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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
First received
Last updated
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
Health authority
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

Study Design


Related Conditions & MeSH terms


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
See also
  Status Clinical Trial Phase
Recruiting NCT05064878 - A Study to Investigate the Efficacy and Safety of ZX008 in Subjects With CDKL5 Deficiency Disorder Phase 3
Not yet recruiting NCT06447675 - Efficacy and Safety Evaluation of Hyperthermic Baths in the Treatment of Seizures in Children With CDKL5 Deficiency N/A
Not yet recruiting NCT05249556 - Double-blind, Randomized, Placebo-controlled Trial of Ganaxolone in CDKL5 Deficiency Patients 6 Months to Less Than 2 Years Old Phase 3
Recruiting NCT05558371 - International CDKL5 Clinical Research Network