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

NCT05864846 | Completed Phase 4 FDA Drug

• 2 other identifiers: JZP926-4022023-507426-17
• Study Type: interventional
• Target: 79
• Locations: 4 countries
• Sites: 19

Brief Summary

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.

Conditions

Tuberous Sclerosis Complex Associated Neuropsychiatric Disease

Keywords

Seizures; Tuberous Sclerosis Complex (TSC); Tuberous Sclerosis Complex Associated Neuropsychiatric Disorders (TAND); Epidiolex; Epidyolex; GWP42003-P; JZP926; TSC Associated Neuropsychiatric Disorders; Cannabidiol; Behavior

Outcome Measures

Primary Outcomes (26)

• 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 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 executive function using Behavior Rating Inventory of Executive Function (BRIEF)

  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

• 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

• Change in number of seizure-free days

  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: 1. worsening (\>25%) 2. no change (-25 to + 25%) 3. 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

• 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

Study Arms (1)

Cannabidiol Oral Solution

EXPERIMENTAL

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]

Interventions

Cannabidiol Oral Solution [Epidiolex] DRUG

100 mg/ml Cannabidiol Oral solution

Also known as: Epidiolex

Cannabidiol Oral Solution

Eligibility Criteria

• Age: 1 Year - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Has a confirmed clinical diagnosis of TSC with a history of seizures in accordance with the 2012 International Tuberous Sclerosis Complex Consensus Conference criteria.
• 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.
• 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.
• Is naïve to CBD-OS treatment or has been off CBD-OS treatment for at least 3 months prior to Screening.
• Is willing to maintain any factors expected to affect seizures stable (eg, alcohol consumption, smoking, concomitant medication usage).
• Is male or female
• 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.
• Female participants:

You may not qualify if:

• Has a clinically significant unstable medical condition other than epilepsy.
• Has an illness during the 4 weeks prior to screening other than epilepsy which, in the investigator's opinion, could affect study outcomes.
• Has TSC-specific tumor growth which, in the investigator's opinion, could affect the effectiveness endpoints.
• Has previously undergone significant surgery for epilepsy that, in the investigator's opinion, may impact the assessment of outcomes.
• Has initiated felbamate within the last 12 months prior to Screening.
• 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.
• Has received an investigational medicinal product within the 3 months prior to the Screening Visit.
• Has previously been assigned study intervention for this study or is currently enrolled in any other interventional study.
• Has laboratory values at the Baseline Visit that are abnormal and of clinical significance in the investigator's opinion.
• Participant has significantly impaired hepatic function at the Baseline Visit.
• 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).
• Has any known or suspected hypersensitivity to cannabinoids or any of the excipients of CBD-OS.
• Has a known or suspected history of alcohol or substance abuse.

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (19)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06519, United States

Location

University of Florida Health - Department of Neurology

Gainesville, Florida, 32608, United States

Location

Nicklaus Children's Health, Miami

Miami, Florida, 33155, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Minnesota Epilepsy Group

Roseville, Minnesota, 55113, United States

Location

Atrium Health Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Le Bonheur Children's Hospital

Memphis, Tennessee, 38103, United States

Location

University of Texas Health Science Center at Houston - Clinical Research Unit

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center - San Antonio

San Antonio, Texas, 78229, United States

Location

University of Virginia, Charlottesville

Charlottesville, Virginia, 22903, United States

Location

Alberta Children's Hospital

Calgary, Alberta, T3B 6AB, Canada

Location

BC Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

The Children's Memorial Health Institute

Warsaw, 04-736, Poland

Location

Evelina London Children's Hospital Guys St Thomas' NHS Foundation Trust, the Guy's Hospital

London, England, SE1 7EH, United Kingdom

Location

University Hospitals Bristol NHS Foundation Trust

Bristol, BS1 3NU, United Kingdom

Location

Sheffield Children's NHS Foundation Trust

Sheffield, 2TH, United Kingdom

Location

MeSH Terms

Conditions

Seizures; Tuberous Sclerosis; Behavior

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; 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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2023
• First Posted: May 18, 2023
• Study Start: June 29, 2023
• Primary Completion: April 6, 2026
• Study Completion: April 6, 2026
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

CA (3); PL (1); GB (3); US (12)