Assessment of Adjunctive Cannabidiol Oral Solution (GWP42003-P) in Children With Tuberous Sclerosis Complex (TSC), Dravet Syndrome (DS), or Lennox-Gastaut Syndrome (LGS) Who Experience Inadequately-controlled Seizures

Study Overview
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Brief Summary
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This study will be conducted to evaluate the safety, pharmacokinetics (PK), and efficacy of adjunctive GWP42003-P in participants < 2 years of age with tuberous sclerosis complex (TSC), Lennox-Gastaut syndrome (LGS), or Dravet syndrome (DS).

Detailed Description
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The study duration will be up to approximately 62 weeks, including a 4-week screening/baseline period, a 52-week dose optimization treatment period (which includes a fixed 2-week titration period followed by flexible dose optimization), a 10-day taper period, and a safety follow-up period (4 weeks after the end-of-taper visit).

Official Title
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An Open-label, Single-arm Study to Assess the Safety, Pharmacokinetics, and Efficacy of Adjunctive Cannabidiol Oral Solution (GWP42003-P) in Participants With Tuberous Sclerosis Complex (Age 1 Month to < 2 Years of Age), Dravet Syndrome (1 Year to < 2 Years of Age), or Lennox-Gastaut Syndrome (1 Year to < 2 Years of Age) Who Experience Inadequately-controlled Seizures

Conditions
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Seizure in Participants With Tuberous Sclerosis Complex, Seizure in Participants With Dravet Syndrome, Seizure in Participants With Lennox-Gastaut Syndrome

Intervention / Treatment
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* Drug: GWP42003-P


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participants with TSC (1 month to < 2 years of age), or DS (1 year to < 2 years of age), or LGS (1 year to < 2 years of age) within the specified age range at the time of initial informed consent. Parent(s)/legal representative is/are willing and able to give informed consent for participation in the study. Parent(s)/legal representative is/are willing and able (in the investigator's opinion) to comply with all study requirements (including accurate electronic participant-reported outcome [ePRO] diary completion). Participants with TSC must have a diagnosis per the 2012 International Tuberous Sclerosis Complex Consensus Conference. Participants with LGS or DS must have a diagnosis that is consistent with International League Against Epilepsy (ILAE) guidelines and confirmed by the Epilepsy Study Consortium (ESCI). Participants who have uncontrolled seizures, and who are currently receiving 1 or more antiseizure medication (ASMs). A suitable VEEG, as available in the medical record, within 1 year of Visit 1. When a historical VEEG is not available, and if clinically indicated and appropriate (due to uncertainties or new seizures), a VEEG will be completed and read to confirm diagnosis prior to Visit 3. All VEEGs are to be read at baseline by the investigator and by an independent reviewer. Has seizures which are not adequately controlled through their current ASMs, defined as ≥ 1 seizure reported on the seizure diary during the screening/baseline period Key Exclusion Criteria: Has tumor growth which, in the opinion of the investigator, could affect participant safety. Has clinically significant abnormal laboratory values, in the investigator's opinion, at screening/baseline. Has clinically significant abnormalities in the electrocardiogram (ECG) measured at screening/baseline. Has any concurrent cardiovascular conditions, that will, in the investigator's opinion, interfere with the ability to assess their ECGs. Has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the study intervention such as sesame seed oil. Has significantly impaired hepatic function prior to Visit 3, defined as: Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × upper limit of normal (ULN) and (total bilirubin [TBL] > 2 × ULN or international normalized ratio [INR] > 1.5). Serum ALT or AST > 5 × ULN. Serum ALT or AST > 3 × ULN with the presence of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (> 5%). Elevated ALT or AST should be discussed with the medical monitor prior to Visit 3; the medical monitor may allow for a confirmatory re-draw prior to Visit 3. Has any other clinically significant disease or disorder which, in the opinion of the investigator, may either put the participant, other participants, or site staff at risk because of participation in the study, may influence the result of the study, or may affect the participant's ability to take part in the study. Any clinically significant abnormalities identified following a physical examination of the participant that, in the opinion of the investigator, would jeopardize the safety of the participant if they took part in the study. Has previously been enrolled into this study. Has plans to travel outside their country of residence during the study, unless the participant has confirmation that the study intervention is permitted in the destination country. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 23 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>The 52-week treatment period includes a fixed 2-week titration schedule followed by flexible dose optimization. Day 1: 5 mg/kg/day (2.5 mg/kg twice daily (b.i.d.)) Day 8: 10 mg/kg/day (5 mg/kg b.i.d.) Day 15 to Week 52: Flexible dosing based on the participant's observed efficacy, safety, and tolerability per the investigator's clinical judgement. Up to a maximum of 20 mg/kg/day (10 mg/kg b.i.d.) for LGS and DS or 25 mg/kg/day (12.5 mg/kg b.i.d.) for TSC, in maximum weekly increments of 5 mg/kg/day (≤ 2.5 mg/kg b.i.d.). | Drug: GWP42003-P<br>* Oral Solution<br>* Other names: Epidyolex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment-Emergent Adverse Events (TEAEs) |  | From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks | 
| Mean Change From Baseline in Blood Pressure |  | From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks | 
| Mean Change From Baseline in Pulse Rate |  | From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks | 
| Mean Change From Baseline in Respiration Rate |  | From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks | 
| Mean Change from Baseline in Body Temperature |  | From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks | 
| Mean Change From Baseline in Height |  | From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks | 
| Mean Change From Baseline in Body Weight |  | From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks | 
| Mean Change From Baseline in Heart Rate |  | From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks | 
| Mean Change From Baseline in RR Interval |  | From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks | 
| Mean Change From Baseline in PR Interval |  | From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks | 
| Mean Change From Baseline in QRS Duration |  | From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks | 
| Mean Change From Baseline in QT Interval |  | From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks | 
| Mean Change From Baseline in QTcB and QTcF |  | From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks | 
| Number of Participants with a Clinically Significant Change in Laboratory Parameters |  | From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks | 
| Number of Participants with Emergence of New Types of Seizures |  | From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks | 
| Plasma Concentrations of GWP42003-P and its Major Metabolites |  | Predose, 3 hours and 6 hours post dose on Days 1, 15, 29, 57, and End of Treatment (Week 52) | 
| Percentage Change from Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers and Investigators |  | Week 12, and every 4 weeks thereafter, up to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment Responders | Treatment Responders are defined as participants with ≥ 50% reduction from baseline in caregiver- and Investigator-Reported total countable seizures | Week 12, and every 4 weeks thereafter, up to Week 52 | 
| Percentage Change from Baseline in Total Countable Seizures | This endpoint includes the following changes in percentage of seizures: > 25% (increase); ≥ 0% to ≤ 25% (increase); > -25% to < 0% (reduction); > -50% to ≤ -25% (reduction); > -75% to ≤ -50% (reduction); ≤ -75% (reduction). | Week 12, and every 4 weeks thereafter, up to Week 52 | 
| Number of Participants Who Achieved Seizure-Free Status |  | Week 12, and every 4 weeks thereafter, up to Week 52 | 
| Percentage of Participants Still Receiving GWP42003-P |  | Week 12, and every 4 weeks thereafter, up to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epilepsy, Seizures, Infantile Spasms, Tumors, Pediatric, Children, Infants, Cannabidiol oral solution, GWP42003-P, Tuberous Sclerosis Complex, TSC, Tuberous Sclerosis, Cannabidiol, Epidiolex, CBD, Seizure, Child, TSC1, TSC2, Tuberous Sclerosis 1, Tuberous Sclerosis 2, Lennox-Gastaut Syndrome, Dravet Syndrome