Clinical trial NCT04485104: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Seizure in Participants With Tuberous Sclerosis Complex
Seizure in Participants With Dravet Syndrome
Seizure in Participants With Lennox-Gastaut Syndrome
Keywords: 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
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-07-24
Enrollment: 3
Sex: ALL
Minimum age (years): 1
Maximum age (years): 23
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Eligibility criteria: 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 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.

Primary outcomes:
measure: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks
measure: Mean Change From Baseline in Blood Pressure
timeFrame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks
measure: Mean Change From Baseline in Pulse Rate
timeFrame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks
measure: Mean Change From Baseline in Respiration Rate
timeFrame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks
measure: Mean Change from Baseline in Body Temperature
timeFrame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks
measure: Mean Change From Baseline in Height
timeFrame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks
measure: Mean Change From Baseline in Body Weight
timeFrame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks
measure: Mean Change From Baseline in Heart Rate
timeFrame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks
measure: Mean Change From Baseline in RR Interval
timeFrame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks
measure: Mean Change From Baseline in PR Interval
timeFrame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks
measure: Mean Change From Baseline in QRS Duration
timeFrame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks
measure: Mean Change From Baseline in QT Interval
timeFrame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks
measure: Mean Change From Baseline in QTcB and QTcF
timeFrame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks
measure: Number of Participants with a Clinically Significant Change in Laboratory Parameters
timeFrame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks
measure: Number of Participants with Emergence of New Types of Seizures
timeFrame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks
measure: Plasma Concentrations of GWP42003-P and its Major Metabolites
timeFrame: Predose, 3 hours and 6 hours post dose on Days 1, 15, 29, 57, and End of Treatment (Week 52)
measure: Percentage Change from Baseline in Indication-Specific Total Countable Seizures as Recorded by Caregivers
timeFrame: Week 12, and every 4 weeks thereafter, up to Week 52
measure: Clinician Global Impression of Change/Severity (CGIC/S) Score
timeFrame: At Day 1 (Visit 3), Day 169 (Visit 13), and Day 365 (EOT)
measure: Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score
timeFrame: At Baseline (Visit 1), Day 1 (Visit 3), and Day 365 (EOT)
Secondary outcomes:
measure: Number of Treatment Responders
timeFrame: Week 12, and every 4 weeks thereafter, up to Week 52
measure: Percentage Change from Baseline in Total Countable Seizures
timeFrame: Week 12, and every 4 weeks thereafter, up to Week 52
measure: Number of Participants Who Achieved Seizure-Free Status
timeFrame: Week 12, and every 4 weeks thereafter, up to Week 52
measure: Percentage of Participants Still Receiving GWP42003-P
timeFrame: Week 12, and every 4 weeks thereafter, up to Week 52
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Clinical Trial Site
state: Arkansas
city: Los Angeles
country: United States
facility: Clinical Trial Site
state: California
city: Chicago
country: United States
facility: Clinical Trial Site
state: Illinois
city: Boston
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Cincinnati
country: United States
facility: Clinical Trial Site
state: Ohio
city: Houston
country: United States
facility: Clinical Trial Site
state: Texas
city: Firenze
country: Italy
facility: Clinical Trial Site
city: Genova
country: Italy
facility: Clinical Trial Site
city: Rome
country: Italy
facility: Clinical Trial Site
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Madrid
country: Spain
facility: Clinical Trial Site
Study officials:
References: