Randomized Therapy In Status Epilepticus (RAISE)

• ClinicalTrials.gov Identifier: NCT04391569
• Recruitment Status: Recruiting
• First Posted: May 18, 2020
• Last Update Posted: February 23, 2023
• Sponsor: Marinus Pharmaceuticals
• Information provided by (Responsible Party): Marinus Pharmaceuticals

Tracking Information

• First Submitted Date: April 30, 2020
• First Posted Date: May 18, 2020
• Last Update Posted Date: February 23, 2023
• Actual Study Start Date: October 10, 2020
• Estimated Primary Completion Date: October 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 24, 2023)

• Percentage of participants reporting SE cessation within 30 minutes of IP initiation without medications for the acute treatment of SE [ Time Frame: Up to 30 minutes ]
  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.
• Percentage of participants with no progression to IV anesthesia for 36 hours following IP initiation [ Time Frame: Up to 36 hours ]

Original Primary Outcome Measures (submitted: May 12, 2020)

• SE Cessation [ Time Frame: 30 minutes ]
  Proportion of participants with status epilepticus cessation within 30 minutes of IP initiation without medications for the acute treatment of status epilepticus. SE cessation is determined by clinical and EEG findings.
• Progression to IV anesthesia [ Time Frame: 36 hours ]
  Proportion of participants with no progression to IV anesthesia for 36 hours following IP initiation

Current Secondary Outcome Measures (submitted: January 24, 2023)

• Percentage of participants with no progression to IV anesthesia for 72 hours following IP initiation [ Time Frame: Up to 72 hours ]
• Time to SE Cessation following IP initiation [ Time Frame: Up to 48 hours ]

Original Secondary Outcome Measures (submitted: May 12, 2020)

• Progression to IV anesthesia [ Time Frame: 72 hours ]
  No progression to IV anesthesia for 72 hours following IP initiation
• SE Cessation [ Time Frame: 48 hours ]
  Time to SE cessation following IP initiation

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Brief Summary: This study will evaluate 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 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Status Epilepticus

Intervention

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

Study Arms

• Placebo Comparator: IV Placebo
  Placebo bolus dose followed by continuous infusion for 36 hours, followed by 12 hour taper
  Intervention: Drug: Placebo
• Experimental: IV ganaxolone active
  Ganaxolone bolus dose followed by continuous infusion for 36 hours, followed by 12 hour taper
  Intervention: Drug: Ganaxolone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 9, 2020): 124
• Original Estimated Enrollment (submitted: May 12, 2020): 168
• Estimated Study Completion Date: October 31, 2023
• Estimated Primary Completion Date: October 31, 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Marinus; clinicaltrials@marinuspharma.com

• Listed Location Countries: Australia, Canada, United States

Administrative Information

• NCT Number: NCT04391569
• Other Study ID Numbers: 1042-SE-3003
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Marinus Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Marinus Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Marinus Pharmaceuticals
• Verification Date: February 2023