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

CDKL5 Deficiency Disorder Clinical Trial

— Marigold  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03572933
• Other study ID #: 1042-CDD-3001
• Secondary ID: 2018-001180-23
• Status: Completed
• Phase: Phase 3
• Start date: June 30, 2018
• Est. completion date: May 28, 2021

Study information

• Verified date: April 2023
• Source: Marinus Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: May 28, 2021
• Est. primary completion date: July 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• CDKL5 Deficiency Disorder
• Disease

Intervention

Drug:
• ganaxolone
active drug
• Placebo
inactive

Locations

Country	Name	City	State
Australia	Marinus Research Site	Brisbane	Queensland
Australia	Marinus Research Site	Heidelberg	Victoria
Australia	Marinus Research Site	Melbourne	Victoria
France	Marinus Research Site	Paris
Israel	Marinus Research Site	Ramat Gan
Italy	Marinus Research Site	Firenze
Italy	Marinus Research Site	Milano
Italy	Marinus Research Site	Pavia
Italy	Marinus Research Site	Roma
Italy	Marinus Research Site	Verona
Poland	Marinus Research Site	Bydgoszcz
Poland	Marinus Research Site	Kraków
Russian Federation	Marinus Research Site	Moscow
Russian Federation	Marinus Research Site	Nizhniy Novgorod
Russian Federation	Marinus Research Site	Novosibirsk
United Kingdom	Marinus Research Site	Birmingham
United Kingdom	Marinus Research Site	Bristol
United Kingdom	Marinus Research Facility	Glasgow
United Kingdom	Marinus Research Site	London
United States	Marinus Research Site	Aurora	Colorado
United States	Marinus Research Site	Boston	Massachusetts
United States	Marinus Research Site	Chicago	Illinois
United States	Marinus Research Site	Cleveland	Ohio
United States	Marinus Research Site	Fort Worth	Texas
United States	Marinus Research Site	Gulf Breeze	Florida
United States	Marinus Research Site	Houston	Texas
United States	Marinus Research Site	Iowa City	Iowa
United States	Marinus Research Site	Livingston	New Jersey
United States	Marinus Research Site	Los Angeles	California
United States	Marinus Research Site	Norcross	Georgia
United States	Marinus Research Site	Orlando	Florida
United States	Marinus Research Site	Philadelphia	Pennsylvania
United States	Marinus Research Site	Phoenix	Arizona
United States	Marinus Research Site	Pittsburgh	Pennsylvania
United States	Marinus Research Site	Rochester	Minnesota
United States	Marinus Research Site	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Marinus Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  France,  Israel,  Italy,  Poland,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Summary of 28-day Seizure Frequency for Major Motor Seizure Types	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.	End of the double-blind 17 week treatment period
Secondary	Caregiver Global Impression of Change in Attention	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	End of the double-blind 17 week treatment period
Secondary	Caregiver Global Impression of Change in Target Behavior	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.	End of the double-blind 17 week treatment period
Secondary	Clinical Global Impression of Improvement - Parent/Caregiver	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.	End of the double-blind 17 week treatment period
Secondary	Clinical Global Impression of Improvement - Clinician	Clinical global impression of improvement during the double-blind treatment period of ganaxolone compared to placebo	[Time Frame: End of the double-blind 17 week treatment period]
Secondary	Percentage of Seizure-free Days for Major Motor Seizure Types	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.	End of the double-blind 17 week treatment period
Secondary	Arithmetic Change in Longest Seizure Free Interval, Based on Primary Seizure Types	Arithmetic change in longest seizure free interval, based on primary seizure types during the double-blind treatment period of ganaxolone compared to placebo	End of the double-blind 17 week treatment period
Secondary	Caregiver Global Impression of Change in Seizure Intensity and Duration	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.	End of the double-blind 17 week treatment period