Trial of Cannabidiol (CBD; GWP42003-P) for Infantile Spasms (GWPCARE7)

Study Overview
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Brief Summary
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This trial consists of 3 parts: a pilot safety phase, a pivotal randomized controlled phase, and an open-label extension phase. The pilot phase only will be described in this record. 2 cohorts of 5 participants will be enrolled sequentially. All participants will receive GWP42003-P.

Official Title
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A Randomized, Double-blind, Placebo-controlled Trial to Investigate the Efficacy and Safety of Cannabidiol (CBD; GWP42003-P) in Infants With Infantile Spasms Following an Initial Open-label Pilot Study

Conditions
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Infantile Spasms

Intervention / Treatment
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* Drug: GWP42003-P


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participant is aged 6- 24 months (inclusive) in the first cohort or aged 1-24 months (inclusive) in the second cohort, at the time of consent. Participant is diagnosed with IS and has failed to respond adequately following treatment with 1 or more approved IS therapies. To be considered hypsarrhythmia, as defined for use in the study, the electroencephalography (EEG) background must be slowed and have multifocal spikes. In addition, it must be either high voltage (above 300 µV) or have electrodecrement/discontinuity. Key Exclusion Criteria: Participant is currently taking or has taken clobazam or any mammalian target of rapamycin (mTOR) inhibitor within the 2 weeks prior to the screening visit. Participant has a QT interval, corrected for heart rate with Bazett's formula (QTcB), of 460 msec or greater on ECG. Participant's caregiver is currently giving or has given recreational or medicinal cannabis, or synthetic cannabinoid-based medications, within the 1 month prior to the screening visit. Participant's caregiver is unwilling to abstain from giving the participant (including the participant's mother abstaining themselves, if breastfeeding)recreational or medicinal cannabis, or synthetic cannabinoid-based medications (other than the study drug) during the trial. Participant has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the study drug, such as sesame oil. Participant has significantly impaired hepatic function at the screening visit. Participant has received an investigational medicinal product as part of a clinical trial within a minimum of 5 half-lives prior to the screening visit.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GWP42003-P<br>Administered orally, titrating to a target dose of 40 mg/kg/day. Participants continue at the target dose, or the highest tolerated dose up to the target dose, for the remainder of the 2-week treatment period. | Drug: GWP42003-P<br>* Clear, colorless to yellow solution containing cannabidiol dissolved in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.<br>* Other names: Cannabidiol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Severe Treatment-emergent Adverse Events (TEAEs) | TEAEs are defined as all adverse events not present prior to the first investigational medicinal product (IMP) or placebo administration or any event already present that worsened in severity or frequency following IMP. | From signing of informed consent up to Day 15 | 
| Number of Participants With Any Low or High Hematology Laboratory Parameter Value |  | Day 4 and Day 15 | 
| Number of Participants With Any Low or High Biochemistry Laboratory Parameter Value |  | Day 4 and Day 15 | 
| Number of Participant With Any Clinically Relevant Urinalysis Parameter Value | Clinical relevance was determined by the investigator. | Day 4 and Day 15 | 
| Number of Participants With Clinically Significant Electrocardiogram Findings | Clinical significance was determined by the investigator. | From signing of informed consent up to Day 15 | 
| Number of Participants With Clinically Significant Physical Examination Findings | Clinical significance was determined by the investigator. | From signing of informed consent up to Day 15 | 
| Number of Participants With Clinically Significant Vital Sign Findings | Clinical significance was determined by the investigator. | From signing of informed consent up to Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Free of Clinical Spasms | Clinical spasms were determined by video-electroencephalography (VEEG) for at least 8 hours and up to 24 hours. | Day 15 | 
| Percentage of Participants Free of Clinical Spasms | Clinical spasms were determined by VEEG for at least 8 hours and up to 24 hours. | Day 15 | 
| Number of Participants With Resolution of Hypsarrhythmia | Resolution of hypsarrhythmia was determined by VEEG for at least 8 hours and up to 24 hours. | Day 15 | 
| Percentage of Participants With Resolution of Hypsarrhythmia | Resolution of hypsarrhythmia was determined by VEEG for at least 8 hours and up to 24 hours. | Day 15 | 
| Number of Participants Experiencing Spasms and Seizures by Subtype | Caregivers recorded the participant's spasms and seizures by category in a daily diary. Subtypes of spasms and seizures included: clonic, tonic-clonic, myoclonic, focal, and absence. | Day 4 and Day 15 | 
| Average Time to Cessation of Spasms | Analysis could not be conducted for this outcome measure because the study met No Go Criteria. The Pilot Phase concluded after 9 participants completed treatment and demonstrated continued hypsarrhythmia and spasms on follow-up VEEG. The Pivotal Phase was not initiated; however, participants completing the Pilot Phase could roll into the Open Label Extension Phase (NCT02954887) for up to 1 year. | Day 1 to start of Open-label Extension (OLE) Phase | 
| Caregiver Clinical Global Impression of Change (CGIC) | The CGIC is a single-question assessment completed by the caregiver. The question assessed the status of the participant's condition since treatment start. The caregiver provided a rating on a 7-point scale from 1 (very much improved) to 7 (very much worse). | Day 15 | 
| Physician Global Impression of Change (PGIC) | The PGIC is a single-question assessment completed by the investigator. The question assesses the status of the participant's condition since treatment start. The investigator provided a rating on a 7-point scale from 1 (very much improved) to 7 (very much worse). | Day 15 | 
| Number of Responders | A responder is defined as a participant experiencing a resolution of hypsarrhythmia and free of spasms. Testing for responders was conducted by VEEG for at least 8 hours and up to 24 hours. | Baseline to Day 15 | 
| Percentage of Responders | A responder is defined as a participant experiencing a resolution of hypsarrhythmia and free of spasms. Testing for responders was conducted by VEEG for at least 8 hours and up to 24 hours. | Baseline to Day 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GWP42003-P, Cannabidiol