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

Marinus Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: CDKL5 Deficiency Disorder

Treatments: Drug: Placebo; Drug: ganaxolone

Study type: Interventional

Funder types: Industry

Identifiers

NCT03572933

2018-001180-23 (EudraCT Number)

1042-CDD-3001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 101 patients

Sex: All

Ages: 2 to 21 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

101 participants in 2 patient groups, including a placebo group

Ganaxolone

Experimental group

Description:

ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks

Treatment:

Drug: ganaxolone

Placebo

Placebo Comparator group

Description:

placebo suspension 3x's /day for 17 weeks

Treatment:

Drug: Placebo