Cannabidiol Oral Solution as an Adjunctive Treatment for Treatment-resistant Seizure Disorder

Study Overview
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Brief Summary
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This is a multicenter, open-label trial to assess the long-term safety and efficacy of Cannabidiol Oral Solution as adjunctive therapy for pediatric participants with treatment-resistant seizure disorders, including Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS). All participants have rolled over from previous trials: INS011-14-029 (NCT02324673) and INS011-15-054 (NCT02551731).

Official Title
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A Multicenter, Open-label, Flexible Dose Study to Assess the Long-term Safety of Pharmaceutical Cannabidiol Oral Solution as an Adjunctive Treatment for Pediatric Subjects With a Treatment-resistant Seizure Disorder Who Complete INS011-14-029 or Part A of INS011-15-054

Conditions
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Seizures

Intervention / Treatment
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* Drug: Cannabidiol Oral Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed activities through Day 11 in INS011-14-029 or Part A (Visit 6) INS011-15-054 Informed consent/assent (as applicable) was voluntarily provided by the participant and/or parent(s)/caregiver(s) in accordance with applicable laws, regulations, and local requirements Is medically stable with no anticipated changes in chronic medications in the opinion of the Investigator Continues to meet protocol-specified criteria for qualification and contraception, including treatment-resistant seizure disorder In the opinion of the Investigator, the subject and/or parent(s)/caregiver(s) are able to continue keeping accurate seizure diaries Exclusion Criteria: Inadequate supervision by parent(s)/caregiver(s) History or current use of dietary supplements, drugs or over-the counter medications outside protocol-specified parameters Signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise: the safety or well-being of the participant or study staff the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding) the analysis of results

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Infants<br>Participants 1 to<2 years of age. Participants who completed INS011-14-029 initiated this study on the dose with which they were being treated previously, and dose modifications were made at the Investigator's discretion if tolerability or efficacy issues were observed for a particular participant. The maximum daily dose was 40 mg/kg/day. Participants who enrolled from INS011-15-054 continued treatment with the dose at which they were being treated previously, and dose modifications were made at the Investigator's discretion if tolerability or efficacy issues were observed for a particular participant. The total daily dose, milligrams per kilograms per day (mg/kg/day), will be evenly split between morning and evening doses (12 hours apart). If tolerability issues arise, the participant's dose may be changed at the investigator's discretion. | Drug: Cannabidiol Oral Solution<br>* An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).<br>|
| Experimental: Children<br>Participants 2 to <12 years of age. Participants who completed INS011-14-029 initiated this study on the dose with which they were being treated previously, and dose modifications were made at the Investigator's discretion if tolerability or efficacy issues were observed for a particular participant.The maximum daily dose was 40 mg/kg/day. Participants who enrolled from INS011-15-054 continued treatment with the dose at which they were being treated previously, and dose modifications were made at the Investigator's discretion if tolerability or efficacy issues were observed for a particular participant. The total daily dose (mg/kg/day) will be evenly split between morning and evening doses (12 hours apart). If tolerability issues arise, the participant's dose may be changed at the investigator's discretion. | Drug: Cannabidiol Oral Solution<br>* An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).<br>|
| Experimental: Adolescents<br>Participants 12 to <17 years of age. Participants who completed INS011-14-029 initiated this study on the dose with which they were being treated previously, and dose modifications were made at the Investigator's discretion if tolerability or efficacy issues were observed for a particular participant. The maximum daily dose was 40 mg/kg/day. Participants who enrolled from INS011-15-054 continued treatment with the dose at which they were being treated previously, and dose modifications were made at the Investigator's discretion if tolerability or efficacy issues were observed for a particular participant. The total daily dose (mg/kg/day) will be evenly split between morning and evening doses (12 hours apart). If tolerability issues arise, the participant's dose may be changed at the investigator's discretion. | Drug: Cannabidiol Oral Solution<br>* An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events | An Adverse Event (AE) is any untoward medical occurrence in a subject administered a pharmaceutical product. It does not necessarily have a causal relationship with this treatment. | Up to Week 50 | 
| Percentage of Participants With Serious Adverse Events | A serious adverse event is any untoward medical occurrence ( whether considered to be related to investigational product or not) that at any dose results in death, is life threatening, requires inpatient hospitalization, results in disability/incapacity, is a congenital abnormality/ birth defect, or medically significant as determined by an investigator. | Up to Week 50 | 
| Percentage of Participants With Clinically Significant Change From Baseline in Laboratory Values | Laboratory values include chemistry and hematology, and urinary analysis. | Up to Week 50 | 
| Percentage of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings |  | Up to Week 48 | 
| Percentage of Participants With Clinically Significant Change From Baseline in Vital Signs |  | Up to Week 50 | 
| Change From Baseline in Trough Plasma Levels of Cannabidiol and Its 7-OH Metabolite |  | Up to Week 50 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vineland Adaptive Behavior Scales (VABS) | The Vineland Adaptive Behavior Scales measures the personal and social skills of individuals from birth through adulthood. Because adaptive behavior refers to an individual's typical performance of the day-to-day activities required for personal and social sufficiency, these scales assess what a person actually does, rather than what he or she is able to do. The Vineland Adaptive Behavior Scales, Second Edition (Survey Interview Form) is a measure of adaptive behavior in children, adolescents and adults. It yields an overall standard score (Adaptive Behavior Composite, ABC) and age standard scores in four domains. The 4 domains are Communication, Daily Living Skills, Motor Skills, and Maladaptive Behaviour Index. ABC scores have a mean of 100 and a standard deviation of 15 (range = 20 to 160). Higher scores suggest a higher level of adaptive functioning. A rise in standard scores from Baseline indicates improvement. The VABS will be completed for all participants. | Up to Week 48 | 
| Number of Participants With a Positive Response on the Columbia-Suicide Severity Rating Scale (C-SSRS) | For subjects 7 years of developmental age or older, the Columbia-Suicide Severity Rating Scale (C-SSRS) will be administered to access suicidality. The appropriate adult version will be used in subjects 12 years of (developmental) age and older. The investigator will determine the participant's developmental age. | Up to Week 50 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lennox-Gastaut syndrome, Dravet syndrome, Treatment-resistant seizures