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

NCT03572933 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 1042-CDD-30012018-001180-23
• Study Type: interventional
• Target: 101
• Locations: 8 countries
• Sites: 36

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.

Conditions

CDKL5 Deficiency Disorder

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Caregiver Global Impression of Change in Attention

  End of the double-blind 17 week treatment period

• Caregiver Global Impression of Change in Target Behavior

  End of the double-blind 17 week treatment period

• Clinical Global Impression of Improvement - Parent/Caregiver

  End of the double-blind 17 week treatment period

• Clinical Global Impression of Improvement - Clinician

  [Time Frame: End of the double-blind 17 week treatment period]

• Percentage of Seizure-free Days for Major Motor Seizure Types

  End of the double-blind 17 week treatment period

Study Arms (2)

Ganaxolone

EXPERIMENTAL

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

Drug: ganaxolone

Placebo

PLACEBO COMPARATOR

placebo suspension 3x's /day for 17 weeks

Drug: Placebo

Interventions

ganaxolone DRUG

active drug

Ganaxolone

Placebo DRUG

inactive

Also known as: Placebo (for ganaxolone)

Placebo

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Marinus Pharmaceuticals: lead

Study Sites (36)

Marinus Research Site

Phoenix, Arizona, 85016, United States

Location

Marinus Research Site

Los Angeles, California, 90095-1742, United States

Location

Marinus Research Site

Aurora, Colorado, 80045, United States

Location

Marinus Research Site

Gulf Breeze, Florida, 32561, United States

Location

Marinus Research Site

Orlando, Florida, 32819, United States

Location

Marinus Research Site

Norcross, Georgia, 30093, United States

Location

Marinus Research Site

Chicago, Illinois, 60612-3852, United States

Location

Marinus Research Site

Iowa City, Iowa, 52242, United States

Location

Marinus Research Site

Boston, Massachusetts, 02115, United States

Location

Marinus Research Site

Rochester, Minnesota, 55905, United States

Location

Marinus Research Site

St Louis, Missouri, 63130, United States

Location

Marinus Research Site

Livingston, New Jersey, 07039, United States

Location

Marinus Research Site

Cleveland, Ohio, 44195, United States

Location

Marinus Research Site

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Marinus Research Site

Pittsburgh, Pennsylvania, 15224, United States

Location

Marinus Research Site

Fort Worth, Texas, 76104, United States

Location

Marinus Research Site

Houston, Texas, 77030, United States

Location

Marinus Research Site

Brisbane, Queensland, 4101, Australia

Location

Marinus Research Site

Heidelberg, Victoria, 3084, Australia

Location

Marinus Research Site

Melbourne, Victoria, 3168, Australia

Location

Marinus Research Site

Paris, France

Location

Marinus Research Site

Ramat Gan, Israel

Location

Marinus Research Site

Florence, Italy

Location

Marinus Research Site

Milan, Italy

Location

Marinus Research Site

Pavia, Italy

Location

Marinus Research Site

Roma, Italy

Location

Marinus Research Site

Verona, Italy

Location

Marinus Research Site

Bydgoszcz, Poland

Location

Marinus Research Site

Krakow, Poland

Location

Marinus Research Site

Moscow, Russia

Location

Marinus Research Site

Nizhny Novgorod, Russia

Location

Marinus Research Site

Novosibirsk, Russia

Location

Marinus Research Site

Birmingham, United Kingdom

Location

Marinus Research Site

Bristol, United Kingdom

Location

Marinus Research Facility

Glasgow, United Kingdom

Location

Marinus Research Site

London, United Kingdom

Location

Related Publications (2)

• Yasmen N, Sluter MN, Yu Y, Jiang J. Ganaxolone for management of seizures associated with CDKL5 deficiency disorder. Trends Pharmacol Sci. 2023 Feb;44(2):128-129. doi: 10.1016/j.tips.2022.11.007. Epub 2022 Dec 12. No abstract available.

  PMID: 36517284 DERIVED

• Knight EMP, Amin S, Bahi-Buisson N, Benke TA, Cross JH, Demarest ST, Olson HE, Specchio N, Fleming TR, Aimetti AA, Gasior M, Devinsky O; Marigold Trial Group. Safety and efficacy of ganaxolone in patients with CDKL5 deficiency disorder: results from the double-blind phase of a randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2022 May;21(5):417-427. doi: 10.1016/S1474-4422(22)00077-1.

  PMID: 35429480 DERIVED

MeSH Terms

Conditions

CDKL5 deficiency disorder; Seizures; Epilepsy

Interventions

ganaxolone

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases

Results Point of Contact

• Title: Marinus Clinical Trials Submission Manager
• Organization: Marinus Pharmaceuticals, Inc.

clinicaltrials@marinuspharma.com

484-801-4670

Study Officials

• Joseph Hulihan, MD

  Marinus Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The double-blind phase will randomize subjects to adjunctive ganaxolone or placebo at a 1:1 ratio to standard of care

Study Record Dates

• First Submitted: June 19, 2018
• First Posted: June 28, 2018
• Study Start: June 30, 2018
• Primary Completion: July 31, 2020
• Study Completion: May 28, 2021
• Last Updated: April 14, 2023
• Results First Posted: July 26, 2022

Record last verified: 2023-04

Locations

GB (4); PL (2); IL (1); AU (3); FR (1); RU (3); IT (5); US (17)