NCT05814523
Withdrawn
Phase 3
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
ConditionsRefractory Status Epilepticus
Overview
- Phase
- Phase 3
- Intervention
- Ganaxolone
- Conditions
- Refractory Status Epilepticus
- Sponsor
- Marinus Pharmaceuticals
- Locations
- 52
- Primary Endpoint
- Percentage of participants who will report cessation of SE within 30 minutes of investigational product (IP) initiation of at least 30 minutes duration
- Status
- Withdrawn
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
Ganaxolone IV solution + SOC IV AED
Intervention: Ganaxolone
Ganaxolone IV solution + SOC IV AED
Intervention: Standard of care
Placebo IV solution + SOC IV AED
Intervention: Placebo
Placebo IV solution + SOC IV AED
Intervention: Standard of care
Outcomes
Primary Outcomes
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
Status epilepticus cessation will be determined by the investigator based on clinical and electroencephalography (EEG) features
Percentage of participants who will report no escalation of treatment for persistent or recurrent SE within 36 hours of IP initiation
Time Frame: Up to 36 hours
Secondary Outcomes
- Time to SE cessation(Up to 72 hours)
- Percentage of participants reporting no escalation of treatment for persistent or recurrent SE within 36 hours of IP initiation(Up to 36 hours)
- Change from Baseline in level of sedation/ agitation as assessed by Richmond Agitation and Sedation Scale (RASS)(Baseline and at 24, 36 and 72 hours)
- Change from Baseline in Modified Rankin Scale (mRS) at the time of hospital discharge(Baseline and Up to Day 31)
- Percentage of participants with mRS > 3 at the time of hospital discharge(Up to 122 hours)
- Percentage of participants requiring artificial ventilation after initiation of IP(Up to 122 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)
- Change from Baseline in level of responsiveness as assessed by the Full Outline of UnResponsiveness (FOUR) Score scale(Baseline and at 24, 36 and 72 hours)
- Length of stay (days) in hospital(Up to 4 Weeks)
- Change from Baseline in Euro Quality of Life (five-level EuroQoL five-dimensional [EQ-5D-5L]) score(Baseline and Up to 4 Weeks)
- 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 reporting no escalation of treatment for persistent or recurrent SE within 72 hours of IP initiation(Up to 72 hours)
- Number of hours on positive pressure ventilation attributable to the episode of SE or its treatment(Up to 4 Weeks)
- Length of stay (days) in intensive care unit (ICU)(Up to 4 Weeks)
- Percentage of participants not requiring IV anesthesia for SE treatment within 72 hours of IP initiation(Up to 72 hours)
- Percentage of participants not requiring IV anesthesia for SE treatment through the final study follow-up visit/contact(Up to 4 Weeks)
- Percentage of participants who do not develop super refractory status epilepticus (SRSE) through the final study follow-up visit/contact(Up to 4 Weeks)
- Number of AEDs at discharge(Up to 122 hours)
- 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)
- Change from Baseline in Clinical Global Impression-Improvement (CGI-I) following IP initiation and at hospital discharge(Baseline and at 24, 36, and 72 hours)
- Number of hours on positive pressure ventilation(Up to 4 Weeks)
- Percentage of participants not requiring IV anesthesia for SE treatment within 36 hours of IP initiation(Up to 36 hours)
- Percentage of participants requiring supplemental oxygen after initiation of IP(Up to 4 Weeks)
Study Sites (52)
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