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NCT Number: NCT03572933

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

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.

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Key information

Conditions

CDKL5 Deficiency Disorder Brain Diseases Central Nervous System Diseases Epilepsy Nervous System Diseases Neurologic Manifestations Pathological Conditions, Signs and Symptoms Seizures Signs and Symptoms

Age range

2 year–21 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Marinus Research Site, Brisbane, Queensland, Australia

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Ganaxolone

Drug

active drug

Placebo

Drug

inactive

Other names: Placebo (for ganaxolone)

Primary outcomes

  1. Summary of 28-day Seizure Frequency for Major Motor Seizure Types

    Time frame: 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 outcomes

  1. Caregiver Global Impression of Change in Attention

    Time frame: 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

  2. Caregiver Global Impression of Change in Target Behavior

    Time frame: 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.

  3. Clinical Global Impression of Improvement - Parent/Caregiver

    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. The CGI is rated on a 7-point scale, with the severity of illness scale using a range of responses.

  4. Clinical Global Impression of Improvement - Clinician

    Time frame: [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

  5. Percentage of Seizure-free Days for Major Motor Seizure Types

    Time frame: 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.

  6. Arithmetic Change in Longest Seizure Free Interval, Based on Primary Seizure Types

    Time frame: 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

  7. Caregiver Global Impression of Change in Seizure Intensity and Duration

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Marinus Pharmaceuticals

Industry

Registry information

Official study 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

Acronym: Marigold

Important dates

Study start
2018
Primary completion
2020
Study completion
2021
First posted
Jun 28, 2018
Registry last updated
Apr 14, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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