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

• ClinicalTrials.gov Identifier: NCT04485104
• Recruitment Status: Recruiting
• First Posted: July 24, 2020
• Last Update Posted: May 10, 2023
• Sponsor: Jazz Pharmaceuticals
• Information provided by (Responsible Party): Jazz Pharmaceuticals

Tracking Information

• First Submitted Date: July 21, 2020
• First Posted Date: July 24, 2020
• Last Update Posted Date: May 10, 2023
• Actual Study Start Date: May 19, 2021
• Estimated Primary Completion Date: December 29, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 12, 2022)

• Number of Participants with Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From signing of informed consent up to the post-treatment safety follow-up visit; up to 62 Weeks ]
• Mean Change From Baseline in Height [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Week 12, and every 4 weeks thereafter, up to Week 52 ]

Original Primary Outcome Measures (submitted: July 21, 2020)

• Part A: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: From signing of informed consent up to the post-treatment, safety follow-up visit (Visit 14), up to approximately 162 days ]
• Part B: Number of Participants with TEAEs [ Time Frame: From signing of informed consent up to the post-treatment, safety follow-up visit (Visit 20), up to approximately 407 days ]

Current Secondary Outcome Measures (submitted: December 12, 2022)

• Number of Treatment Responders [ Time Frame: Week 12, and every 4 weeks thereafter, up to Week 52 ]
  Treatment Responders are defined as participants with ≥ 50% reduction from baseline in caregiver- and Investigator-Reported total countable seizures
• Percentage Change from Baseline in Total Countable Seizures [ Time Frame: Week 12, and every 4 weeks thereafter, up to Week 52 ]
  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).
• Number of Participants Who Achieved Seizure-Free Status [ Time Frame: Week 12, and every 4 weeks thereafter, up to Week 52 ]
• Percentage of Participants Still Receiving GWP42003-P [ Time Frame: Week 12, and every 4 weeks thereafter, up to Week 52 ]

Original Secondary Outcome Measures (submitted: July 21, 2020)

• Trough Plasma Concentrations of Cannabidiol OS and Its Major Metabolites, 7-OH-CBD and 7-COOH-CBD [ Time Frame: 60 minutes prior to the morning dose of investigational medicinal product on Day 1 (Visit 3), Day 15 (Visit 5), Day 29 (Visit 7), Day 57 (Visit 9), Day 85 (Visit 10), and Day 120 (Visit 12) ]
• Part A: Percent Change from Baseline in Caregiver- and Investigator-Reported Total Seizure Frequency [ Time Frame: Baseline; End of Taper Visit (Day 134) ]
• Part A: Number of Participants with a Greater than or Equal to 50% Reduction in Caregiver- and Investigator-Reported Total Seizure Frequency [ Time Frame: Baseline; End of Taper Visit (Day 134) ]
• Part A: Number of Participants in the Indicated Category of Worsening and Improvement from the Baseline Period as Compared to the Part A Treatment Period of Seizure Frequency as Recorded by Caregivers and Investigators [ Time Frame: Baseline; End of Taper Visit (Day 134) ]
• Part A: Change in Seizure Frequency from Baseline to the Part A End of Treatment Visit as Captured by Multichannel Video EEG (VEEG) [ Time Frame: Baseline; End of Treatment Visit (Day 120) ]
• Part A: Change in EEG Seizure Burden from Baseline as Compared to the Part A End of Treatment Visit [ Time Frame: Baseline; End of Treatment Visit (Day 120) ]
• Part A: Correlation of Seizures Recorded during VEEG with Clinical Seizures Recorded by Caregivers and Investigators [ Time Frame: up to the End of Treatment Visit (Day 120) ]
• Part A: Change from Baseline in Scores of the Infant Toddler Quality of Life (ITQOL-SF47) Questionnaire at Part A End of Treatment [ Time Frame: Baseline; End of Treatment Visit (Day 120) ]
• Part B: Change from Baseline in Scores of the ITQOL-SF47 Questionnaire at Part B End of Treatment [ Time Frame: Baseline; End of Treatment Visit (Day 365) ]
• Part B: Percent Change in Total Seizure Frequency as Recorded by Caregivers and Investigators [ Time Frame: Baseline; End of Taper Visit (Day 379) ]
• Part B: Trough Plasma Concentrations of Cannabidiol OS and Its Major Metabolites, 7-OH-CBD and 7-COOH-CBD [ Time Frame: 60 minutes prior to the morning dose of investigational medicinal product on Day 1 (Visit 1), Day 15 (Visit 3), Day 29 (Visit 5), Day 57 (Visit 7), Day 85 (Visit 8), Day 169 (Visit 11), Day 253 (Visit 14), and Day 365 (Visit 18) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

Drug: GWP42003-P

Oral Solution

Other Names:

• Cannabidiol
• Epidiolex
• Epidyolex

Study Arms

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.).

Intervention: Drug: GWP42003-P

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 12, 2022): 27
• Original Estimated Enrollment (submitted: July 21, 2020): 15
• Estimated Study Completion Date: December 27, 2024
• Estimated Primary Completion Date: December 29, 2023 (Final data collection date for primary outcome measure)

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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Month to 23 Months (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Clinical Trial Disclosure & Transparency; 215-832-3750; ClinicalTrialDisclosure@JazzPharma.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04485104
• Other Study ID Numbers: GWEP17005; 2020-002132-67 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Jazz Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Jazz Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Jazz Pharmaceuticals
• Verification Date: May 2023