Clinical trial NCT03572933: Study of Adjunctive Ganaxolone Treatment in Children and Young Adults With CDKL5 Deficiency Disorder
Official title: A Double-blind, Randomized, Placebo-controlled Trial of Adjunctive Ganaxolone Treatment in Children and Young Adults With Cyclin-dependent Kinase-like 5 (CDKL5) Deficiency Disorder (CDD) Followed by Long-term Open-label Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: CDKL5 Deficiency Disorder
Keywords: refractory seizures
genetic pediatric encephalopathies
epilepsy in children
seizure disorder
Lead sponsor: Marinus Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-06-28
Enrollment: 101
Sex: ALL
Minimum age (years): 2
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The double-blind phase will randomize subjects to adjunctive ganaxolone or placebo at a 1:1 ratio to standard of care
Primary purpose: TREATMENT

Brief summary: A clinical study to evaluate the efficacy, safety, and tolerability of adjunctive ganaxolone therapy compared to placebo for the treatment of seizures in children and young adults with genetically confirmed CDKL5 gene mutation.

Detailed description: The Marigold Study is a global, double-blind, placebo-controlled, Phase 3 clinical trial that will enroll approximately 70 patients between the ages of 2 and 21 with a confirmed disease-related CDKL5 gene variant. Patients will undergo a baseline period before being randomized to receive, in addition to their existing anti-seizure treatment, either ganaxolone or placebo for 17 weeks. Following the treatment period, all patients that meet certain eligibility requirements will have the opportunity to receive ganaxolone in the open label phase of the study. The study's primary efficacy endpoint is percent reduction in seizures. Secondary outcome measures will include non-seizure-related endpoints to capture certain behavioral and sleep disturbances that have been seen in previous clinical studies with ganaxolone.

Eligibility criteria: Inclusion Criteria:

* Genetically confirmed CDKL5 gene mutation, seizure onset by 1 year of age and lack of independent ambulation by 2 years of age
* Failure to control seizures despite 2 or more anti-seizure medications
* At least 16 seizures per 28 days of primary seizure types
* On a stable regimen of 0-4 anti-seizure medications (Vagus nerve stimulator, ketogenic diet, and modified Atkins diet do not count towards this limit)
* Additional Inclusion Criteria apply and can be discussed with study team

Exclusion Criteria:

* Previous exposure to ganaxolone
* West Syndrome with hypsarrhythmia pattern on EEG or seizures predominantly of Infantile Spasms type
* Use of adrenocorticotropic hormone (ACTH), prednisone or other glucocorticoid or use of moderate or strong inducers or inhibitors of CYP3A4/5/7 are prohibited
* Use of tetrahydrocannabinol (THC) or cannabidiol (CBD) is prohibited during the double-blind phase, unless patient has a prescription of Epidiolex®
* Exposure to any other investigational drug within 30 days or fewer than 5 half-lives prior to screening
* Plasma allopregnanolone-sulfate (Allo-S) levels greater than or equal to 6.0 ng/ml at screening visit
* Additional Exclusion Criteria apply and can be discussed with study team

Primary outcomes:
measure: Summary of 28-day Seizure Frequency for Major Motor Seizure Types
timeFrame: End of the double-blind 17 week treatment period
Secondary outcomes:
measure: Caregiver Global Impression of Change in Attention
timeFrame: End of the double-blind 17 week treatment period
measure: Caregiver Global Impression of Change in Target Behavior
timeFrame: End of the double-blind 17 week treatment period
measure: Clinical Global Impression of Improvement - Parent/Caregiver
timeFrame: End of the double-blind 17 week treatment period
measure: Clinical Global Impression of Improvement - Clinician
timeFrame: [Time Frame: End of the double-blind 17 week treatment period]
measure: Percentage of Seizure-free Days for Major Motor Seizure Types
timeFrame: End of the double-blind 17 week treatment period
measure: Arithmetic Change in Longest Seizure Free Interval, Based on Primary Seizure Types
timeFrame: End of the double-blind 17 week treatment period
measure: Caregiver Global Impression of Change in Seizure Intensity and Duration
timeFrame: End of the double-blind 17 week treatment period
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Marinus Research Site
state: Arizona
city: Los Angeles
country: United States
facility: Marinus Research Site
state: California
city: Aurora
country: United States
facility: Marinus Research Site
state: Colorado
city: Gulf Breeze
country: United States
facility: Marinus Research Site
state: Florida
city: Orlando
country: United States
facility: Marinus Research Site
state: Florida
city: Norcross
country: United States
facility: Marinus Research Site
state: Georgia
city: Chicago
country: United States
facility: Marinus Research Site
state: Illinois
city: Iowa City
country: United States
facility: Marinus Research Site
state: Iowa
city: Boston
country: United States
facility: Marinus Research Site
state: Massachusetts
city: Rochester
country: United States
facility: Marinus Research Site
state: Minnesota
city: Saint Louis
country: United States
facility: Marinus Research Site
state: Missouri
city: Livingston
country: United States
facility: Marinus Research Site
state: New Jersey
city: Cleveland
country: United States
facility: Marinus Research Site
state: Ohio
city: Philadelphia
country: United States
facility: Marinus Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Marinus Research Site
state: Pennsylvania
city: Fort Worth
country: United States
facility: Marinus Research Site
state: Texas
city: Houston
country: United States
facility: Marinus Research Site
state: Texas
city: Brisbane
country: Australia
facility: Marinus Research Site
state: Queensland
city: Heidelberg
country: Australia
facility: Marinus Research Site
state: Victoria
city: Melbourne
country: Australia
facility: Marinus Research Site
state: Victoria
city: Paris
country: France
facility: Marinus Research Site
city: Ramat Gan
country: Israel
facility: Marinus Research Site
city: Firenze
country: Italy
facility: Marinus Research Site
city: Milano
country: Italy
facility: Marinus Research Site
city: Pavia
country: Italy
facility: Marinus Research Site
city: Roma
country: Italy
facility: Marinus Research Site
city: Verona
country: Italy
facility: Marinus Research Site
city: Bydgoszcz
country: Poland
facility: Marinus Research Site
city: Kraków
country: Poland
facility: Marinus Research Site
city: Moscow
country: Russian Federation
facility: Marinus Research Site
city: Nizhniy Novgorod
country: Russian Federation
facility: Marinus Research Site
city: Novosibirsk
country: Russian Federation
facility: Marinus Research Site
city: Birmingham
country: United Kingdom
facility: Marinus Research Site
city: Bristol
country: United Kingdom
facility: Marinus Research Site
city: Glasgow
country: United Kingdom
facility: Marinus Research Facility
city: London
country: United Kingdom
facility: Marinus Research Site
Study officials:
affiliation: Marinus Pharmaceuticals, Inc.
name: Joseph Hulihan, MD
role: STUDY_DIRECTOR
References:
citation: Knight EMP, Amin S, Bahi-Buisson N, Benke TA, Cross JH, Demarest ST, Olson HE, Specchio N, Fleming TR, Aimetti AA, Gasior M, Devinsky O; Marigold Trial Group. Safety and efficacy of ganaxolone in patients with CDKL5 deficiency disorder: results from the double-blind phase of a randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2022 May;21(5):417-427. doi: 10.1016/S1474-4422(22)00077-1.