Clinical trial NCT04391569: Randomized Therapy In Status Epilepticus
Official title: A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy and Safety of Intravenous Ganaxolone in Status Epilepticus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Status Epilepticus
Keywords: Seizure
Status Epilepticus
Convulsive Status Epilepticus
Non-Convulsive Status Epilepticus
Epilepsy
Lead sponsor: Marinus Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-05-18
Enrollment: 100
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With SE Cessation Within 30 Minutes of Investigational Product (IP) Initiation Without Medications for the Acute Treatment of SE
timeFrame: Up to 30 minutes
measure: Percentage of Participants With no Progression to Intravenous (IV) Anesthesia for 36 Hours Following Investigational Product (IP) Initiation
timeFrame: Up to 36 hours after IP initiation
measure: Number of Participants With Treatment Emergent Adverse Events
timeFrame: Up to 4 weeks after IP initiation
Secondary outcomes:
measure: Percentage of Participants With no Progression to IV Anesthesia for 72 Hours Following IP Initiation
timeFrame: Up to 72 hours after IP initiation
measure: Time to SE Cessation Following IP Initiation
timeFrame: Up to 72 hours after IP initiation
measure: Percentage of Participants With Any Escalation of Treatment in the First 24 Hours Following IP Initiation
timeFrame: Up to 24 hours after IP initiation
measure: Time to Treatment Escalation in the First 24 Hours Following IP Initiation
timeFrame: Up to 24 hours after IP initiation
measure: Time to Initiation of Anesthesia for SE Treatment Through the Final Study Follow-up Visit/Contact
timeFrame: Up to 4 Weeks following IP initiation
measure: Percentage of Participants Who Develop Super Refractory Status Epilepticus (SRSE) Through the Final Study Follow-up Visit/Contact
timeFrame: Up to 4 Weeks following IP initiation
measure: Percent Change From Baseline in Seizure Burden Through 72 Hours Following IP Initiation
timeFrame: Up to 72 hours after IP initiation
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Marinus Research Site
state: Alabama
city: Phoenix
country: United States
facility: Marinus Research Site
state: Arizona
city: Little Rock
country: United States
facility: Marinus Research Site
state: Arkansas
city: Downey
country: United States
facility: Marinus Research Site
state: California
city: La Jolla
country: United States
facility: Marinus Research Site
state: California
city: Orange
country: United States
facility: Marinus Research Site
state: California
city: Sacramento
country: United States
facility: Marinus Research Site
state: California
city: Aurora
country: United States
facility: Marinus Research Site
state: Colorado
city: Denver
country: United States
facility: Marinus Research Site
state: Colorado
city: New Haven
country: United States
facility: Marinus Research Site
state: Connecticut
city: Gainesville
country: United States
facility: Marinus Research Site
state: Florida
city: Miami
country: United States
facility: Marinus Research Site #1
state: Florida
city: Miami
country: United States
facility: Marinus Research Site
state: Florida
city: Miami
country: United States
facility: Marinus Research Site
state: Florida
city: Port Saint Lucie
country: United States
facility: Marinus Research Site
state: Florida
city: Tampa
country: United States
facility: Marinus Research Site
state: Florida
city: Chicago
country: United States
facility: Marinus Research Site
state: Illinois
city: Chicago
country: United States
facility: Marinus Research Site
state: Illinois
city: Urbana
country: United States
facility: Marinus Research Site
state: Illinois
city: Louisville
country: United States
facility: Marinus Research Site
state: Kentucky
city: New Orleans
country: United States
facility: Marinus Research Site
state: Louisiana
city: Shreveport
country: United States
facility: Marinus Research Site
state: Louisiana
city: Baltimore
country: United States
facility: Marinus Research Site #1
state: Maryland
city: Baltimore
country: United States
facility: Marinus Research Site
state: Maryland
city: Baltimore
country: United States
facility: Marinus Research Site
state: Maryland
city: Boston
country: United States
facility: Marinus Research Site
state: Massachusetts
city: Boston
country: United States
facility: Marinus Research Site
state: Massachusetts
city: Boston
country: United States
facility: Marinus Research Site
state: Massachusetts
city: Boston
country: United States
facility: Marinus Research Site
state: Massachusetts
city: Boston
country: United States
facility: Marinus Research Site
state: Massachusetts
city: Worcester
country: United States
facility: Marinus Research Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Marinus Research Site
state: Michigan
city: Grand Rapids
country: United States
facility: Marinus Research Site
state: Michigan
city: Columbia
country: United States
facility: Marinus Research Site
state: Missouri
city: Saint Louis
country: United States
facility: Marinus Research Site
state: Missouri
city: New Brunswick
country: United States
facility: Marinus Research Site
state: New Jersey
city: Albuquerque
country: United States
facility: Marinus Research Site
state: New Mexico
city: Albany
country: United States
facility: Marinus Research Site
state: New York
city: Brooklyn
country: United States
facility: Marinus Research Site
state: New York
city: New York
country: United States
facility: Marinus Research Site
state: New York
city: New York
country: United States
facility: Marinus Research Site
state: New York
city: Rochester
country: United States
facility: Marinus Research Site
state: New York
city: Chapel Hill
country: United States
facility: Marinus Research Site
state: North Carolina
city: Charlotte
country: United States
facility: Marinus Research Site
state: North Carolina
city: Durham
country: United States
facility: Marinus Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Marinus Research Site
state: Ohio
city: Cleveland
country: United States
facility: Marinus Research Site
state: Ohio
city: Columbus
country: United States
facility: Marinus Research Site
state: Ohio
city: Portland
country: United States
facility: Marinus Research Site
state: Oregon
city: Portland
country: United States
facility: Marinus Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Marinus Research Site #1
state: Pennsylvania
city: Philadelphia
country: United States
facility: Marinus Research Site #2
state: Pennsylvania
city: Philadelphia
country: United States
facility: Marinus Research Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Marinus Research Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Marinus Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Marinus Research Site
state: Pennsylvania
city: Knoxville
country: United States
facility: Marinus Research Site
state: Tennessee
city: Memphis
country: United States
facility: Marinus Research Site
state: Tennessee
city: Dallas
country: United States
facility: Marinus Research Site
state: Texas
city: Fort Worth
country: United States
facility: Marinus Research Site
state: Texas
city: San Antonio
country: United States
facility: Marinus Research Site
state: Texas
city: Murray
country: United States
facility: Marinus Research Site
state: Utah
city: Richmond
country: United States
facility: Marinus Research Site
state: Virginia
city: Madison
country: United States
facility: Marinus Research Site
state: Wisconsin
city: Randwick
country: Australia
facility: Marinus Research Site
state: New South Wales
city: South Brisbane
country: Australia
facility: Marinus Research Site
state: Queensland
city: Box Hill
country: Australia
facility: Marinus Research Site
state: Victoria
city: Melbourne
country: Australia
facility: Marinus Research Site
state: Victoria
city: Melbourne
country: Australia
facility: Marinus Research Site
state: Victoria
city: Calgary
country: Canada
facility: Marinus Research Site
state: Alberta
city: Calgary
country: Canada
facility: Marinus Research Site
state: Alberta
city: Kingston
country: Canada
facility: Marinus Research Site
state: Ontario
city: Quebec City
country: Canada
facility: Marinus Research Site
state: Quebec
city: Saskatoon
country: Canada
facility: Marinus Research Site
state: Saskatchewan
Study officials:
References: