assented prior to an SE event.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Marinus Research Site
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Marinus Research Site
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Marinus Research Site
    • Melbourne, Victoria, Australia, 3004
      • Marinus Research Site
    • Melbourne, Victoria, Australia, 3050
      • Marinus Research Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Marinus Research Site
    • Calgary, Alberta, Canada, T3B 6A8
      • Marinus Research Site
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Marinus Research Site
  • Quebec
    • Quebec City, Quebec, Canada, G1V 4G2
      • Marinus Research Site
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Marinus Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Marinus Research Site
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Marinus Research Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Marinus Research Site
  • California
    • Downey, California, United States, 90242
      • Marinus Research Site
    • La Jolla, California, United States, 92037
      • Marinus Research Site
    • Orange, California, United States, 92868
      • Marinus Research Site
    • Sacramento, California, United States, 95817
      • Marinus Research Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Marinus Research Site
    • Denver, Colorado, United States, 80204
      • Marinus Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Marinus Research Site
  • Florida
    • Gainesville, Florida, United States, 32608
      • Marinus Research Site
    • Miami, Florida, United States, 33136
      • Marinus Research Site #1
    • Miami, Florida, United States, 33136
      • Marinus Research Site
    • Miami, Florida, United States, 33155
      • Marinus Research Site
    • Port Saint Lucie, Florida, United States, 34987
      • Marinus Research Site
    • Tampa, Florida, United States, 33606
      • Marinus Research Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Marinus Research Site
    • Chicago, Illinois, United States, 60612
      • Marinus Research Site
    • Urbana, Illinois, United States, 61801
      • Marinus Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Marinus Research Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Marinus Research Site
    • Shreveport, Louisiana, United States, 71103
      • Marinus Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Marinus Research Site #1
    • Baltimore, Maryland, United States, 21201
      • Marinus Research Site
    • Baltimore, Maryland, United States, 21215
      • Marinus Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Marinus Research Site
    • Boston, Massachusetts, United States, 02111
      • Marinus Research Site
    • Boston, Massachusetts, United States, 02114
      • Marinus Research Site
    • Boston, Massachusetts, United States, 02118
      • Marinus Research Site
    • Boston, Massachusetts, United States, 02215
      • Marinus Research Site
    • Worcester, Massachusetts, United States, 01655
      • Marinus Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Marinus Research Site
    • Grand Rapids, Michigan, United States, 49503
      • Marinus Research Site
  • Missouri
    • Columbia, Missouri, United States, 65212
      • Marinus Research Site
    • Saint Louis, Missouri, United States, 63110
      • Marinus Research Site
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Marinus Research Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Marinus Research Site
  • New York
    • Albany, New York, United States, 12208
      • Marinus Research Site
    • Brooklyn, New York, United States, 11203
      • Marinus Research Site
    • New York, New York, United States, 10032
      • Marinus Research Site
    • New York, New York, United States, 10029
      • Marinus Research Site
    • Rochester, New York, United States, 14642
      • Marinus Research Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Marinus Research Site
    • Charlotte, North Carolina, United States, 28203
      • Marinus Research Site
    • Durham, North Carolina, United States, 27710
      • Marinus Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Marinus Research Site
    • Cleveland, Ohio, United States, 44195
      • Marinus Research Site
    • Columbus, Ohio, United States, 43210
      • Marinus Research Site
  • Oregon
    • Portland, Oregon, United States, 97225
      • Marinus Research Site
    • Portland, Oregon, United States, 97239
      • Marinus Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Marinus Research Site #1
    • Philadelphia, Pennsylvania, United States, 19104
      • Marinus Research Site #2
    • Philadelphia, Pennsylvania, United States, 19104
      • Marinus Research Site
    • Philadelphia, Pennsylvania, United States, 19107
      • Marinus Research Site
    • Philadelphia, Pennsylvania, United States, 19140
      • Marinus Research Site
    • Pittsburgh, Pennsylvania, United States, 15212
      • Marinus Research Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Marinus Research Site
    • Memphis, Tennessee, United States, 38103
      • Marinus Research Site
  • Texas
    • Dallas, Texas, United States, 75235
      • Marinus Research Site
    • Fort Worth, Texas, United States, 76104
      • Marinus Research Site
    • San Antonio, Texas, United States, 78229
      • Marinus Research Site
  • Utah
    • Murray, Utah, United States, 84107
      • Marinus Research Site
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Marinus Research Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Marinus Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participant, participant's parent, guardian, or legal authorized representative (LAR) must provide signed of informed consent/assent, and once capable (per institution guidelines), there must be documentation of consent/assent by the participant demonstrating they are willing and aware of the investigational nature of the study and related procedures. Where allowed by law, where the participant lacks the capacity to make informed decisions regarding his/her medical treatment options, the treating clinician may follow their deferred consenting practices. The clinician will make the final decision based on the best interests of the particiapant.
2. Male or females 12 years of age and older at the time of the first dose of IP

3. SE meeting the following criteria:

   a. A diagnosis of SE with or without prominent motor features based on clinical and EEG findings:

   i. Diagnosis is established by:

   • For SE with prominent motor features: Clinical and EEG seizure activity indicative of convulsive, myoclonic or focal motor SE.
   • For SE without prominent motor features (nonconvulsive SE): Appropriate clinical features and an EEG indicative of non-convulsive status epilepticus (NCSE)

   ii. For any type of SE:

   • At least 6 minutes of cumulative seizure activity over a 30-minute period within the hour before IP initiation, AND

   • Seizure activity during the 30 minutes immediately prior to IP initiation

     b. The treating clinician(s) anticipate that IV anesthesia is likely to be the next treatment for SE that persists following initiation of IP

4. Participants must have received any two or more of the following agents for treatment of the current episode of SE administered at an adequate dose and for a sufficient duration, in the judgment of the investigator, to demonstrate efficacy

   • Benzodiazepines,
   • IV Fosphenytoin/phenytoin,
   • IV Valproic acid,
   • IV Levetiracetam,
   • IV Lacosamide,
   • IV Brivaracetam, or
   • IV Phenobarbital
5. Body mass index (BMI) < 40 or, if BMI is not able to be calculated at screening, participant is assessed by investigator as not morbidly obese

Exclusion Criteria:

1. Life expectancy of less than 24 hours
2. Anoxic brain injury or an uncorrected rapidly reversable metabolic condition as the primary cause of SE (e.g., hypoglycemia < 50 milligram per deciliter [mg/dL] or hyperglycemia > 400 mg/dL)
3. Participants who have received high-dose IV anesthetics (e.g., midazolam, propofol, thiopental, or pentobarbital) during the current episode of SE for more than 18 hours, or who continue to have clinical or electrographic evidence of persistent seizures while receiving high-dose IV anesthetics.
4. Clinical condition or advance directive that would NOT permit use of IV anesthesia
5. Participants known or suspected to be pregnant
6. Participants with known allergy or sensitivity to progesterone or allopregnanolone medications/supplements
7. Receiving a concomitant IV product containing Captisol®
8. Known or suspected hepatic insufficiency or hepatic failure leading to impaired synthetic liver function.
9. Known or suspected stage 3B (moderate to severe; estimated glomerular filtration rate [eGFR] 44-30 milliliter/minutes/1.73-meter square [mL/min/1.73m^2]), stage 4 (severe; eGFR 29-15 mL/min/1.73m^2), or stage 5 (kidney failure; eGFR < 15 mL/min/1.73m^2 or dialysis) kidney disease
10. Use of an investigational product for which less than 30 days or 5 half-lives have elapsed from the final product administration. Participation in a non-interventional clinical study does not exclude eligibility.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: IV Placebo; Placebo bolus dose followed by continuous infusion for 36 hours, followed by 12 hour taper	Drug: Placebo; Placebo will be administered.
Experimental: IV ganaxolone active; Ganaxolone bolus dose followed by continuous infusion for 36 hours, followed by 12 hour taper	Drug: Ganaxolone; Ganaxolone will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With SE Cessation Within 30 Minutes of Investigational Product (IP) Initiation Without Medications for the Acute Treatment of SE	SE cessation was determined by the investigator based on clinical and electroencephalography (EEG). Medications for the acute treatment of SE were defined as antiepileptic drugs (AEDs) administered to abort ongoing SE or prevent imminent recurrence of SE based on clinical or EEG evidence.	Up to 30 minutes
Percentage of Participants With no Progression to Intravenous (IV) Anesthesia for 36 Hours Following Investigational Product (IP) Initiation	Percentage of participants with no progression to IV anesthesia for 36 hours following IP initiation SE cessation was based on investigator report with confirmation by assessment of concomitant medication data.	Up to 36 hours after IP initiation
Number of Participants With Treatment Emergent Adverse Events	An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant who has been administered a pharmaceutical product; it does not necessarily have a causal relationship with this treatment. Treatment-emergent adverse event (TEAE) is defined as an AE that occurred or worsened at the time of or following IP initiation.	Up to 4 weeks after IP initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With no Progression to IV Anesthesia for 72 Hours Following IP Initiation	Percentage of participants with no progression to IV anesthesia for 72 hours following IP initiation SE cessation was assessed by the investigator based on clinical and EEG features.	Up to 72 hours after IP initiation
Time to SE Cessation Following IP Initiation	Time to SE cessation was assessed for the first 72 hours following IP using the Kaplan-Meier method.	Up to 72 hours after IP initiation
Percentage of Participants With Any Escalation of Treatment in the First 24 Hours Following IP Initiation	SE cessation will be determined by the investigator based on clinical and EEG. Percentage of participants with any escalation of treatment in the first 24 hours following IP initiation, i.e. any medication other than IP administered for the acute treatment of SE in the first 24 hours following IP initiation was summarized	Up to 24 hours after IP initiation
Time to Treatment Escalation in the First 24 Hours Following IP Initiation	For time to treatment escalation (any mediation used for acute treatment of SE), the estimates are based descriptive statistics on participants with treatment escalation in the first 24 hours following IP initiation. For participants without treatment escalation, the time to treatment escalation was censored at IP completion, or discontinuation from the study or death, whichever occurs earlier. The median time to treatment escalation has been presented.	Up to 24 hours after IP initiation
Time to Initiation of Anesthesia for SE Treatment Through the Final Study Follow-up Visit/Contact	Time to initiation of anesthesia for SE treatment through the final study follow-up visit/contact, were calculated based on descriptive statistics. The estimate was censored at study discontinuation, death, or last follow-up of the participant, whichever occurs first. The median time to initiation of anesthesia has been presented.	Up to 4 Weeks following IP initiation
Percentage of Participants Who Develop Super Refractory Status Epilepticus (SRSE) Through the Final Study Follow-up Visit/Contact	Percentage of participants who developed SRSE through the final study follow-up visit/contact was provided for each treatment group.	Up to 4 Weeks following IP initiation
Percent Change From Baseline in Seizure Burden Through 72 Hours Following IP Initiation	The seizure burden through 72 hours following IP initiation is described as the percent of time during which there is electrographic seizure activity from IP initiation to 72 hours. The change from baseline of seizure burden was summarized using descriptive statistics by treatment group. The baseline seizure burden is defined for 30 minutes prior to IP initiation.	Up to 72 hours after IP initiation

Collaborators and Investigators

• Sponsor: Marinus Pharmaceuticals
• Investigators: Study Director: Maciej Gasior, MD, PhD, Marinus Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2020
• Primary Completion (Actual): March 30, 2024
• Study Completion (Actual): April 28, 2024

Study Registration Dates

• First Submitted: April 30, 2020
• First Submitted That Met QC Criteria: May 12, 2020
• First Posted (Actual): May 18, 2020

Study Record Updates

• Last Update Posted (Actual): May 29, 2025
• Last Update Submitted That Met QC Criteria: May 12, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Epilepsy; Status Epilepticus; Seizure; Convulsive Status Epilepticus; Non-Convulsive Status Epilepticus
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Seizures; Status Epilepticus; Neurosteroids; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; GABA Modulators; GABA Agents; Ganaxolone
• Other Study ID Numbers: 1042-SE-3003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No