Safety and Efficacy Study of IV Ganaxolone as Adjuvant Therapy for Established Status Epilepticus (ESE)

A Study to Optimize the Dosing Regimen and Assess Safety and Efficacy of IV Ganaxolone as Adjuvant Therapy for Established Status Epilepticus

This study is designed to optimize the dosing regimen and evaluate the preliminary safety and efficacy of Intravenous (IV) ganaxolone as adjuvant therapy for participants with ESE receiving initial IV antiepileptic drug (AED) according to currently practiced standard of care (SOC). The study will be composed of 2 phases: an initial, open-label, dose optimization phase followed by IV ganaxolone versus placebo double-blind phase.

Study Overview

• Status: Withdrawn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

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Not yet recruiting
      • Marinus Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Recruiting
      • Marinus Research Site
    • Columbus, Ohio, United States, 43210
      • Not yet recruiting
      • Marinus Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males or females at least 18 years of age at the time of the first IP bolus dose.
2. Has received benzodiazepines before or after arrival to the ED for generalized convulsive seizures lasting more than 5 minutes.
3. Has received the last dose of benzodiazepine more than 5 minutes prior to the first IP bolus initiation.
4. Ongoing or recurrent convulsions, or evidence of electrographic SE on rapid EEG immediately prior to the first IP bolus initiation.
5. The participant has not yet received a second-line IV AED for the treatment of the current episode of SE or the first IP bolus can be initiated within 15 minutes before or 10 minutes after the administration of such IV AED(s).

Exclusion Criteria:

1. The participant is intubated or the decision to proceed with intubation has been made.
2. The cause of SE is acute anoxic brain injury, cardiac arrest, acute trauma, hyper- or hypo-glycemia, or eclampsia.
3. The participant is known or suspected to be pregnant.
4. The participant is incarcerated at the time of SE occurrence.
5. Participants who pre-emptively opted out of the study.
6. A known allergy or sensitivity to progesterone or allopregnanolone medications/ supplements.
7. Receiving a concomitant IV product containing Captisol®.
8. Known estimated glomerular filtration rate (eGFR) <30 milliliters per minute (mL/min) and not receiving dialysis (may initiate first IP bolus prior to acute labs).
9. Individual weighing or suspected to weigh <40 kilograms (kg).
10. Hypotension requiring 2 or more vasopressors.
11. An individual who, in the opinion of the investigator has a life expectancy of less than 24 hours.
12. 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.
13. Known or suspected history or evidence of a medical condition that, in the investigator's judgment, would expose participant to an undue risk of a significant adverse event or interfere with assessments of safety or efficacy during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Double-blind phase: IV Ganaxolone + SOC	Drug: IV Ganaxolone; IV Ganaxolone will be administered.
Placebo Comparator: Double-blind phase: IV Placebo + SOC	Drug: IV Placebo; IV Placebo will be administered
Experimental: Dose optimization phase (open label): IV Ganaxolone bolus (variable) followed by infusion (variable)	Drug: IV Ganaxolone; IV Ganaxolone will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Absence of electrographic (rapid electroencephalography [EEG]) evidence of status epilepticus or recurrence of convulsions at 1 hour after the first IP bolus administration without the use of any additional medications with anti-seizure properties	At 1 hour

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of participants with no escalation to IV anesthesia for treatment of seizures during IP infusion	Up to Day 7
Percentage of participants with no escalation of care for Status epilepticus (SE) during investigational product (IP) infusion	Up to Day 7
Time to clinical seizure and electrographic SE cessation	Up to Day 7
Percentage of participants with no escalation of care (including re-administration of IP) at any point within 24 hours from the initial IP bolus administration	Up to 24 hours
Percentage of participants with no escalation to IV anesthesia for treatment of seizures within 24 hours of the initial IP bolus	Up to 24 hours
Time to clinical or electrographic seizure recurrence within 24 hours from the initiation of the first IP bolus	Up to 24 hours

Collaborators and Investigators

• Sponsor: Marinus Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: February 24, 2023
• First Submitted That Met QC Criteria: February 24, 2023
• First Posted (Actual): March 7, 2023

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Antiepileptic drug; Adjuvant therapy; Ganaxolone; Established status epilepticus
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Seizures; Status Epilepticus; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; GABA Modulators; GABA Agents; Neurosteroids; Ganaxolone
• Other Study ID Numbers: 1042-SE-2002

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