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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Seizure in Participants With Tuberous Sclerosis Complex; Seizure in Participants With Dravet Syndrome; Seizure in Participants With Lennox-Gastaut Syndrome
• Intervention / Treatment: Drug: GWP42003-P

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 Type: Interventional
• Enrollment (Estimated): 27
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trial Disclosure & Transparency; Phone Number: 215-832-3750; Email: ClinicalTrialDisclosure@JazzPharma.com

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Recruiting
      • Clinical Trial Site
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • Clinical Trial Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Clinical Trial Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Clinical Trial Site
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Clinical Trial Site
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Clinical Trial Site
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Not yet recruiting
      • Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 1 year (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.).

Drug: GWP42003-P; Oral Solution; Other Names: Cannabidiol; Epidiolex; Epidyolex

What is the study measuring?

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		Week 12, and every 4 weeks thereafter, up to Week 52
Clinician Global Impression of Change/Severity (CGIC/S) Score	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 will be summed and the total will be reported. Higher scores indicate poor clinical outcome.	At Day 1 (Visit 3), Day 169 (Visit 13), and Day 365 (EOT)
Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) Score	The Infant and Toddler Quality of Life Questionnaire Short Form 47 (ITQOL-47) was developed for use in infants and toddlers from 12-months-to-5 years of age and assesses levels of health and well-being. The caregiver will complete the assessment on an electronic device. For each concept, item responses are scored, summed, and transformed on a scale from 0 (worst health) to 100 (best health). Higher scores indicate better clinical outcome.	At Baseline (Visit 1), Day 1 (Visit 3), and Day 365 (EOT)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Number of Treatment Responders	Treatment Responders are defined as participants with ≥ 50% reduction from baseline in caregiver-reported total countable seizures	Week 12, and every 4 weeks thereafter, up to Week 52

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2021
• Primary Completion (Estimated): January 22, 2025
• Study Completion (Estimated): January 22, 2025

Study Registration Dates

• First Submitted: July 21, 2020
• First Submitted That Met QC Criteria: July 21, 2020
• First Posted (Actual): July 24, 2020

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Epilepsy; Child; Children; Tuberous Sclerosis Complex; Pediatric; CBD; Infants; Seizures; GWP42003-P; Cannabidiol oral solution; Tumors; TSC; Cannabidiol; Infantile Spasms; Epidiolex; TSC1; TSC2; Tuberous Sclerosis; Seizure; Dravet Syndrome; Lennox-Gastaut Syndrome; Tuberous Sclerosis 1; Tuberous Sclerosis 2
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epileptic Syndromes; Neoplasms; Neurologic Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Neurocutaneous Syndromes; Epilepsy; Hamartoma; Neoplasms, Multiple Primary; Epilepsies, Myoclonic; Sclerosis; Syndrome; Seizures; Tuberous Sclerosis; Lennox Gastaut Syndrome; Anticonvulsants; Cannabidiol
• Other Study ID Numbers: GWEP17005; 2020-002132-67 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No