A Study to Assess Cannabidiol Oral Solution With Vigabatrin as Initial Therapy in Participants With Infantile Spasms

Study Overview
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Brief Summary
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The primary purpose of this study was to evaluate the efficacy, safety, and tolerability of Cannabidiol Oral Solution (CBD) as adjunctive therapy with vigabatrin as initial therapy, compared to vigabatrin alone in the treatment of infants newly diagnosed with Infantile Spasms (IS).

Detailed Description
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This was a randomized, double-blind, placebo-controlled, parallel-group study in which participants were randomized in a 1:1 ratio to 1 of 2 treatment groups. During the Initial Treatment Period, participants received either vigabatrin plus CBD or vigabatrin plus matching placebo and were dosed approximately every 12 hours, with a meal. This study was comprised of five periods: Screening, Initial Treatment, Extended Treatment, Taper, and Follow up Periods, with a maximum duration of approximately 140 days.

Official Title
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A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Efficacy, Safety, and Tolerability of Cannabidiol Oral Solution as Adjunctive Therapy With Vigabatrin as Initial Therapy in Patients With Infantile Spasms

Conditions
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Infantile Spasm

Intervention / Treatment
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* Drug: Cannabidiol Oral Solution
* Drug: Placebo
* Drug: Vigabatrin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parent(s)/caregiver(s) fully comprehends and signs the informed consent form, understands all study procedures, and can communicate satisfactorily with the Investigator and study coordinator, in accordance with applicable laws, regulations, and local requirements. Clinical diagnosis of Infantile Spasms, confirmed by video-EEG (including at least one cluster of electroclinical spasms [≥3 in any 10-minute epoch] and hypsarrythmia) obtained during the Screening Period and read by a central reader. General good health (defined as the absence of any clinically relevant abnormalities as determined by the Investigator) based on physical and neurological examinations, medical history, and clinical laboratory values completed during the Screening Visit). In the opinion of the investigator, the parent(s)/caregiver(s) is (are) willing and able to comply with the study procedures and visit schedules. Exclusion Criteria: Is considered by the investigator, for any reason (including, but not limited to, the risks described as precautions, warnings, and contraindications in the current version of the Investigator's Brochure for Cannabidiol Oral Solution) to be an unsuitable candidate to receive the study drug. Known or suspected allergy to cannabidiol. History of an allergic reaction or a known or suspected sensitivity to any substance that is contained in the investigational product formulation. Use of any cannabidiol/cannabis product within 30 days of study entry. Participant is diagnosed or suspected of having tuberous sclerosis. Participant has received treatment with either vigabatrin, ACTH, or high-dose steroids previously. Previous or concomitant therapy with felbamate, clobazam, valproic acid, or the ketogenic diet. Participant currently on any disallowed CYP3A4-related medication (phenytoin, fluvoxamine, carbamazepine, and St. John's Wort). Previously received any investigational drug or device or investigational therapy within 30 days before Screening. Clinically significant abnormal laboratory values, including: liver function tests (LFTs) such as albumin, direct bilirubin, total bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≥3 times the upper limit of normal (ULN). The investigator may deem the participant eligible if he or she judges the laboratory values to be not clinically significant.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 24 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CBD with Vigabatrin<br>Participants received up to 40 milligrams per kilogram per day (mg/kg/day) divided twice daily (BID) of CBD with food. Participants also received up to 150 mg/kg/day BID of vigabatrin with food. | Drug: Cannabidiol Oral Solution<br>* An oral solution containing pharmaceutical grade cannabidiol (nonplant-based).<br>Drug: Vigabatrin<br>* Powder suspension<br>* Other names: Sabril;|
| Placebo Comparator: Placebo with Vigabatrin<br>Participants received a matching placebo to CBD with food, and also received up to 150 mg/kg/day BID of vigabatrin with food. | Drug: Placebo<br>* Matching oral solution<br>Drug: Vigabatrin<br>* Powder suspension<br>* Other names: Sabril;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Considered Complete Responders | Complete response is defined as complete resolution of spasms and hypsarrhythmia confirmed by 24-hour video-electroencephalogram (EEG). | Up to Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Resolution of Infantile Spasms | Resolution of IS was assessed by 24-hour video-EEG. | Up to Day 15 | 
| Percentage of Participants With Resolution of Hypsarrhythmia | Resolution of hypsarrhythmia was assessed by 24-hour video-EEG. | Up to Day 15 | 
| Investigator Impression of Efficacy and Tolerability of Study Drug Clinical Global Impression- Global Improvement (CGI-I) | Investigators will use the CGI-I scale, which is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention and is rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. Higher scores indicated worse condition. | Day 15 | 
| Percentage of Participants With Increase in Number of Spasm-Free Days Between Day 1 and Day 15 | Increase in spasm-free days will be determined by seizure diary entries. | Up to Day 15 | 
| Percentage of Participants With Complete Response During the Initial Treatment Period Who Relapse During the Extended Treatment Period | Relapse during the extended treatment period will be confirmed by video-EEG following parent report of relapse. | Up to Day 75 | 
| Time to Relapse During the Extended Treatment Period |  | Up to Day 75 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infantile spasm, Vigabatrin, Cannabidiol oral solution