CDKL5 Deficiency DisorderPhase 3MarigoldNCT03572933
Study of Adjunctive Ganaxolone Treatment in Children and Young Adults With CDKL5 Deficiency Disorder
A Phase 3 study testing ganaxolone in people with CDKL5 Deficiency Disorder, run by Marinus Pharmaceuticals at 36 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 21 years
- Conditions the study is for
- CDKL5 Deficiency Disorder
- What is being tested?
- ganaxolone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 101 participants
- Where
- 36 sitesin 8 countries
- Study dates
- 30 Jun 2018to 28 May 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
36 sites in 8 countries.
36 sites in 8 countries
United States17 sites
Marinus Research Site
Aurora, Colorado, 80045
Marinus Research Site
Boston, Massachusetts, 02115
Marinus Research Site
Chicago, Illinois, 60612-3852
Marinus Research Site
Cleveland, Ohio, 44195
Marinus Research Site
Fort Worth, Texas, 76104
Marinus Research Site
Gulf Breeze, Florida, 32561
Marinus Research Site
Houston, Texas, 77030
Marinus Research Site
Iowa City, Iowa, 52242
Marinus Research Site
Livingston, New Jersey, 07039
Marinus Research Site
Los Angeles, California, 90095-1742
Marinus Research Site
Norcross, Georgia, 30093
Marinus Research Site
Orlando, Florida, 32819
Marinus Research Site
Philadelphia, Pennsylvania, 19104-4318
Marinus Research Site
Phoenix, Arizona, 85016
Marinus Research Site
Pittsburgh, Pennsylvania, 15224
Marinus Research Site
Rochester, Minnesota, 55905
Marinus Research Site
St Louis, Missouri, 63130
Italy5 sites
Marinus Research Site
Florence
Marinus Research Site
Milan
Marinus Research Site
Pavia
Marinus Research Site
Roma
Marinus Research Site
Verona
United Kingdom4 sites
Marinus Research Site
Birmingham
Marinus Research Site
Bristol
Marinus Research Facility
Glasgow
Marinus Research Site
London
Australia3 sites
Marinus Research Site
Brisbane, Queensland, 4101
Marinus Research Site
Heidelberg, Victoria, 3084
Marinus Research Site
Melbourne, Victoria, 3168
Russia3 sites
Marinus Research Site
Moscow
Marinus Research Site
Nizhny Novgorod
Marinus Research Site
Novosibirsk
About this study
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
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.
Read the 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.
- Conditions
- CDKL5 Deficiency Disorder
- Being tested
- ganaxolone, Placebo
- Keywords
- refractory seizures, genetic pediatric encephalopathies, epilepsy in children, seizure disorder
- Medical subject headings
- CDKL5 deficiency disorder, Seizures, Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ganaxoloneDrug
active drug
PlaceboDrug
Also called Placebo (for ganaxolone)
inactive
| Study group | Role | What they receive |
|---|---|---|
| Ganaxolone | Experimental | ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks Receives: Drug: ganaxolone |
| Placebo | Placebo comparator | placebo suspension 3x's /day for 17 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: End of the double-blind 17 week treatment period
Secondary outcomes (7)
Caregiver Global Impression of Change in Attention
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
Measured: End of the double-blind 17 week treatment period
Caregiver Global Impression of Change in Target Behavior
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.
Measured: End of the double-blind 17 week treatment period
Clinical Global Impression of Improvement - Parent/Caregiver
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.
Measured: End of the double-blind 17 week treatment period
Clinical Global Impression of Improvement - Clinician
Clinical global impression of improvement during the double-blind treatment period of ganaxolone compared to placebo
Measured: [Time Frame: End of the double-blind 17 week treatment period]
Percentage of Seizure-free Days for Major Motor Seizure Types
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.
Measured: End of the double-blind 17 week treatment period
Arithmetic Change in Longest Seizure Free Interval, Based on Primary Seizure Types
Arithmetic change in longest seizure free interval, based on primary seizure types during the double-blind treatment period of ganaxolone compared to placebo
Measured: End of the double-blind 17 week treatment period
Caregiver Global Impression of Change in Seizure Intensity and Duration
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.
Measured: End of the double-blind 17 week treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2018
- Study start30 Jun 2018
- Primary completion31 Jul 2020
- Study completion28 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for CDKL5 Deficiency DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 101 participants (actual)
Sponsor and investigators
- Lead sponsor
- Marinus Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Joseph Hulihan, MD, Study director, Marinus Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03572933
- Sponsor's protocol ID
- 1042-CDD-3001
- Other IDs
- 2018-001180-23, 2018
- Acronym
- Marigold
- Status last verified
- Apr 2023
- First submitted
- 19 Jun 2018
- Last updated
- 14 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 36517284Knight 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.
PubMed 35429480
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03572933
- Acronym / sponsor ID
- Marigold / 1042-CDD-3001
- Conditions
- CDKL5 Deficiency Disorder
- Keywords
- refractory seizures, genetic pediatric encephalopathies, epilepsy in children, seizure disorder
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 101 participants (actual)
- Lead sponsor
- Marinus PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 30 Jun 2018 (actual)
- Primary completion
- 31 Jul 2020 (actual)
- Study completion
- 28 May 2021 (actual)
- First posted
- 28 Jun 2018 (actual)
- Results
- Posted 26 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- The double-blind phase will randomize subjects to adjunctive ganaxolone or placebo at a 1:1 ratio to standard of care
| Arm | Type | Receives |
|---|---|---|
| Ganaxolone | Experimental | Drug: ganaxoloneganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks |
| Placebo | Placebo comparator | Drug: Placeboplacebo suspension 3x's /day for 17 weeks |
Who may qualify
- Ages
- 2 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ganaxoloneactive drug | Drug | Ganaxolone |
| PlaceboAlso: Placebo (for ganaxolone)inactive | Drug | Placebo |
Primary outcome
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.
7 secondary outcomes
Caregiver Global Impression of Change in Attention
Time frame: End of the double-blind 17 week treatment period
Caregiver Global Impression of Change in Target Behavior
Time frame: End of the double-blind 17 week treatment period
Clinical Global Impression of Improvement - Parent/Caregiver
Time frame: End of the double-blind 17 week treatment period
Clinical Global Impression of Improvement - Clinician
Time frame: [Time Frame: End of the double-blind 17 week treatment period]
Percentage of Seizure-free Days for Major Motor 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
Time frame: End of the double-blind 17 week treatment period
Caregiver Global Impression of Change in Seizure Intensity and Duration
Time frame: End of the double-blind 17 week treatment period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36517284Yasmen 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.
- Derived from this study: PubMed 35429480Knight 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.
Related trials for CDKL5 Deficiency Disorder
Not yet recruitingPhase 3
Open-label, Single-arm Trial of Ganaxolone in CDD Patients 6 Months to Less Than 2 Years Old
CDKL5 Deficiency Disorder
Active, not recruitingObservational study
Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome
Not yet recruiting
Efficacy and Safety of Daily Home-based Hyperthermic Baths for Reducing Epileptic Seizures in CDKL5 Deficiency Disorder: A PROBE Clinical Trial
CDKL5 Deficiency Disorder
Active, not recruitingPhase 3
A Phase 3 Study to Examine the Efficacy and Safety of ZX008 in Subjects With CDKL5 Deficiency Disorder.
CDKL5 Deficiency Disorder, Generalized Tonic Clonic Seizure
RecruitingObservational study
A Retrospective Survey-based Multicenter Study to Delineate the Molecular and Phenotypic Spectrum of Epilepsy-dyskinesia Syndromes
Epilepsy in Children, Dyskinesias
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph Hulihan, MD study director
Marinus Pharmaceuticals, Inc.
36 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ganaxolone in people with CDKL5 Deficiency Disorder, run by Marinus Pharmaceuticals at 36 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in United States, Italy, United Kingdom, Australia, Russia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Summary of 28-day Seizure Frequency for Major Motor Seizure Types (time frame: End of the double-blind 17 week treatment period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03572933, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2023.