To Evaluate the Efficacy, Safety, and Tolerability of Intravenous Ganaxolone Added to Standard of Care in Refractory Status Epilepticus (RSE)

NCT ID: NCT05814523

Last Updated: 2024-05-14

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-31
• Study Completion Date: 2024-08-31

Brief Summary

This is a multicenter, double-blind, randomized, placebo-controlled study that will evaluate the efficacy, safety, and tolerability of intravenous (IV) ganaxolone versus placebo co-administered with IV antiepileptic drug (AED) according to standard of care for the treatment of RSE. Approximately 70 participants will be randomized in a 1:1 ratio to receive ganaxolone IV solution or placebo IV solution along with standard of care (SOC) IV AED.

Conditions

Refractory Status Epilepticus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ganaxolone IV solution + SOC IV AED

Group Type: EXPERIMENTAL

Ganaxolone

Intervention Type: DRUG

Ganaxolone will be administered as IV solution.

Standard of care

Intervention Type: DRUG

A non-anesthetic medication not previously used for treatment of SE within the current episode and will be administered at a dose sufficient for the termination of SE according to investigator judgment.

Placebo IV solution + SOC IV AED

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Placebo will be administered as IV solution.

Standard of care

Intervention Type: DRUG

A non-anesthetic medication not previously used for treatment of SE within the current episode and will be administered at a dose sufficient for the termination of SE according to investigator judgment.

Interventions

Ganaxolone

Ganaxolone will be administered as IV solution.

Intervention Type: DRUG

Placebo

Placebo will be administered as IV solution.

Intervention Type: DRUG

Standard of care

A non-anesthetic medication not previously used for treatment of SE within the current episode and will be administered at a dose sufficient for the termination of SE according to investigator judgment.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Participant, participant's parent, guardian, or LAR must provide signed 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 participant.

2. Male or females 18 years of age and older at the time of the first dose of IP.

3. SE warranting imminent progression of treatment meeting the following criteria:

a) A diagnosis of SE, warranting imminent progression of treatment for seizure control, 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.

4. Participants must have received a benzodiazepine and at least 1 of the following IV AEDs for treatment of the current episode of SE administered at an adequate dose and for a sufficient duration, in the judgement of the investigator, to demonstrate efficacy. The benzodiazepine and at least 1 of the IV AEDs must have been administered at a dose that would be expected to be effective for the termination of the current episode of SE.

• 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 (eg, hypoglycemia < 50 milligrams per deciliter [mg/dL] or hyperglycemia > 400 mg/dL).

3. Participants who have received high-dose IV anesthetics (eg, 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 admission to the ICU or 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 milliliters per minute per 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.

11. Known or suspected history or evidence of a medical condition that, in the investigator's judgment, would expose a participant to an undue risk of a significant adverse event or interfere with assessments of safety or efficacy during the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Marinus Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Medical University of Innsbruck

Innsbruck, , Austria

Kepler University Hospital

Linz, , Austria

Kepler Universitätsklinikum GmbH

Linz, , Austria

Paracelsus Medical University Salzburg, Christian Doppler University Hospital, Department of Neurology

Salzburg, , Austria

Medical University Vienna

Vienna, , Austria

Hôpital Universitaire de Bruxelles - Hôpital Erasme

Brussels, , Belgium

UZA University Hospital Antwerpen

Edegem, , Belgium

University Hospitals Leuven

Leuven, , Belgium

Dubrava University Hospital

Zagreb, , Croatia

University Hospital Centre Zagreb

Zagreb, , Croatia

Mazaryk University, Brno,The First Department of Neurology

Brno, , Czechia

University Hospital Ostrava

Ostrava, , Czechia

Motol University Hospital

Prague, , Czechia

Helsinki University Hospital

Helsinki, , Finland

Kuopio University Hospital

Kuopio, , Finland

Hopital R. Salengro

Lille, , France

Hospices Civils de Lyon

Lyon, , France

CHRU Nancy

Nancy, , France

Chu de Toulouse

Toulouse, , France

University of Osnabruck, Dep of Neurology, Osnabrück

Osnabrück, Osnabruck, Germany

Universitätsklinikum Erlangen

Erlangen, , Germany

Epilepsy Center Hessen

Marburg, , Germany

Universität- und Rehabilitationskliniken Ulm, RKU

Ulm, , Germany

National Institute of Clinical Neurosciences

Budapest, , Hungary

Soroka Medical Center

Beersheba, Beer-Sheva, Israel

Hadassah Medical Center

Jerusalem, , Israel

Sheba Medical Center

Tel Aviv, , Israel

Tel-Aviv Sourasky Medical Center

Tel Aviv, , Israel

Azienda Ospedaliero Universitaria Caregg

Florence, , Italy

Università Cattolica del Sacro Cuore

Milan, , Italy

Azienda Ospedaliera Universitaria di Modena

Modena, , Italy

Azienda Ospedaliera Universitaria Integrata di Verona

Verona, , Italy

Vilnius University Hospital Santaros Klinikos

Vilnius, , Lithuania

Oddział Neurologii z Pododdziałem Udarowym Górnośląskie Centrum Medyczne im. prof. Leszka Gieca Śląskiego Uniwersytetu Medycznego w Katowicach

Katowice, Katowice-Ochojec, Poland

Oddzial Kliniczny Neurologii, Szpital Uniwersytecki w Krakowie

Krakow, Krakow, Poland

Uniwersyteckie Centrum Kliniczne im. prof. K. Gibińskiego w Katowicach

Katowice, , Poland

Samodzielny Publiczny Szpital Kliniczny Nr 1 im. Prof. Stanisława Szyszko Śląskiego Uniwersytetu

Katowice, , Poland

Samodzielny Publiczny Szpital Kliniczny

Lublin, , Poland

WSS im Gromkowskiego

Wroclaw, , Poland

II. Neurologická klinika SZU Fakultná nemocnica s poliklinikou F. D. Roosevelta Banská Bystrica

Banská Bystrica, , Slovakia

SlovakiaNeurologická klinika SZU a UNB Nemocnica Ružinov Univerzitná nemocnica Bratislava

Bratislava, , Slovakia

Neurologické oddelenie Nemocnica Agel Levoča a.s.

Levoča, , Slovakia

Neurologické oddelenie Fakultná nemocnica

Trnava, , Slovakia

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Santa Creu i Sant Pau, Institut de Recerca Biomedica Sant Pau

Barcelona, , Spain

Hospital Clinico San Carlos Madrid.

Madrid, , Spain

Hospital Regional Universitario de Málaga

Málaga, , Spain

Hôpitaux Universitaires de Genève (HUG)

Geneva, , Switzerland

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, , Switzerland

Cardiff and Vale UHB

Cardiff, , United Kingdom

King's College Hospital, Department of Neurology

London, , United Kingdom

Oxford University Hospitals NHS Foundation Trust

Oxford, , United Kingdom

Countries

Austria; Belgium; Croatia; Czechia; Finland; France; Germany; Hungary; Israel; Italy; Lithuania; Poland; Slovakia; Spain; Switzerland; United Kingdom

Other Identifiers

1042-SE-3004

Identifier Type: -

Identifier Source: org_study_id