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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03572933




Registration number
NCT03572933
Ethics application status
Date submitted
19/06/2018
Date registered
28/06/2018
Date last updated
14/04/2023

Titles & IDs
Public title
Study of Adjunctive Ganaxolone Treatment in Children and Young Adults With CDKL5 Deficiency Disorder
Scientific 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
Secondary ID [1] 0 0
2018-001180-23
Secondary ID [2] 0 0
1042-CDD-3001
Universal Trial Number (UTN)
Trial acronym
Marigold
Linked study record

Health condition
Health condition(s) or problem(s) studied:
CDKL5 Deficiency Disorder 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ganaxolone
Treatment: Drugs - Placebo

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

Placebo comparator: Placebo - placebo suspension 3x's /day for 17 weeks


Treatment: Drugs: ganaxolone
active drug

Treatment: Drugs: Placebo
inactive
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Summary of 28-day Seizure Frequency for Major Motor Seizure Types
Timepoint [1] 0 0
End of the double-blind 17 week treatment period
Secondary outcome [1] 0 0
Caregiver Global Impression of Change in Attention
Timepoint [1] 0 0
End of the double-blind 17 week treatment period
Secondary outcome [2] 0 0
Caregiver Global Impression of Change in Target Behavior
Timepoint [2] 0 0
End of the double-blind 17 week treatment period
Secondary outcome [3] 0 0
Clinical Global Impression of Improvement - Parent/Caregiver
Timepoint [3] 0 0
End of the double-blind 17 week treatment period
Secondary outcome [4] 0 0
Clinical Global Impression of Improvement - Clinician
Timepoint [4] 0 0
[Time Frame: End of the double-blind 17 week treatment period]
Secondary outcome [5] 0 0
Percentage of Seizure-free Days for Major Motor Seizure Types
Timepoint [5] 0 0
End of the double-blind 17 week treatment period
Secondary outcome [6] 0 0
Arithmetic Change in Longest Seizure Free Interval, Based on Primary Seizure Types
Timepoint [6] 0 0
End of the double-blind 17 week treatment period
Secondary outcome [7] 0 0
Caregiver Global Impression of Change in Seizure Intensity and Duration
Timepoint [7] 0 0
End of the double-blind 17 week treatment period

Eligibility
Key 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
Minimum age
2 Years
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/06/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/05/2021
Sample size
Target
Accrual to date
Final
101
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Marinus Research Site - Brisbane
Recruitment hospital [2] 0 0
Marinus Research Site - Heidelberg
Recruitment hospital [3] 0 0
Marinus Research Site - Melbourne
Recruitment postcode(s) [1] 0 0
4101 - Brisbane
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
3168 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Iowa
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
Ohio
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Texas
Country [15] 0 0
France
State/province [15] 0 0
Paris
Country [16] 0 0
Israel
State/province [16] 0 0
Ramat Gan
Country [17] 0 0
Italy
State/province [17] 0 0
Firenze
Country [18] 0 0
Italy
State/province [18] 0 0
Milano
Country [19] 0 0
Italy
State/province [19] 0 0
Pavia
Country [20] 0 0
Italy
State/province [20] 0 0
Roma
Country [21] 0 0
Italy
State/province [21] 0 0
Verona
Country [22] 0 0
Poland
State/province [22] 0 0
Bydgoszcz
Country [23] 0 0
Poland
State/province [23] 0 0
Kraków
Country [24] 0 0
Russian Federation
State/province [24] 0 0
Moscow
Country [25] 0 0
Russian Federation
State/province [25] 0 0
Nizhniy Novgorod
Country [26] 0 0
Russian Federation
State/province [26] 0 0
Novosibirsk
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Birmingham
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Bristol
Country [29] 0 0
United Kingdom
State/province [29] 0 0
Glasgow
Country [30] 0 0
United Kingdom
State/province [30] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Marinus Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT03572933
Trial related presentations / publications
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. Erratum In: Lancet Neurol. 2022 Jul;21(7):e7. doi: 10.1016/S1474-4422(22)00230-7.
Public notes

Contacts
Principal investigator
Name 0 0
Joseph Hulihan, MD
Address 0 0
Marinus Pharmaceuticals, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03572933