Clinical trial NCT05864846: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
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
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-05-18
Enrollment: 79
Sex: ALL
Minimum age (years): 1
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in the most problematic behavior Numerical Rating Score (NRS) score within the TAND-SQ
timeFrame: Baseline, Week 13, Week 26, Week 52
measure: Change in Tuberous Sclerosis Complex Associated Neuropsychiatric Disorders Self-report, Quantified Checklist (TAND-SQ) score
timeFrame: Baseline, Week 13, Week 26, Week 52
measure: Change in Aberrant Behavior Checklist (ABC) score
timeFrame: Baseline, Week 13, Week 26, Week 52
measure: Change in Child Behavior Checklist (CBCL) score
timeFrame: Baseline, Week 26, Week 52
measure: Change in Adult Behavior Checklist (ABCL) score
timeFrame: Baseline, Week 26, Week 52
measure: Change in Adult Self-Report (ASR) score
timeFrame: Baseline, Week 26, Week 52
measure: Change in Patient-Reported Outcomes Measurement Information System (PROMIS) domains score
timeFrame: Baseline, Week 26, Week 52
measure: Change in sleep characteristics using the Children's Sleep Habits Questionnaire (CSHQ)
timeFrame: Baseline, Week 26
measure: Change in sleep characteristics using the Pittsburgh Sleep Quality Index (PSQI)
timeFrame: Baseline, Week 26
measure: Change in executive function using Behavior Rating Inventory of Executive Function (BRIEF)
timeFrame: Baseline, Week 26
measure: Change in caregiver-reported assessment of Quality of Life (QOL) using Pediatric Quality of Life Survey Family Impact Module (PedsQL FIM)
timeFrame: Baseline, Week 26
measure: Change in caregiver-reported assessment of family functioning using Pediatric Quality of Life Survey Family Impact Module (PedsQL FIM)
timeFrame: Baseline, Week 26
measure: Change in assessment of QOL using Pediatric Quality of Life Inventory (PedsQL)
timeFrame: Baseline, Week 26
measure: Change in caregiver impression of overall severity of symptoms (behavior and seizure control) using the Caregiver Global Impression of Severity (CareGI-S)
timeFrame: Baseline, Week 4, Week 13, Week 26, Week 52
measure: Change in participant impression of overall severity of symptoms (behavior and seizure control) using the Patient Global Impression of Severity (PGI-S)
timeFrame: Baseline, Week 4, Week 13, Week 26, Week 52
measure: Change in clinician impression of overall severity of symptoms (behavior and seizure control) using the Clinician Global Impression of Severity (CGI-S)
timeFrame: Baseline, Week 4, Week 13, Week 26, Week 52
measure: Retention Rate
timeFrame: Baseline, Week 13, Week 26, Week 52
measure: Number of participants considered treatment responders
timeFrame: Baseline, Week 4, Week 13, Week 26, Week 52
measure: Change in number of seizure-free days
timeFrame: Baseline, Week 4, Week 13, Week 26, Week 52
measure: Number of participants experiencing a worsening, no change, or improvement in seizure frequency
timeFrame: Baseline, Week 4, Week 13, Week 26, Week 52
measure: Change in ideation score per the Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline, Week 4, Week 13, Week 26, Week 52
measure: Change in number of suicide attempts per the C-SSRS
timeFrame: Baseline, Week 4, Week 13, Week 26, Week 52
measure: Change in ideation score per the Children's C-SSRS
timeFrame: Baseline, Week 4, Week 13, Week 26, Week 52
measure: Change in number of suicide attempts per the Children's C-SSRS
timeFrame: Baseline, Week 4, Week 13, Week 26, Week 52
measure: Number of participant inpatient hospitalizations due to epilepsy
timeFrame: Up to Week 52
measure: Number of withdrawals due to Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to Week 52
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida Health - Department of Neurology
state: Florida
city: Miami
country: United States
facility: Nicklaus Children's Health, Miami
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Roseville
country: United States
facility: Minnesota Epilepsy Group
state: Minnesota
city: Winston-Salem
country: United States
facility: Atrium Health Wake Forest Baptist Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania - Penn Epilepsy Center
state: Pennsylvania
city: Memphis
country: United States
facility: Le Bonheur Children's Hospital
state: Tennessee
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston - Clinical Research Unit
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center - San Antonio
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia, Charlottesville
state: Virginia
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Vancouver
country: Canada
facility: BC Children's Hospital
state: British Columbia
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Warszawa
country: Poland
facility: The Children's Memorial Health Institute
city: London
country: United Kingdom
facility: Evelina London Children's Hospital Guys St Thomas' NHS Foundation Trust, the Guy's Hospital
state: England
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust
city: Sheffield
country: United Kingdom
facility: Sheffield Children's NHS Foundation Trust
Study officials:
References: