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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-001180-23 | EudraCT Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ganaxolone | Experimental | ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks |
|
| Placebo | Placebo Comparator | placebo suspension 3x's /day for 17 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ganaxolone | Drug | active drug |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | End of the double-blind 17 week treatment period |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Joseph Hulihan, MD | Marinus Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Marinus Research Site | Phoenix | Arizona | 85016 | United States | ||
| Marinus Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36517284 | Derived | 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. | |
| 35429480 | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | placebo suspension 3x's /day for 17 weeks Placebo: inactive |
| FG001 | Ganaxolone | ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks ganaxolone: active drug |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 2, 2020 | Apr 12, 2023 |
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The double-blind phase will randomize subjects to adjunctive ganaxolone or placebo at a 1:1 ratio to standard of care
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| Drug |
inactive |
|
|
| 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. | 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. | 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 | [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. | 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 | 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. | End of the double-blind 17 week treatment period |
| Los Angeles |
| California |
| 90095-1742 |
| United States |
| Marinus Research Site | Aurora | Colorado | 80045 | United States |
| Marinus Research Site | Gulf Breeze | Florida | 32561 | United States |
| Marinus Research Site | Orlando | Florida | 32819 | United States |
| Marinus Research Site | Norcross | Georgia | 30093 | United States |
| Marinus Research Site | Chicago | Illinois | 60612-3852 | United States |
| Marinus Research Site | Iowa City | Iowa | 52242 | United States |
| Marinus Research Site | Boston | Massachusetts | 02115 | United States |
| Marinus Research Site | Rochester | Minnesota | 55905 | United States |
| Marinus Research Site | St Louis | Missouri | 63130 | United States |
| Marinus Research Site | Livingston | New Jersey | 07039 | United States |
| Marinus Research Site | Cleveland | Ohio | 44195 | United States |
| Marinus Research Site | Philadelphia | Pennsylvania | 19104-4318 | United States |
| Marinus Research Site | Pittsburgh | Pennsylvania | 15224 | United States |
| Marinus Research Site | Fort Worth | Texas | 76104 | United States |
| Marinus Research Site | Houston | Texas | 77030 | United States |
| Marinus Research Site | Brisbane | Queensland | 4101 | Australia |
| Marinus Research Site | Heidelberg | Victoria | 3084 | Australia |
| Marinus Research Site | Melbourne | Victoria | 3168 | Australia |
| Marinus Research Site | Paris | France |
| Marinus Research Site | Ramat Gan | Israel |
| Marinus Research Site | Florence | Italy |
| Marinus Research Site | Milan | Italy |
| Marinus Research Site | Pavia | Italy |
| Marinus Research Site | Roma | Italy |
| Marinus Research Site | Verona | Italy |
| Marinus Research Site | Bydgoszcz | Poland |
| Marinus Research Site | Krakow | Poland |
| Marinus Research Site | Moscow | Russia |
| Marinus Research Site | Nizhny Novgorod | Russia |
| Marinus Research Site | Novosibirsk | Russia |
| Marinus Research Site | Birmingham | United Kingdom |
| Marinus Research Site | Bristol | United Kingdom |
| Marinus Research Facility | Glasgow | United Kingdom |
| Marinus Research Site | London | United Kingdom |
| COMPLETED |
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| NOT COMPLETED |
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Safety Population
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | placebo suspension 3x's /day for 17 weeks Placebo: inactive |
| BG001 | Ganaxolone | ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks ganaxolone: active drug |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | ITT Population | Posted | Median | 95% Confidence Interval | Seizures per day | End of the double-blind 17 week treatment period |
|
|
| |||||||||||||||||||||||||||||||||||
| Secondary | 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 | Per Protocol Population | Posted | Count of Participants | Participants | End of the double-blind 17 week treatment period |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Intent to Treat Population | Posted | Count of Participants | Participants | End of the double-blind 17 week treatment period |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Intent to Treat Population | Posted | Count of Participants | Participants | End of the double-blind 17 week treatment period |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Clinical Global Impression of Improvement - Clinician | Clinical global impression of improvement during the double-blind treatment period of ganaxolone compared to placebo | ITT Population | Posted | Count of Participants | Participants | [Time Frame: End of the double-blind 17 week treatment period] |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | 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. | ITT Population | Posted | Mean | Standard Deviation | percent of seizure-free days | End of the double-blind 17 week treatment period |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | 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 | Intent to Treat Population | Posted | Mean | Standard Deviation | days | End of the double-blind 17 week treatment period |
|
| ||||||||||||||||||||||||||||||||||||
| Secondary | 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. | Intent to Treat Population | Posted | Count of Participants | Participants | End of the double-blind 17 week treatment period |
|
|
Screening through 17-week Double-blind Phase
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | placebo suspension 3x's /day for 17 weeks Placebo: inactive | 0 | 51 | 5 | 51 | 45 | 51 |
| EG001 | Ganaxolone | ganaxolone suspension (50 mg/ml) 3x's /day for 17 weeks ganaxolone: active drug | 0 | 50 | 6 | 50 | 43 | 50 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bronchitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Rhinovirus Infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Urinary Tract Infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Pneumonia Mycoplasmal | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Pneumonia Viral | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Respiratory Syncytial Virus Bronchiolitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Oxygen Saturation Decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Food Refusal | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
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| Pneumonia Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Faecaloma | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypotonia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Unresponsive to Stimuli | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Somnolence | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
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| Sedation | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
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| Hypersomnia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
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| Lethargy | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
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| Hyperaesthesia | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
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| Upper Respiratory Tract Infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Ear Infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Respiratory Tract Infection Viral | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Varicella | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Salivary Hypersecretion | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Abdominal Pain | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Gastrooesophageal Reflux Disease | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Gait Disturbance | General disorders | MedDRA 23.0 | Systematic Assessment |
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| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Insomnia | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| Irritability | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
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| Body Temperature Increased | Investigations | MedDRA 23.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
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| Seasonal Allergy | Immune system disorders | MedDRA 23.0 | Systematic Assessment |
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If the study is part of a multicenter study, the first publication of the study results shall be made by the sponsor in conjunction with the sponsor's presentation of a joint, multicenter publication of the compiled and analyzed study results.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Marinus Clinical Trials Submission Manager | Marinus Pharmaceuticals, Inc. | 484-801-4670 | clinicaltrials@marinuspharma.com |
| Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 29, 2019 | Apr 12, 2023 | SAP_003.pdf |
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| ID | Term |
|---|---|
| C564064 | CDKL5 deficiency disorder |
| D012640 | Seizures |
| D004827 | Epilepsy |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C105051 | ganaxolone |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Poland |
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| Italy |
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| United Kingdom |
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| Israel |
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| Australia |
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| France |
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| Russia |
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