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Safety, Pharmacokinetics, and Exploratory Efficacy Assessment of Adjunctive Cannabidiol Oral Solution (GWP42003-P) Compared With Standard of Care Antiseizure Medication, in Participants Age 1 Month to <12 Months of Age With Tuberous Sclerosis Complex Who Experience Inadequately-controlled Seizures

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ClinicalTrials.gov Identifier: NCT04485104
Recruitment Status : Recruiting
First Posted : July 24, 2020
Last Update Posted : January 13, 2022
Sponsor:
Information provided by (Responsible Party):
Jazz Pharmaceuticals

Brief Summary:
This study will be conducted to evaluate the safety, tolerability, and pharmacokinetics of GWP42003-P compared with standard of care (SOC) antiseizure medication (ASM), assessed during the 17-week treatment period.

Condition or disease Intervention/treatment Phase
Seizure in Participants With Tuberous Sclerosis Complex Drug: GWP42003-P Drug: SOC Phase 3

Detailed Description:
The study will be comprised of 2 parts: Part A will evaluate the safety and pharmacokinetics of cannabidiol oral solution (OS) compared with SOC ASM for a period of 17 weeks in participants with tuberous sclerosis complex (TSC). Participants will be randomized in a 1:1 ratio to 1 of the 2 treatment groups. The duration of Part A will be approximately 27 weeks total, which includes a 4-week screening/baseline period, and a 17-week treatment period (including a 2- to 5- week titration period). Participants who complete Part A and do not wish to continue into Part B will enter a 2-week taper period and a safety follow-up period (4 weeks after the end-of-taper visit). Participants who are randomized to SOC ASM at Visit 3 (randomization) in Part A will be given the option of fast-tracking to Part B after completing a minimum of 26 days post randomization. Part B will be available to participants who continue to meet all eligibility criteria, and for whom the investigator feels continued treatment in Part B represents a favorable risk-benefit assessment. Part B will evaluate the long-term safety, tolerability, and pharmacokinetics of cannabidiol OS for a period of 52 weeks in participants with TSC. All participants in Part B will receive cannabidiol OS. The duration of Part B will be approximately 59 weeks total, including a 52-week treatment period (including a 2- to 5-week titration period for those participants randomized to SOC treatment only in Part A), a 2-week taper period, and a safety follow-up period (4 weeks and end-of-taper visit).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Randomized Trial to Assess the Safety, Pharmacokinetics, and Exploratory Efficacy of Adjunctive Cannabidiol Oral Solution (GWP42003-P) Compared With Standard of Care Antiseizure Medication, in Patients Age 1 Month to Less Than 12 Months of Age With Tuberous Sclerosis Complex Who Experience Inadequately-controlled Seizures
Actual Study Start Date : May 19, 2021
Estimated Primary Completion Date : July 11, 2023
Estimated Study Completion Date : July 10, 2024


Arm Intervention/treatment
Experimental: Standard of care (SOC) plus GWP42003-P Drug: GWP42003-P
100 milligrams/milliliter cannabidiol
Other Names:
  • Cannabidiol
  • Epidiolex
  • Epidyolex

Drug: SOC
SOC with participant's current antiseizure medication

Active Comparator: SOC Drug: SOC
SOC with participant's current antiseizure medication




Primary Outcome Measures :
  1. 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 ]
  2. Part A: Number of Participants with a Clinically Significant Change in Vital Sign Findings [ Time Frame: From signing of informed consent up to the post-treatment, safety follow-up visit (Visit 14); up to approximately 162 days ]
  3. Part A: Number of Participants with a Clinically Significant Change in Physical Examination Findings [ Time Frame: From signing of informed consent up to the post-treatment, safety follow-up visit (Visit 14); up to approximately 162 days ]
  4. Part A: Number of Participants with a Clinically Significant Change in 12-Lead Electrocardiogram (ECG) Findings [ Time Frame: From signing of informed consent up to the post-treatment, safety follow-up visit (Visit 14); up to approximately 162 days ]
  5. Part A: Number of Particpants with a Clinically Significant Change in Laboratory Parameters [ Time Frame: From signing of informed consent up to the post-treatment, safety follow-up visit (Visit 14); up to approximately 162 days ]
  6. Part A: Number of Participants with New Types of Seizure [ Time Frame: From signing of informed consent up to the post-treatment, safety follow-up visit (Visit 14); up to approximately 162 days ]
  7. 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 ]
  8. Part B: Number of Participants with Clinically Significant Vital Sign Findings [ Time Frame: From signing of informed consent up to the post-treatment, safety follow-up visit (Visit 20), up to approximately 407 days ]
  9. Part B: Number of Participants with a Clinically Significant Change in Physical Examination Findings [ Time Frame: From signing of informed consent up to the post-treatment, safety follow-up visit (Visit 20), up to approximately 407 days ]
  10. Part B: Number of Participants with a Clinically Significant Change in 12-Lead ECG Findings [ Time Frame: From signing of informed consent up to the post-treatment, safety follow-up visit (Visit 20), up to approximately 407 days ]
  11. Part B: 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 (Visit 20), up to approximately 407 days ]
  12. Part B: Number of Participants with New Types of Seizure [ Time Frame: From signing of informed consent up to the post-treatment, safety follow-up visit (Visit 20), up to approximately 407 days] ]

Secondary Outcome Measures :
  1. Part A: Plasma Concentrations of Cannabidiol OS and Its Major Metabolites (Trough, 3-hour, 6-hour post-dose) for Participants Randomized to GWP42003-P in Part A [ 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), and Day 120 (Visit 12); 3-hour and 6-hour postdose on Day 57 (Visit 9) and Day 120 (Visit 12) ]
  2. Part A: Percent Change from Baseline in Caregiver- and Investigator-Reported Total Countable Seizure Frequency [ Time Frame: Baseline; End of Taper Visit (Day 134) ]
  3. Part A: Proportion of Participants with a Greater than or Equal to 50% Reduction in Caregiver- and Investigator-Reported Total Countable Seizure Frequency [ Time Frame: Baseline; End of Taper Visit (Day 134) ]
  4. 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 Countable Seizure Frequency as Recorded by Caregivers and Investigators [ Time Frame: Baseline; End of Taper Visit (Day 134) ]
  5. Part A: Number of Participants Who Achieved Seizure-free Status [ Time Frame: Baseline; End of Taper Visit (Day 134) ]
  6. Part A: Change in Seizure Frequency from Baseline to the Part A End of Treatment Visit as Captured by Multichannel Video Electroencephalogram (VEEG) [ Time Frame: Baseline; End of Treatment Visit (Day 120) ]
  7. 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) ]
  8. Part A: Correlation of Seizures Recorded During Multichannel VEEG With Countable Clinical Seizures Recorded by Caregivers and Investigators [ Time Frame: up to the End of Treatment Visit (Day 120) ]
  9. Part A: Change from Baseline in Scores of the Infant Toddler Quality of Life-Short Form 47 (ITQOL-SF47) Questionnaire at Part A End of Treatment [ Time Frame: Baseline; End of Treatment Visit (Day 120) ]
  10. 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) ]
  11. Part B: Percent Change in Total Countable Seizure Frequency as Recorded by Caregivers and Investigators [ Time Frame: Baseline; End of Taper Visit (Day 379) ]
  12. Part B: Number of Participants Who Achieved Seizure-free Status [ Time Frame: Baseline; End of Taper Visit (Day 379) ]
  13. Part B: Plasma Concentrations of Cannabidiol and Its Major Metabolites (Trough, 3-hour, 6-hour post-dose) for Participants Randomized to Standard of Care in Part A [ 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), and Day 365 (Visit 18); 3-hour and 6-hour post dose on Day 57 (Visit 7) and Day 365 (Visit 18) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   1 Month to 11 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must be 1 month to < 12 months of age at the time of initial informed consent
  • Parent(s)/legal representative is/are willing and able to give informed consent for participation in the trial.
  • Parent(s)/legal representative is/are willing and able (in the investigator's opinion) to comply with all trial requirements (including accurate electronic participant-reported outcome [ePRO] diary completion).
  • Must have a clinical diagnosis of tuberous sclerosis complex (TSC) according to the investigator and as defined by 2012 International TSC Consensus Conference and International League Against Epilepsy (ILAE) Classification.
  • Multichannel (minimum 8-channel) 8- to 24-hour video electroencephalogram (VEEG), to be read prior to Part A Visit 3 by the investigator and an independent reviewer, for confirmation of diagnosis of inadequately-controlled seizures (may be collected from the participant's medical record if suitable).
  • Has seizures which are not adequately controlled through their current antiseizure medications (ASMs), defined as ≥ 1 seizure reported on the paper and ePRO seizure diary during the baseline period

Part B Only:

  • Has completed Visit 12 of Part A, if randomized to GWP42003-P and SOC ASM or completed at least 26 days of Part A if randomized to SOC ASM.
  • Was compliant with all requirements of Part A (e.g., dosing, paper and ePRO diary, participant visits/procedures), in the opinion of the investigator and sponsor.
  • Investigator considers continued treatment in a 1-year extension trial represents a favorable risk-benefit assessment for the participant.

Exclusion Criteria:

Part A Only:

  • 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 or baseline.
  • Has clinically significant abnormalities in the electrocardiogram (ECG) measured at screening or randomization. Including, QT interval corrected for heart rate with Bazett's formula (QTcB), of > 460 milliseconds (msec) on ECG.
  • Has any concurrent cardiovascular conditions, which 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 investigational medicinal product (IMP) such as sesame seed oil.
  • Has significantly impaired hepatic function prior to randomization, 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).
    • Elevated ALT or AST should be discussed with the medical monitor prior to randomization; the medical monitor may allow for a confirmatory re-draw prior to randomization.
  • Has any other clinically significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the trial, may influence the result of the trial, or may affect the participant's ability to take part in the trial.
  • 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 trial.
  • Has previously been randomized into this trial.
  • Has plans to travel outside their country of residence during the trial, unless the participant has confirmation that the IMP is permitted in the destination country.

Part B Only:

  • Has tumor growth which, in the opinion of the investigator, could affect the primary endpoint.
  • Has clinically significant abnormalities in the ECG in Part A. Including, QTcB of > 460 msec on ECG.
  • Has any concurrent cardiovascular conditions, which 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 IMP such as sesame seed oil.
  • Has significantly impaired hepatic function prior to Part B, defined as:

    • Serum ALT or AST > 3 × ULN and (TBL > 2 x ULN or INR > 1.5).
    • Elevated ALT or AST should be discussed with the medical monitor prior to rollover in Part B; the medical monitor may allow for a confirmatory redraw prior to rollover.
  • Has any other clinically significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the trial, may influence the result of the trial, or may affect the participant's ability to take part in the trial.
  • 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 trial.
  • Has previously been enrolled in Part B of this trial.
  • Has plans to travel outside their country of residence during the trial, unless the participant has confirmation that the IMP is permitted in the destination country.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04485104


Contacts
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Contact: Medical Enquiries 1-833-424-6724 medinfo@gbio.com

Locations
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United States, Arkansas
Clinical Trial Site Recruiting
Little Rock, Arkansas, United States, 72202
United States, California
Clinical Trial Site Recruiting
Los Angeles, California, United States, 90095
United States, Illinois
Clinical Trial Site Recruiting
Chicago, Illinois, United States, 60611
United States, Ohio
Clinical Trial Site Recruiting
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Jazz Pharmaceuticals
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Responsible Party: Jazz Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04485104    
Other Study ID Numbers: GWEP17005
2020-002132-67 ( EudraCT Number )
First Posted: July 24, 2020    Key Record Dates
Last Update Posted: January 13, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jazz Pharmaceuticals:
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
Additional relevant MeSH terms:
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Tuberous Sclerosis
Seizures
Sclerosis
Pathologic Processes
Neurologic Manifestations
Nervous System Diseases
Hamartoma
Neoplasms
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Malformations of Cortical Development, Group I
Malformations of Cortical Development
Nervous System Malformations
Neurocutaneous Syndromes
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Congenital Abnormalities
Genetic Diseases, Inborn
Cannabidiol
Anticonvulsants