Randomized Therapy In Status Epilepticus

Status Epilepticus Clinical Trial

— RAISE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04391569
• Other study ID #: 1042-SE-3003
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 10, 2020
• Est. completion date: November 30, 2024

Study information

• Verified date: May 2024
• Source: Marinus Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

This is a double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of IV ganaxolone in status epilepticus. Investigational product will be 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 will be screened for inclusion/exclusion criteria prior to receiving investigational product by continuous IV infusion. Participants will be followed for approximately 4 weeks. Participants who are known to be at risk for SE may be consented or assented prior to an SE event.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 124
• Est. completion date: November 30, 2024
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Status Epilepticus

Intervention

Drug:
• Ganaxolone
Ganaxolone will be administered.
• Placebo
Placebo will be administered.

Locations

Country	Name	City	State
Australia	Marinus Research Site	Box Hill	Victoria
Australia	Marinus Research Site	Melbourne	Victoria
Australia	Marinus Research Site	Melbourne	Victoria
Australia	Marinus Research Site	Randwick	New South Wales
Australia	Marinus Research Site	South Brisbane	Queensland
Canada	Marinus Research Site	Calgary	Alberta
Canada	Marinus Research Site	Calgary	Alberta
Canada	Marinus Research Site	Kingston	Ontario
Canada	Marinus Research Site	Quebec City	Quebec
Canada	Marinus Research Site	Saskatoon	Saskatchewan
United States	Marinus Research Site	Albany	New York
United States	Marinus Research Site	Albuquerque	New Mexico
United States	Marinus Research Site	Ann Arbor	Michigan
United States	Marinus Research Site	Aurora	Colorado
United States	Marinus Research Site	Baltimore	Maryland
United States	Marinus Research Site	Baltimore	Maryland
United States	Marinus Research Site #1	Baltimore	Maryland
United States	Marinus Research Site	Birmingham	Alabama
United States	Marinus Research Site	Boston	Massachusetts
United States	Marinus Research Site	Boston	Massachusetts
United States	Marinus Research Site	Boston	Massachusetts
United States	Marinus Research Site	Boston	Massachusetts
United States	Marinus Research Site	Boston	Massachusetts
United States	Marinus Research Site	Brooklyn	New York
United States	Marinus Research Site	Chapel Hill	North Carolina
United States	Marinus Research Site	Charlotte	North Carolina
United States	Marinus Research Site	Chicago	Illinois
United States	Marinus Research Site	Chicago	Illinois
United States	Marinus Research Site	Cincinnati	Ohio
United States	Marinus Research Site	Cleveland	Ohio
United States	Marinus Research Site	Columbia	Missouri
United States	Marinus Research Site	Columbus	Ohio
United States	Marinus Research Site	Dallas	Texas
United States	Marinus Research Site	Denver	Colorado
United States	Marinus Research Site	Downey	California
United States	Marinus Research Site	Durham	North Carolina
United States	Marinus Research Site	Fort Worth	Texas
United States	Marinus Research Site	Gainesville	Florida
United States	Marinus Research Site	Grand Rapids	Michigan
United States	Marinus Research Site	Knoxville	Tennessee
United States	Marinus Research Site	La Jolla	California
United States	Marinus Research Site	Little Rock	Arkansas
United States	Marinus Research Site	Louisville	Kentucky
United States	Marinus Research Site	Madison	Wisconsin
United States	Marinus Research Site	Memphis	Tennessee
United States	Marinus Research Site	Miami	Florida
United States	Marinus Research Site	Miami	Florida
United States	Marinus Research Site #1	Miami	Florida
United States	Marinus Research Site	Murray	Utah
United States	Marinus Research Site	New Brunswick	New Jersey
United States	Marinus Research Site	New Haven	Connecticut
United States	Marinus Research Site	New Orleans	Louisiana
United States	Marinus Research Site	New York	New York
United States	Marinus Research Site	New York	New York
United States	Marinus Research Site	Orange	California
United States	Marinus Research Site	Philadelphia	Pennsylvania
United States	Marinus Research Site	Philadelphia	Pennsylvania
United States	Marinus Research Site	Philadelphia	Pennsylvania
United States	Marinus Research Site #1	Philadelphia	Pennsylvania
United States	Marinus Research Site #2	Philadelphia	Pennsylvania
United States	Marinus Research Site	Phoenix	Arizona
United States	Marinus Research Site	Pittsburgh	Pennsylvania
United States	Marinus Research Site	Port Saint Lucie	Florida
United States	Marinus Research Site	Portland	Oregon
United States	Marinus Research Site	Portland	Oregon
United States	Marinus Research Site	Richmond	Virginia
United States	Marinus Research Site	Rochester	New York
United States	Marinus Research Site	Sacramento	California
United States	Marinus Research Site	Saint Louis	Missouri
United States	Marinus Research Site	San Antonio	Texas
United States	Marinus Research Site	Shreveport	Louisiana
United States	Marinus Research Site	Tampa	Florida
United States	Marinus Research Site	Urbana	Illinois
United States	Marinus Research Site	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Marinus Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants reporting SE cessation within 30 minutes of IP initiation without medications for the acute treatment of SE	SE cessation will be determined by the investigator based on clinical and electroencephalography (EEG). Medications for the acute treatment of SE are defined as AEDs administered to abort ongoing SE or prevent imminent recurrence of SE based on clinical or EEG evidence.	Up to 30 minutes
Primary	Percentage of participants with no progression to IV anesthesia for 36 hours following IP initiation		Up to 36 hours
Secondary	Percentage of participants with no progression to IV anesthesia for 72 hours following IP initiation		Up to 72 hours
Secondary	Time to SE Cessation following IP initiation		Up to 48 hours