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

NCT05814523 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: 1042-SE-3004
• Study Type: interventional
• Target: N/A
• Locations: 16 countries
• Sites: 52

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

Keywords

Refractory status epilepticus; Ganaxolone; Antiepileptic drug; Standard of care

Outcome Measures

Primary Outcomes (2)

• Percentage of participants who will report cessation of SE within 30 minutes of investigational product (IP) initiation of at least 30 minutes duration

  Status epilepticus cessation will be determined by the investigator based on clinical and electroencephalography (EEG) features

  Up to 30 minutes

• Percentage of participants who will report no escalation of treatment for persistent or recurrent SE within 36 hours of IP initiation

  Up to 36 hours

Secondary Outcomes (23)

• Percentage of participants who will report cessation of SE within 30 minutes of IP initiation of at least 30 minutes duration

  Up to 30 minutes

• Percentage of participants who will report no escalation of treatment for persistent or recurrent SE within 72 hours of IP initiation

  Up to 72 hours

• Time to SE cessation

  Up to 72 hours

• Percentage of participants having cessation of SE within 30 minutes of IP initiation of at least 30 minutes duration without escalation of treatment

  Up to 30 minutes

• Percentage of participants reporting no escalation of treatment for persistent or recurrent SE within 36 hours of IP initiation

  Up to 36 hours

Study Arms (2)

Ganaxolone IV solution + SOC IV AED

EXPERIMENTAL

Drug: Ganaxolone; Drug: Standard of care

Placebo IV solution + SOC IV AED

EXPERIMENTAL

Drug: Placebo; Drug: Standard of care

Interventions

Ganaxolone DRUG

Ganaxolone will be administered as IV solution.

Ganaxolone IV solution + SOC IV AED

Placebo DRUG

Placebo will be administered as IV solution.

Placebo IV solution + SOC IV AED

Standard of care 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.

Ganaxolone IV solution + SOC IV AED; Placebo IV solution + SOC IV AED

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• Life expectancy of less than 24 hours.
• 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).
• 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.
• Clinical condition or advance directive that would NOT permit admission to the ICU or use of IV anesthesia.
• Participants known or suspected to be pregnant
• Participants with known allergy or sensitivity to progesterone or allopregnanolone medications/supplements
• Receiving a concomitant IV product containing Captisol.
• Known or suspected hepatic insufficiency or hepatic failure leading to impaired synthetic liver function.
• 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.
• 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 a 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

Study Sites (52)

Medical University of Innsbruck

Innsbruck, A-6020, Austria

Location

Kepler University Hospital

Linz, 4020, Austria

Location

Kepler Universitätsklinikum GmbH

Linz, 4021, Austria

Location

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

Salzburg, A-5020, Austria

Location

Medical University Vienna

Vienna, A-1090, Austria

Location

Hôpital Universitaire de Bruxelles - Hôpital Erasme

Brussels, 1070, Belgium

Location

UZA University Hospital Antwerpen

Edegem, 2650, Belgium

Location

University Hospitals Leuven

Leuven, 3000, Belgium

Location

Dubrava University Hospital

Zagreb, 10000, Croatia

Location

University Hospital Centre Zagreb

Zagreb, 10000, Croatia

Location

Mazaryk University, Brno,The First Department of Neurology

Brno, 60200, Czechia

Location

University Hospital Ostrava

Ostrava, 70852, Czechia

Location

Motol University Hospital

Prague, 150 06, Czechia

Location

Helsinki University Hospital

Helsinki, 00290, Finland

Location

Kuopio University Hospital

Kuopio, 70210, Finland

Location

Hopital R. Salengro

Lille, 59037, France

Location

Hospices Civils de Lyon

Lyon, 69002, France

Location

CHRU Nancy

Nancy, 54000, France

Location

Chu de Toulouse

Toulouse, 31059, France

Location

University of Osnabruck, Dep of Neurology, Osnabrück

Osnabrück, Osnabruck, 49074, Germany

Location

Universitätsklinikum Erlangen

Erlangen, 91054, Germany

Location

Epilepsy Center Hessen

Marburg, 35043, Germany

Location

Universität- und Rehabilitationskliniken Ulm, RKU

Ulm, 898081, Germany

Location

National Institute of Clinical Neurosciences

Budapest, 1145, Hungary

Location

Soroka Medical Center

Beersheba, Beer-Sheva, 8410100, Israel

Location

Hadassah Medical Center

Jerusalem, 12000, Israel

Location

Sheba Medical Center

Tel Aviv, 52621, Israel

Location

Tel-Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Azienda Ospedaliero Universitaria Caregg

Florence, 50134, Italy

Location

Università Cattolica del Sacro Cuore

Milan, 20123, Italy

Location

Azienda Ospedaliera Universitaria di Modena

Modena, 41100, Italy

Location

Azienda Ospedaliera Universitaria Integrata di Verona

Verona, 37126, Italy

Location

Vilnius University Hospital Santaros Klinikos

Vilnius, 08661, Lithuania

Location

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

Katowice, Katowice-Ochojec, 40-635, Poland

Location

Oddzial Kliniczny Neurologii, Szpital Uniwersytecki w Krakowie

Krakow, Krakow, 30-688, Poland

Location

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

Katowice, 40-752, Poland

Location

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

Katowice, 41-800, Poland

Location

Samodzielny Publiczny Szpital Kliniczny

Lublin, 20-954, Poland

Location

WSS im Gromkowskiego

Wroclaw, 51-149, Poland

Location

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

Banská Bystrica, 975 17, Slovakia

Location

SlovakiaNeurologická klinika SZU a UNB Nemocnica Ružinov Univerzitná nemocnica Bratislava

Bratislava, 826 06, Slovakia

Location

Neurologické oddelenie Nemocnica Agel Levoča a.s.

Levoča, 054 01, Slovakia

Location

Neurologické oddelenie Fakultná nemocnica

Trnava, 917 01, Slovakia

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08004, Spain

Location

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

Barcelona, 08041, Spain

Location

Hospital Clinico San Carlos Madrid.

Madrid, 28040, Spain

Location

Hospital Regional Universitario de Málaga

Málaga, 29010, Spain

Location

Hôpitaux Universitaires de Genève (HUG)

Geneva, 1205, Switzerland

Location

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, 1011, Switzerland

Location

Cardiff and Vale UHB

Cardiff, CF14 4W, United Kingdom

Location

King's College Hospital, Department of Neurology

London, United Kingdom

Location

Oxford University Hospitals NHS Foundation Trust

Oxford, OX3 9DU, United Kingdom

Location

MeSH Terms

Conditions

Status Epilepticus

Interventions

ganaxolone; Standard of Care

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2023
• First Posted: April 18, 2023
• Study Start: March 1, 2024
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: May 14, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

IL (4); HU (1); CH (2); IT (4); GB (3); AU (5); SL (4); LI (1); DE (4); FR (4); CZ (3); CR (2); FI (2); BE (3); PL (6); ES (4)