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

NCT05757544 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 1042-SE-2002
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Status Epilepticus

Keywords

Established status epilepticus; Ganaxolone; Antiepileptic drug; Adjuvant therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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 during IP infusion

  Up to Day 7

• 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

Study Arms (3)

Dose optimization phase (open label): IV Ganaxolone bolus (variable) followed by infusion (variable)

EXPERIMENTAL

Drug: IV Ganaxolone

Double-blind phase: IV Ganaxolone + SOC

EXPERIMENTAL

Drug: IV Ganaxolone

Double-blind phase: IV Placebo + SOC

PLACEBO COMPARATOR

Drug: IV Placebo

Interventions

IV Ganaxolone DRUG

IV Ganaxolone will be administered.

Dose optimization phase (open label): IV Ganaxolone bolus (variable) followed by infusion (variable); Double-blind phase: IV Ganaxolone + SOC

IV Placebo DRUG

IV Placebo will be administered

Double-blind phase: IV Placebo + SOC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females at least 18 years of age at the time of the first IP bolus dose.
• Has received benzodiazepines before or after arrival to the ED for generalized convulsive seizures lasting more than 5 minutes.
• Has received the last dose of benzodiazepine more than 5 minutes prior to the first IP bolus initiation.
• Ongoing or recurrent convulsions, or evidence of electrographic SE on rapid EEG immediately prior to the first IP bolus initiation.
• 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).

You may not qualify if:

• The participant is intubated or the decision to proceed with intubation has been made.
• The cause of SE is acute anoxic brain injury, cardiac arrest, acute trauma, hyper- or hypo-glycemia, or eclampsia.
• The participant is known or suspected to be pregnant.
• The participant is incarcerated at the time of SE occurrence.
• Participants who pre-emptively opted out of the study.
• A known allergy or sensitivity to progesterone or allopregnanolone medications/ supplements.
• Receiving a concomitant IV product containing Captisol®.
• 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).
• Individual weighing or suspected to weigh \<40 kilograms (kg).
• Hypotension requiring 2 or more vasopressors.
• An individual who, in the opinion of the investigator has a life expectancy of less than 24 hours.
• 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.
• 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.

Sponsors & Collaborators

• Marinus Pharmaceuticals: lead

MeSH Terms

Conditions

Status Epilepticus

Interventions

ganaxolone

Condition Hierarchy (Ancestors)

Seizures; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: All participating staff involved in the evaluation and execution of the study will remain blinded to the participant's treatment assignment during the double-blind phase.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2023
• First Posted: March 7, 2023
• Study Start: April 1, 2023
• Primary Completion: February 1, 2026
• Study Completion: February 1, 2026
• Last Updated: May 7, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share