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
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Sponsor
- Jazz Pharmaceuticals
- Enrollment
- 3
- Locations
- 1
- Primary Endpoint
- Mean Change From Baseline in Blood Pressure
Study Overview
Brief Summary
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
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).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 1 Month to 23 Months (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •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
- •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
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
- •Has received another study intervention within 4 weeks prior to Visit 1 or plans to take another study intervention during the study.
- •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.
Arms & Interventions
GWP42003-P
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.).
Intervention: GWP42003-P (Drug)
Outcomes
Primary Outcomes
Mean Change From Baseline in Blood Pressure
Time Frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Mean Change From Baseline in Pulse Rate
Time Frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: From start of treatment to the post-treatment safety follow-up visit, up to 62 weeks
Mean Change From Baseline in Respiratory Rate
Time Frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Mean Change From Baseline in Body Temperature
Time Frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Mean Change From Baseline in Height
Time Frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Mean Change From Baseline in Body Weight
Time Frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Mean Change From Baseline in Heart Rate
Time Frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Mean Change From Baseline in RR Interval
Time Frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Mean Change From Baseline in PR Interval
Time Frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Mean Change From Baseline in QRS Duration
Time Frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Mean Change From Baseline in QT Interval
Time Frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Mean Change From Baseline in QTcB and QTcF
Time Frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Number of Participants With a Clinically Significant Change in Laboratory Parameters
Time Frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Number of Participants With Emergence of New Types of Seizures
Time Frame: From baseline up to the end of taper follow-up visit (Visit 20), up to 62 weeks
Plasma Concentrations of GWP42003-P and Its Major Metabolites
Time Frame: Predose, 3 hours and 6 hours post dose at End of Treatment (Week 52)
Number of Participants Based on Percentage Change From Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers
Time Frame: Day 1 up to Taper Period, up to Week 52
Clinician Global Impression of Severity (CGI/S) Score
Time Frame: At Day 365 (EOT)
The CGIC/S is a comprehensive neurodevelopmental assessment that covers the following domains: sensory, motor, cognition, emotional/behavioral health, communication, social, and adaptive functioning. This assessment is a 2-question survey per domain to be completed by the clinician. Individual domain scores are reported. The severity of impairment in each domain is rated by the clinician in a scale of 1 through 7 where 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill. Higher scores indicate poor clinical outcome.
Clinician Global Impression of Change (CGI/C) Score
Time Frame: At Day 365 (EOT)
The CGI/C is a comprehensive neurodevelopmental assessment that covers the following domains: sensory, motor, cognition, emotional/behavioral health, communication, social, and adaptive functioning. This assessment is a 2-question survey per domain to be completed by the clinician. Individual domain scores are reported. The severity of impairment in each domain is rated by the clinician in a scale of 1 through 7 where 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill. Higher scores indicate poor clinical outcome.
Secondary Outcomes
- Number of Treatment Responders(Day 1 up to the taper period, up to Week 52)
- Number of Participants Who Achieved Seizure-Free Status(Week 12, and every 4 weeks thereafter, up to date of withdrawal or Week 24, whichever occurs first)
- Percentage of Participants Still Receiving GWP42003-P(Week 12, and every 4 weeks thereafter, up to date of withdrawal or Week 24, whichever occurs first)