A Study to Investigate Behavioral and Other Co-Occurring Outcomes With Epidiolex as Add-On Therapy in Participants Aged 1 to 65 Years of Age With Tuberous Sclerosis Complex (EpiCom)

A Phase 4, Interventional, Multicenter, Open-Label, Single-Arm Study to Assess Behavioral and Other Co-occurring Outcomes Following Treatment With EPID(I/Y)OLEX as Add-on Therapy in Participants (Aged 1 to 65 Years Old) With Seizures Associated With Tuberous Sclerosis Complex

The purpose of this study is to investigate behavioral and other co-occurring outcomes with EPID(I/Y)OLEX as an add-on therapy in participants aged 1 to 65 years with tuberous sclerosis complex (TSC) who experience seizures.

Study Overview

• Status: Completed
• Conditions: Tuberous Sclerosis Complex Associated Neuropsychiatric Disease
• Intervention / Treatment: Drug: Cannabidiol Oral Solution [Epidiolex]

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6AB
      • Alberta Children's Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • BC Children's Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
• Poland
  • Warsaw, Poland, 04-736
    • The Children's Memorial Health Institute
• United Kingdom
  • Bristol, United Kingdom, BS1 3NU
    • University Hospitals Bristol NHS Foundation Trust
  • Sheffield, United Kingdom, 2TH
    • Sheffield Children's NHS Foundation Trust
  • England
    • London, England, United Kingdom, SE1 7EH
      • Evelina London Children's Hospital Guys St Thomas' NHS Foundation Trust, the Guy's Hospital
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University School of Medicine
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida Health - Department of Neurology
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Health, Miami
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Roseville, Minnesota, United States, 55113
      • Minnesota Epilepsy Group
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Atrium Health Wake Forest Baptist Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • Le Bonheur Children's Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston - Clinical Research Unit
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center - San Antonio
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia, Charlottesville

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Is within the required age range at the time of signing (or at the time of the participant's parent(s)/Legally Authorized Representative (LAR) signing) the informed consent or providing assent (as applicable):

   • Participants based in the US: 1 to 65 years of age, inclusive.
   • Participants based outside the US: 2 to 65 years of age, inclusive.
2. Has a confirmed clinical diagnosis of TSC with a history of seizures in accordance with the 2012 International Tuberous Sclerosis Complex Consensus Conference criteria.
3. Has behaviors (eg, aggression, impulsivity, temper tantrum, self-injury, hyperactivity, extreme shyness, mood swings, poor eye contact, repetitive behaviors, restlessness, difficulty getting along with peers, rigid/inflexible to procedure and/or change) that are considered moderate or severe per the CareGI-S at Screening.

4. Is taking 1 or more anti-seizure medicine (ASM) at a dose that has been stable for at least 4 weeks prior to Screening.

   • All medications or interventions for epilepsy (including ketogenic diet and any neurostimulation devices for epilepsy) must have been stable for 4 weeks prior to screening and any major changes to treatment regimens should be discussed with the medical monitor.

5. Is naïve to CBD-OS treatment or has been off CBD-OS treatment for at least 3 months prior to Screening.
6. Is willing to maintain any factors expected to affect seizures stable (eg, alcohol consumption, smoking, concomitant medication usage).

7. Is male or female

   1. Male participants:

      • Male participants are eligible to participate if they agree to the following during the intervention period and for at least 2 weeks, corresponding to the time needed to eliminate the study intervention after the last dose of study intervention:

      • Refrain from donating fresh unwashed semen. PLUS
      • Use a male condom in addition to a second method of acceptable contraception used by their female partners when having sexual intercourse with a women of childbearing potential (WOCBP) who is not currently pregnant.

   2. Female participants:

      • A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies:

        • Is a woman of nonchildbearing potential. OR
        • Is a WOCBP and using a contraceptive method that is highly effective, preferably with low user dependency during the study intervention period and for at least 3 months after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention.
      • A WOCBP must have a negative highly sensitive pregnancy test within 28 days before the first dose of study intervention.

Exclusion Criteria:

1. Has a clinically significant unstable medical condition other than epilepsy.
2. Has an illness during the 4 weeks prior to screening other than epilepsy which, in the investigator's opinion, could affect study outcomes.
3. Has TSC-specific tumor growth which, in the investigator's opinion, could affect the effectiveness endpoints.
4. Has previously undergone significant surgery for epilepsy that, in the investigator's opinion, may impact the assessment of outcomes.
5. Has initiated felbamate within the last 12 months prior to Screening.
6. Is currently using or has in the past used recreational or medicinal cannabis or synthetic cannabinoid-based medications within the 3 months prior to Screening and is not willing to undergo a 1-month washout period before being rescreened.
7. Has received an investigational medicinal product within the 3 months prior to the Screening Visit.
8. Has previously been assigned study intervention for this study or is currently enrolled in any other interventional study.
9. Has laboratory values at the Baseline Visit that are abnormal and of clinical significance in the investigator's opinion.
10. Participant has significantly impaired hepatic function at the Baseline Visit.
11. Has any history of suicidal behavior or any suicidal ideation of type 4 or 5 as evaluated with C-SSRS or Children's C-SSRS at the Screening Visit (for participants ≥ 4 years of age).
12. Has any known or suspected hypersensitivity to cannabinoids or any of the excipients of CBD-OS.
13. Has a known or suspected history of alcohol or substance abuse.

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: Cannabidiol Oral Solution; Participants who will receive the Cannabidiol Oral Solution (CBD-OS) titrated up to a dose of 12.5 mg/kg administered twice daily for a total dose of up to 25 mg/kg/day for 26 consecutive weeks. Participants will have the option to continue receiving the CBD-OS for an additional 26 weeks, for a total of 52 weeks.	Drug: Cannabidiol Oral Solution [Epidiolex]; 100 mg/ml Cannabidiol Oral solution; Other Names: Epidiolex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in sleep characteristics using the Children's Sleep Habits Questionnaire (CSHQ)		Baseline, Week 26
Change in sleep characteristics using the Pittsburgh Sleep Quality Index (PSQI)		Baseline, Week 26
Change in caregiver-reported assessment of Quality of Life (QOL) using Pediatric Quality of Life Survey Family Impact Module (PedsQL FIM)		Baseline, Week 26
Change in caregiver-reported assessment of family functioning using Pediatric Quality of Life Survey Family Impact Module (PedsQL FIM)		Baseline, Week 26
Change in assessment of QOL using Pediatric Quality of Life Inventory (PedsQL)		Baseline, Week 26
Change in caregiver impression of overall severity of symptoms (behavior and seizure control) using the Caregiver Global Impression of Severity (CareGI-S)		Baseline, Week 4, Week 13, Week 26, Week 52
Change in participant impression of overall severity of symptoms (behavior and seizure control) using the Patient Global Impression of Severity (PGI-S)		Baseline, Week 4, Week 13, Week 26, Week 52
Change in clinician impression of overall severity of symptoms (behavior and seizure control) using the Clinician Global Impression of Severity (CGI-S)		Baseline, Week 4, Week 13, Week 26, Week 52
Change in number of seizure-free days		Baseline, Week 4, Week 13, Week 26, Week 52
Number of participant inpatient hospitalizations due to epilepsy		Up to Week 52
Number of withdrawals due to Treatment Emergent Adverse Events (TEAEs)		Up to Week 52
Change in the most problematic behavior Numerical Rating Score (NRS) score within the TAND-SQ		Baseline, Week 13, Week 26, Week 52
Change in Tuberous Sclerosis Complex Associated Neuropsychiatric Disorders Self-report, Quantified Checklist (TAND-SQ) score		Baseline, Week 13, Week 26, Week 52
Change in Aberrant Behavior Checklist (ABC) score		Baseline, Week 13, Week 26, Week 52
Change in Child Behavior Checklist (CBCL) score		Baseline, Week 26, Week 52
Change in Adult Behavior Checklist (ABCL) score		Baseline, Week 26, Week 52
Change in Adult Self-Report (ASR) score		Baseline, Week 26, Week 52
Change in Patient-Reported Outcomes Measurement Information System (PROMIS) domains score		Baseline, Week 26, Week 52
Change in executive function using Behavior Rating Inventory of Executive Function (BRIEF)		Baseline, Week 26
Retention Rate	Retention rate is the number of participants continuing with CBD-OS treatment over total accrued participants	Baseline, Week 13, Week 26, Week 52
Number of participants considered treatment responders	Treatment responders will be reported as those with a 25%, 50%, 75% and 100% reduction in seizure frequency from baseline	Baseline, Week 4, Week 13, Week 26, Week 52
Number of participants experiencing a worsening, no change, or improvement in seizure frequency	Number of participants who experience a change in seizure frequency from baseline defined as: worsening (>25%); no change (-25 to + 25%); improvement (-25% to -50%, ≥-50% to -75%, ≥-75%)	Baseline, Week 4, Week 13, Week 26, Week 52
Change in ideation score per the Columbia-Suicide Severity Rating Scale (C-SSRS)		Baseline, Week 4, Week 13, Week 26, Week 52
Change in number of suicide attempts per the C-SSRS		Baseline, Week 4, Week 13, Week 26, Week 52
Change in ideation score per the Children's C-SSRS		Baseline, Week 4, Week 13, Week 26, Week 52
Change in number of suicide attempts per the Children's C-SSRS		Baseline, Week 4, Week 13, Week 26, Week 52

Collaborators and Investigators

• Sponsor: Jazz Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2023
• Primary Completion (Actual): April 6, 2026
• Study Completion (Actual): April 6, 2026

Study Registration Dates

• First Submitted: May 9, 2023
• First Submitted That Met QC Criteria: May 9, 2023
• First Posted (Actual): May 18, 2023

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Behavior; Seizures; GWP42003-P; Cannabidiol; Epidiolex; Epidyolex; Tuberous Sclerosis Complex (TSC); Tuberous Sclerosis Complex Associated Neuropsychiatric Disorders (TAND); JZP926; TSC Associated Neuropsychiatric Disorders
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neoplasms; Genetic Diseases, Inborn; Neurodegenerative Diseases; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Hamartoma; Neoplasms, Multiple Primary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Tuberous Sclerosis; Seizures; Behavior; Organic Chemicals; Hydrocarbons; Terpenes; Cannabinoids; Cannabidiol
• Other Study ID Numbers: JZP926-402; 2023-507426-17 (Other Identifier: EU CTR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with ICMJE requirements, Jazz Pharmaceuticals may provide qualified external researchers access to individual participant data (IPD) and clinical trial data that underlie the results of this trial upon request. Qualified researchers can submit a request on https://www.jazzpharma.com/science/clinical-trial-data-sharing/ as outlined. Jazz Pharmaceuticals reserves the right not to consider a request. For inquiries about Jazz's data sharing policy, contact clinicaldatasharing@jazzpharma.com

Drug and device information, study documents

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