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Refractory Status EpilepticusPhase 3NCT05814523

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

A Phase 3 study testing Ganaxolone in people with Refractory Status Epilepticus, run by Marinus Pharmaceuticals at 52 sites in 16 countries.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Refractory Status Epilepticus
What is being tested?
Ganaxolone
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
52 sitesin 16 countries
Study dates
Mar 2024to Aug 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 diagnosis of SE, warranting imminent progression of treatment for seizure control, with or without prominent motor features based on clinical and EEG findings:
  • Diagnosis is established by:
  • For SE with prominent motor features: Clinical and EEG seizure activity indicative of convulsive, myoclonic, or focal motor SE.
Show all 17Show fewer
  • For SE without prominent motor features (nonconvulsive SE): Appropriate clinical features and an EEG indicative of non-convulsive status epilepticus (NCSE).
  • 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
  • IV Phenobarbital.
  • 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.

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

52 sites in 16 countries.

52 sites in 16 countries

Poland6 sites

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

    Katowice, Katowice-Ochojec, 40-635

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

    Katowice, 40-752

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

    Katowice, 41-800

  • Oddzial Kliniczny Neurologii, Szpital Uniwersytecki w Krakowie

    Krakow, Krakow, 30-688

  • Samodzielny Publiczny Szpital Kliniczny

    Lublin, 20-954

  • WSS im Gromkowskiego

    Wroclaw, 51-149

Other trials in Poland

Austria5 sites

  • Medical University of Innsbruck

    Innsbruck, A-6020

  • Kepler University Hospital

    Linz, 4020

  • Kepler Universitätsklinikum GmbH

    Linz, 4021

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

    Salzburg, A-5020

  • Medical University Vienna

    Vienna, A-1090

Other trials in Austria

France4 sites

  • Hopital R. Salengro

    Lille, 59037

  • Hospices Civils de Lyon

    Lyon, 69002

  • CHRU Nancy

    Nancy, 54000

  • Chu de Toulouse

    Toulouse, 31059

Other trials in France

Germany4 sites

  • Universitätsklinikum Erlangen

    Erlangen, 91054

  • Epilepsy Center Hessen

    Marburg, 35043

  • University of Osnabruck, Dep of Neurology, Osnabrück

    Osnabrück, Osnabruck, 49074

  • Universität- und Rehabilitationskliniken Ulm, RKU

    Ulm, 898081

Other trials in Germany

Israel4 sites

  • Soroka Medical Center

    Beersheba, Beer-Sheva, 8410100

  • Hadassah Medical Center

    Jerusalem, 12000

  • Sheba Medical Center

    Tel Aviv, 52621

  • Tel-Aviv Sourasky Medical Center

    Tel Aviv, 64239

Other trials in Israel

Italy4 sites

  • Azienda Ospedaliero Universitaria Caregg

    Florence, 50134

  • Università Cattolica del Sacro Cuore

    Milan, 20123

  • Azienda Ospedaliera Universitaria di Modena

    Modena, 41100

  • Azienda Ospedaliera Universitaria Integrata di Verona

    Verona, 37126

Other trials in Italy

Slovakia4 sites

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

    Banská Bystrica, 975 17

  • SlovakiaNeurologická klinika SZU a UNB Nemocnica Ružinov Univerzitná nemocnica Bratislava

    Bratislava, 826 06

  • Neurologické oddelenie Nemocnica Agel Levoča a.s.

    Levoča, 054 01

  • Neurologické oddelenie Fakultná nemocnica

    Trnava, 917 01

Other trials in Slovakia

Spain4 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08004

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

    Barcelona, 08041

  • Hospital Clinico San Carlos Madrid.

    Madrid, 28040

  • Hospital Regional Universitario de Málaga

    Málaga, 29010

Other trials in Spain

Belgium3 sites

  • Hôpital Universitaire de Bruxelles - Hôpital Erasme

    Brussels, 1070

  • UZA University Hospital Antwerpen

    Edegem, 2650

  • University Hospitals Leuven

    Leuven, 3000

Other trials in Belgium

Czechia3 sites

  • Mazaryk University, Brno,The First Department of Neurology

    Brno, 60200

  • University Hospital Ostrava

    Ostrava, 70852

  • Motol University Hospital

    Prague, 150 06

Other trials in Czechia

United Kingdom3 sites

  • Cardiff and Vale UHB

    Cardiff, CF14 4W

  • King's College Hospital, Department of Neurology

    London

  • Oxford University Hospitals NHS Foundation Trust

    Oxford, OX3 9DU

Other trials in United Kingdom

Croatia2 sites

  • Dubrava University Hospital

    Zagreb, 10000

  • University Hospital Centre Zagreb

    Zagreb, 10000

Other trials in Croatia

Finland2 sites

  • Helsinki University Hospital

    Helsinki, 00290

  • Kuopio University Hospital

    Kuopio, 70210

Other trials in Finland

Switzerland2 sites

  • Hôpitaux Universitaires de Genève (HUG)

    Geneva, 1205

  • Centre Hospitalier Universitaire Vaudois (CHUV)

    Lausanne, 1011

Other trials in Switzerland

Hungary1 site

  • National Institute of Clinical Neurosciences

    Budapest, 1145

Other trials in Hungary

Lithuania1 site

  • Vilnius University Hospital Santaros Klinikos

    Vilnius, 08661

Other trials in Lithuania

About this study

Official title: A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Intravenous Ganaxolone Added to Standard of Care in Refractory Status Epilepticus

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.

Being tested
Ganaxolone, Placebo, Standard of care
Keywords
Refractory status epilepticus, Ganaxolone, Antiepileptic drug, Standard of care
Medical subject headings
Status Epilepticus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GanaxoloneDrug

    Ganaxolone will be administered as IV solution.

  • PlaceboDrug

    Placebo will be administered as IV solution.

  • Standard of careDrug

    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.

Study groups in NCT05814523
Study groupRoleWhat they receive
Ganaxolone IV solution + SOC IV AEDExperimentalNot described
Receives: Drug: Ganaxolone; Drug: Standard of care
Placebo IV solution + SOC IV AEDExperimentalNot described
Receives: Drug: Placebo; Drug: Standard of care

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Up to 30 minutes

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

    Measured: Up to 36 hours

Secondary outcomes (23)

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

    Measured: Up to 30 minutes

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

    Measured: Up to 72 hours

  3. Time to SE cessation

    Measured: Up to 72 hours

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

    Measured: Up to 30 minutes

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

    Measured: Up to 36 hours

  6. Percentage of participants reporting no escalation of treatment for persistent or recurrent SE within 72 hours of IP initiation

    Measured: Up to 72 hours

  7. Change from Baseline in Modified Rankin Scale (mRS) at the time of hospital discharge

    The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6, running from perfect health without symptoms to death where 0 - No symptoms; 1=No significant disability. Able to carry out all usual activities, despite some symptoms; 2=Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities; 3=Moderate disability. Requires some help, but able to walk unassisted; 4=Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted; 5=Severe disability. Requires constant nursing care and attention, bedridden, incontinent; 6=Dead. Higher scores will indicate high degree of disability.

    Measured: Baseline and Up to Day 31

  8. Change from Baseline in level of responsiveness as assessed by the Full Outline of UnResponsiveness (FOUR) Score scale

    The FOUR Score is a 17-point scale (with potential scores ranging from 0 - 16). Decreasing FOUR Score is associated with worsening level of consciousness. The FOUR coma scale includes 4 parameters with a minimum score of 0 and a maximum score of "4" for each of them: eye reactions (eye opening and tracking), motor responses (pain response and simple commands), stem reflexes (pupillary, corneal and cough) and respiratory patterns (respiratory rhythm and respiratory attempts in patients on a ventilator). The points are summed up, their sum is estimated. The interpretation of results will be as 15 to 16 score: clear consciousness; Less than 15: Impairment of consciousness; from 4 to 8: Coma and 0-4: Death. Lower the score, the greater the coma gravity.

    Measured: Baseline and at 24, 36 and 72 hours

  9. Change from Baseline in level of sedation/ agitation as assessed by Richmond Agitation and Sedation Scale (RASS)

    The RASS is a medical scale used to measure the agitation or sedation level. It is a 10-point scale that ranges from -5 to +4 with -5=unarousable and +4=combative. Zero means the patient is alert and calm. higher scores indicate more agitation.

    Measured: Baseline and at 24, 36 and 72 hours

  10. Percentage of participants with mRS > 3 at the time of hospital discharge

    The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The scale runs from 0-6, running from perfect health without symptoms to death where 0 - No symptoms; 1=No significant disability. Able to carry out all usual activities, despite some symptoms. 2=Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3=Moderate disability. Requires some help, but able to walk unassisted. 4=Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5=Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6=Dead. Higher scores will indicate high degree of disability.

    Measured: Up to 122 hours

  11. Change from Baseline in Clinical Global Impression-Improvement (CGI-I) following IP initiation and at hospital discharge

    The CGI-I is a 7-point Likert scale that the parent(s)/caregiver(s)/legally authorized representative (LAR)(s) and clinician uses to rate the change in overall seizure control, behavior, safety, and tolerability after initiation of the IP relative to Baseline (prior to treatment with the IP). It was rated as: 1- "very much improved", 2- "much improved', 3- "minimally improved", 4- "no change", 5- "minimally worse", 6- "much worse", and 7- "very much worse". Higher scores indicated worse condition.

    Measured: Baseline and at 24, 36, and 72 hours

  12. Number of hours on positive pressure ventilation attributable to the episode of SE or its treatment

    Healthcare Utilization Questionnaires include the Hospitalization Questionnaire and the Positive Pressure Ventilation (PPV) and Intubation Questionnaire. The Hospitalization Questionnaire should be collected at hospital discharge or at final study visit/contact. The need for non-invasive or invasive ventilatory support within 24 hours prior to IP initiation and following IP initiation and within 48 hours following IP discontinuation should be collected as close as possible to the event.

    Measured: Up to 4 Weeks

  13. Number of hours on positive pressure ventilation

    Measured: Up to 4 Weeks

  14. Length of stay (days) in intensive care unit (ICU)

    Measured: Up to 4 Weeks

  15. Length of stay (days) in hospital

    Measured: Up to 4 Weeks

  16. Percentage of participants requiring artificial ventilation after initiation of IP

    Measured: Up to 122 hours

  17. Percentage of participants not requiring IV anesthesia for SE treatment within 36 hours of IP initiation

    Measured: Up to 36 hours

  18. Percentage of participants not requiring IV anesthesia for SE treatment within 72 hours of IP initiation

    Measured: Up to 72 hours

  19. Percentage of participants not requiring IV anesthesia for SE treatment through the final study follow-up visit/contact

    Measured: Up to 4 Weeks

  20. Percentage of participants who do not develop super refractory status epilepticus (SRSE) through the final study follow-up visit/contact

    Measured: Up to 4 Weeks

  21. Change from Baseline in Euro Quality of Life (five-level EuroQoL five-dimensional [EQ-5D-5L]) score

    The EQ-5D-5L is the EuroQoL 5D-5L, a descriptive system that comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The participant is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the participant's health state. A positive score means quality of life improvement, a negative score, a worsening of quality of life. Higher scores indicate more problems.

    Measured: Baseline and Up to 4 Weeks

  22. Number of AEDs at discharge

    Measured: Up to 122 hours

  23. Percentage of participants requiring supplemental oxygen after initiation of IP

    Measured: Up to 4 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Apr 2023
  2. Study startMar 2024 (estimated)
  3. Primary completionAug 2024 (estimated)
  4. Study completionAug 2024 (estimated)

Why it stopped: Business reasons

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05814523
Sponsor's protocol ID
1042-SE-3004
Status last verified
May 2024
First submitted
3 Apr 2023
Last updated
14 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ganaxolone in people with Refractory Status Epilepticus, run by Marinus Pharmaceuticals at 52 sites in 16 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 14 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 52 sites in Poland, Austria, France, Germany, Israel and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of participants who will report cessation of SE within 30 minutes of investigational product (IP) initiation of at least 30 minutes duration (time frame: Up to 30 minutes). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05814523.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2024.

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