Study of Adjunctive Ganaxolone Treatment in Children and Young Adults With CDKL5 Deficiency Disorder

Phase 3

Completed

• Conditions: CDKL5 Deficiency Disorder
• Interventions: Drug: ganaxolone; Drug: Placebo

• Registration Number: NCT03572933
• Lead Sponsor: Marinus Pharmaceuticals

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.

Study Timeline

• Study First Submitted: 2018-06-19
• Study First Submitted QC: 2018-06-19
• Study First Posted: 2018-06-28
• Study Start: 2018-06-30
• Primary Completion: 2020-07-31
• Study Completion: 2021-05-28
• Results First Submitted: 2022-04-01
• Results First Submitted QC: 2022-06-30
• Results First Posted: 2022-07-26
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-12
• Last Update Posted: 2023-04-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 101

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ganaxolone	ganaxolone	ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks
Placebo	Placebo	placebo suspension 3x's /day for 17 weeks

Primary Outcome Measures

Name	Time	Method
Summary of 28-day Seizure Frequency for Major Motor Seizure Types	End of the double-blind 17 week treatment period	Summary of 28-day seizure frequency for Major Motor Seizure Types during the double-blind treatment period relative to the 6-week prospective baseline period; Note: Summaries are based on the sum of the individual seizures, the countable seizures, and the clusters with uncountable seizures (each cluster with uncountable seizures counts as 1 seizure). Within the baseline and post baseline intervals, 28-day seizure frequency was calculated as the total number of seizures in the interval divided by the number of days with available seizure data in the interval, multiplied by 28.

Secondary Outcome Measures

Name	Time	Method
Caregiver Global Impression of Change in Attention	End of the double-blind 17 week treatment period	Caregiver global impression of change in attention during the double-blind treatment period of ganaxolone compared to placebo. Investigators and caregivers reported improvements in attention, mood, behavior and sleep via investigator narratives
Caregiver Global Impression of Change in Target Behavior	End of the double-blind 17 week treatment period	Caregiver global impression of change in target behavior during the double-blind treatment period of ganaxolone compared to placebo. Investigators and caregivers reported improvements in attention, mood, behavior and sleep via investigator narratives.
Clinical Global Impression of Improvement - Clinician	[Time Frame: End of the double-blind 17 week treatment period]	Clinical global impression of improvement during the double-blind treatment period of ganaxolone compared to placebo
Clinical Global Impression of Improvement - Parent/Caregiver	End of the double-blind 17 week treatment period	Clinical global impression of improvement during the double-blind treatment period of ganaxolone compared to placebo. The CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses.
Percentage of Seizure-free Days for Major Motor Seizure Types	End of the double-blind 17 week treatment period	Percentage of Seizure-free Days for Major Motor Seizure types during the double-blind treatment period of ganaxolone compared to placebo. The major motor seizure types include bilateral tonic (sustained motor activity = 3 seconds), generalized tonic-clonic, atonic/drop, bilateral clonic, and focal to bilateral tonic-clonic.
Arithmetic Change in Longest Seizure Free Interval, Based on Primary Seizure Types	End of the double-blind 17 week treatment period	Arithmetic change in longest seizure free interval, based on primary seizure types during the double-blind treatment period of ganaxolone compared to placebo
Caregiver Global Impression of Change in Seizure Intensity and Duration	End of the double-blind 17 week treatment period	Caregiver global impression of change in seizure intensity and duration during the double-blind treatment period of ganaxolone compared to placebo. CGI-C is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention.

Trial Locations

Locations (2)

Marinus Research Site; 🇬🇧 London, United Kingdom

Marinus Research Facility; 🇬🇧 Glasgow, United Kingdom