Cannabidiol Oral Solution for Treatment of Refractory Infantile Spasms

Study Overview
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Brief Summary
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Infantile Spasms (IS) is a diagnosis described as a fairly rare and terrible form of epilepsy that usually strikes children in the first year of life. There is a great need for safe and effective therapies in the treatment of IS. This need is even more important for infants and toddlers still sick after being treated with medicine that is already available. This is a multi-center study to evaluate the efficacy and safety of Cannabidiol Oral Solution (CBD) in the treatment of children aged 6 months through 36 months with a diagnosis of infantile spasms who have not responded to first line therapies. The overall study duration is expected to be 64 weeks for those subjects who respond to CBD treatment. The maximum possible study duration for each patient is approximately 64 weeks, however a subject will be deemed to have completed the study after 58 weeks.

Detailed Description
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A protocol amendment in May 2016 created two parts to this trial: Part A (the extended treatment period) and Part B (the safety treatment period), whose objectives are as follows: Primary Part A: To evaluate the efficacy of Cannabidiol Oral Solution in treating refractory infantile spasms (IS). Secondary: Part A: To evaluate the safety of Cannabidiol Oral Solution in treating refractory infantile spasms. Part B: To assess the long-term safety of Cannabidiol Oral Solution as an adjunctive treatment for subjects with Infantile Spasms (IS) To establish the continued efficacy of Cannabidiol Oral Solution in maintaining seizure control in subjects with IS To assess the global status of subjects taking Cannabidiol Oral Solution for an extended period of time determined by various qualitative assessments To monitor for changes in plasma levels of Cannabidiol Oral Solution during long-term treatment of subjects with IS

Official Title
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A Phase 2 Study to Assess the Efficacy and Safety of Cannabidiol Oral Solution for the Treatment of Refractory Infantile Spasms

Conditions
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Spasms, Infantile

Intervention / Treatment
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* Drug: Cannabidiol Oral Solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets protocol-specified criteria for qualification, including infantile spasms Parent(s)/caregiver(s) fully comprehend and sign the informed consent form, understand all study procedures, and can communicate satisfactorily with the Investigator and study coordinator. Exclusion Criteria: History or current use of over-the-counter medications, dietary supplements, or drugs 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 analysis of results During the Safety Treatment and Follow-up Periods, subjects are not to receive the following: any cannabinoids (CBD, Δ9-tetrahydrocannabinol (THC), hemp oil, Realm Oil or marijuana) any other investigational drug or investigational device

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 36 Months

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cannabidiol Oral Solution: 20 or 40 mg/kg/day BID<br>The dose of Cannabidiol Oral Solution will begin at 20 mg/kg/day [10 mg/kg twice per day (BID)], will be adjusted at any time if the investigator feels the safety or well-being of the participant is at risk, and will be titrated up or down according to protocol-stipulated parameters and at the investigator's discretion after Day 14 to enhance efficacy. Dose will not exceed 40 mg/kg/day. | Drug: Cannabidiol Oral Solution<br>* 20 or 40 mg/kg/day BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Percentage of Participants Who Are Considered Complete Responders at Day 14 | Complete response was defined as complete resolution of spasms and hypsarrythmia (if present at baseline) confirmed by video-electroencephalogram (EEG) at Day 14. | Day 14 | 
| Part B: Percentage of Participants Experiencing Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), and Serious Adverse Events (SAEs) |  | Up to Week 64 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Percentage of Participants With Absence of Infantile Spasms at Day 14 |  | Day 14 | 
| Part A: Percentage of Participants With Absence of Hypsarrhythmia at Day 14 |  | Day 14 | 
| Part A: Median Reduction in Seizure-burden Comparing Video-EEG at Baseline to Repeat Video-EEG at Day 14 |  | Baseline, Day 14 | 
| Part A: Parent Impression of Efficacy and Tolerability of Study Drug | Parent impression of efficacy and tolerability, as measured by Clinical Global Impression-Global Improvement Scale (CGI-I), was summarized by visit and status of response (Complete/Partial and No Response) at Visit 3 (Day 14), Visit 4 (Week 4), Visit 5 (Week 8), Visit 6 (Week 10), and end of study. The CGI-I was also analyzed in a continuous scale, as follows: 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, and 7 = Very much worse | Visit 3 (Day 14), Visit 4 (Week 4), Visit 5 (Week 8), Visit 6 (Week 10), and end of study. | 
| Part A: Percentage of Participants With a Partial Response to Treatment | Partial response was defined as a substantive change in background EEG or reduction in spasms on video EEG obtained at Day 14. | Day 14 | 
| Part A: Percentage of Complete Responders With Relapse | Complete response was defined as complete resolution of spasms and hypsarrythmia (if present at baseline) confirmed by video-EEG at Day 14. | Day 14 | 
| Part A: Time to Complete Responder Relapse | Complete response was defined as complete resolution of spasms and hypsarrythmia (if present at baseline) confirmed by video-EEG at Day 14. | Day 14 | 
| Part B: Parent Impression of Efficacy and Tolerability of Study Drug as Measured by the Change in Clinical Global Impression of Improvement Assessment (CGI-I), Responses at Every Visit Throughout Part B |  | Up to Week 64 | 
| Part B: Investigator Impression of Efficacy and Tolerability of Study Drug as Measured by the Change in CGI-I Responses at Every Visit Throughout Part B |  | Up to Week 64 | 
| Part B: Median Reduction in Seizure-burden Comparing Seizure Diaries Throughout Part B. |  | Up to Week 64 | 
| Part B: Percentage of Participants Who Have a Relapse of Spasms Based on Video-EEG |  | Up to Week 64 | 
| Part B: Time to Relapse as Confirmed by Video-EEG |  | Up to Week 64 |