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

• ClinicalTrials.gov Identifier: NCT03572933
• Recruitment Status: Active, not recruiting
• First Posted: June 28, 2018
• Last Update Posted: November 13, 2020
• Sponsor: Marinus Pharmaceuticals
• Information provided by (Responsible Party): Marinus Pharmaceuticals

Study Description

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.

Condition or disease	Intervention/treatment	Phase
CDKL5 Deficiency Disorder	Drug: ganaxolone; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 102 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: The double-blind phase will randomize subjects to adjunctive ganaxolone or placebo at a 1:1 ratio to standard of care
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 30, 2018
• Actual Primary Completion Date: July 31, 2020
• Estimated Study Completion Date: October 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ganaxolone; ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks	Drug: ganaxolone; active drug
Placebo Comparator: Placebo; placebo suspension 3x's /day for 17 weeks	Drug: Placebo; inactive; Other Name: Placebo (for ganaxolone)

Outcome Measures

Primary Outcome Measures :

1. Percent change in 28-day seizure frequency [ Time Frame: End of the double-blind 17 week treatment period ]
   Percent change in 28-day seizure frequency during the double-blind treatment period relative to the 6-week prospective baseline period

Secondary Outcome Measures :

1. Change in caregiver global impression of change in attention [ Time Frame: End of the double-blind 17 week treatment period ]
   Change in caregiver global impression of change in attention during the double-blind treatment period of ganaxolone compared to placebo
2. Change in caregiver global impression of change in target behavior [ Time Frame: End of the double-blind 17 week treatment period ]
   Change in caregiver global impression of change in target behavior during the double-blind treatment period of ganaxolone compared to placebo
3. Clinical Global Impression of Improvement [ 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
4. Arithmetic change in percent of seizure-free days of primary seizure types [ Time Frame: End of the double-blind 17 week treatment period ]
   Arithmetic change in percent of seizure-free days of primary seizure types during the double-blind treatment period of ganaxolone compared to placebo
5. 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
6. 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

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 21 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Arizona

Marinus Research Site

Phoenix, Arizona, United States, 85016

United States, California

Marinus Research Site

Los Angeles, California, United States, 90095-1742

United States, Colorado

Marinus Research Site

Aurora, Colorado, United States, 80045

United States, Florida

Marinus Research Site

Gulf Breeze, Florida, United States, 32561

Marinus Research Site

Orlando, Florida, United States, 32819

United States, Georgia

Marinus Research Site

Norcross, Georgia, United States, 30093

United States, Illinois

Marinus Research Site

Chicago, Illinois, United States, 60612-3852

United States, Iowa

Marinus Research Site

Iowa City, Iowa, United States, 52242

United States, Massachusetts

Marinus Research Site

Boston, Massachusetts, United States, 02115

United States, Minnesota

Marinus Research Site

Rochester, Minnesota, United States, 55905

United States, Missouri

Marinus Research Site

Saint Louis, Missouri, United States, 63130

United States, New Jersey

Marinus Research Site

Livingston, New Jersey, United States, 07039

United States, Ohio

Marinus Research Site

Cleveland, Ohio, United States, 44195

United States, Pennsylvania

Marinus Research Site

Philadelphia, Pennsylvania, United States, 19104-4318

Marinus Research Site

Pittsburgh, Pennsylvania, United States, 15224

United States, Texas

Marinus Research Site

Fort Worth, Texas, United States, 76104

Marinus Research Site

Houston, Texas, United States, 77030

Australia, Queensland

Marinus Research Site

Brisbane, Queensland, Australia, 4101

Australia, Victoria

Marinus Research Site

Heidelberg, Victoria, Australia, 3084

Marinus Research Site

Melbourne, Victoria, Australia, 3168

France

Marinus Research Site

Paris, France

Israel

Marinus Research Site

Ramat Gan, Israel

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, Italy

Poland

Marinus Research Site

Bydgoszcz, Poland

Marinus Research Site

Kraków, Poland

Russian Federation

Marinus Research Site

Moscow, Russian Federation

Marinus Research Site

Nizhniy Novgorod, Russian Federation

Marinus Research Site

Novosibirsk, Russian Federation

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 Kingdom

Sponsors and Collaborators

Marinus Pharmaceuticals

Investigators

• Study Director: Joseph Hulihan, MD; Marinus Pharmaceuticals, Inc.

More Information

• Responsible Party: Marinus Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03572933
• Other Study ID Numbers: 1042-CDD-3001; 2018-001180-23 ( EudraCT Number )
• First Posted: June 28, 2018
• Last Update Posted: November 13, 2020
• Last Verified: November 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Marinus Pharmaceuticals:

refractory seizures; genetic pediatric encephalopathies; epilepsy in children; seizure disorder

Additional relevant MeSH terms:

Disease; Pathologic Processes; Pregnanolone; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs