Lennox-Gastaut Syndrome
Conditions
Keywords
LGS, Cannabidiol, CBD-OS, Epidiolex, Epidyolex
Brief summary
This is a Phase 3b/Phase 4 study. The purpose of this study is to learn more about the efficacy of using CBD-OS as an add-on therapy for the treatment of LGS in adults.
Interventions
100 mg/ml Cannabidiol Oral solution (CBD-OS)
Sponsors
Jazz Pharmaceuticals
Jazz Pharmaceuticals Research UK Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Has a confirmed clinical diagnosis of LGS with a history of seizures and actively experiencing seizures within 6 months of screening. 2. Is naïve to CBD-OS treatment or has been off CBD-OS treatment for at least 3 months prior to screening. 3. Is willing to maintain any factors expected to affect seizures (eg, alcohol consumption, smoking, concomitant medication usage) stable for the duration of the study. 4. Is currently treated with at least 1 ASM, but no more than 3 ASMs, and is on a stable regimen for at least 4 weeks prior to screening. 5. Adequate contraceptive precautions 6. Participant has a primary caregiver/legally authorized representative (LAR) who is willing and able, in the investigator's opinion, to participate throughout the duration of the study and to comply with all study requirements 7. Experienced at least 4 or more countable major motor seizures (isolated seizures or seizures occurring in a cluster) during the 5-week Baseline Period preceding treatment. 8. Caregiver completed at least 80% of seizure diary entries during the Baseline Period with no more than 3 consecutive days of missing entries.
Exclusion criteria
1. Has a significant psychiatric illness 2. Has an illness during the 4 weeks prior to screening other than epilepsy which, in the investigator's opinion, could affect study outcomes or seizure frequency. 3. Has history of SE in the 3 months prior to screening. 4. Has any other significant disease other than epilepsy, which, in the investigator's opinion, 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. 5. Has previously undergone significant surgery for epilepsy in the 6 months prior to screening or planned to undergo surgery for epilepsy during the study. 6. Is currently using or has in the past used recreational or medicinal cannabis or synthetic cannabinoid-based medications, products, or supplements within the 3 months prior to screening and is not willing to undergo a 1-month washout period before being rescreened. 7. Has initiated felbamate within the 12 months prior to screening. 8. Is not willing to adjust dosage of CBD-OS if needed when using strong inducers of CYP3A4 and/or strong inducers of CYP2C19 concomitantly with CBD-OS 9. Previously discontinued cannabidiol due to severe adverse events (SAE), hypersensitivity or lack of efficacy 10. Has clinically significant abnormal lab values 11. Has clinically impaired hepatic or renal function 12. History of, current risk or presence of actual suicidal ideations 13. Has any known or suspected hypersensitivity to cannabinoids or any of the excipients of CBD-OS, such as sesame oil. 14. Has a known or suspected history of alcohol or substance abuse disorder 15. Is currently consuming, and unwilling to stop consumption, or planning to consume tonic water on a regular basis throughout the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of participants reporting 50% or more reduction in their 28-day average countable major motor seizure frequency | End of Treatment Period, Week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Retention Rate | At Weeks 8, 12, 16 and 24 | Retention Rate is defined as percentage of participants completing or continuing CBD-OS treatment at different timepoints in the study |
| Percentage of participants experiencing worsening, change, no change or improvement in in their 28-day average countable major motor and total seizure frequency | Baseline to Week 4, Baseline to Week 8, Baseline to Week 12, Baseline to Week 16, Baseline to Week 24 | As reported in participants' electronic diaries |
| Percentage of participants considered treatment responders | Baseline to Week 4, Baseline to Week 8, Baseline to Week 12, Baseline to Week 16, Baseline to Week 24 | Treatment responders will be categorized as those experiencing a 50% or more reduction, a 75% or more reduction or 100% reduction in their 28-day average seizure frequency as reported in participants' electronic diaries |
| Change in 28-day average frequency of countable major motor and total seizures | Baseline to Week 4, Baseline to Week 8, Baseline to Week 12, Baseline to Week 16, Baseline to Week 24 | Assessed per 28 days from electronic diary entries |
| Change in number of seizure-free days | Baseline to Week 4, Baseline to Week 8, Baseline to Week 12, Baseline to Week 16, Baseline to Week 24 | Assessed per 28 days from electronic diary entries |
| Change in CaGI-S severity of seizure scores | Baseline to Week 16, Baseline to Week 24 | Caregiver Global Impression of Severity (CaGI-S) is a single-item, 5-point Likert-type rating scale (ranging from 0 "not severe at all" to 5 "very severe"). Using this scale, caregivers will be asked to rate their impression of the participant's severity of seizures, and the severity of the impact caused by the seizure. |
| Change in CaGI-S severity of impact of seizures scores | Baseline to Week 16, Baseline to Week 24 | Caregiver Global Impression of Severity (CaGI-S) is a single-item, 5-point Likert-type rating scale (ranging from 0 "not severe at all" to 5 "very severe"). Using this scale, caregivers will be asked to rate their impression of the participant's severity of the impact caused by the seizure. |
| Change in VAS scores | Baseline to Week 16, Baseline to Week 24 | Visual Analog Scale (VAS) is a caregiver-reported tool used to quantify the severity of impact of subjective non-seizure symptoms and assesses sleep, communication, and disruptive behavior. The VAS enables sensitive detection of changes in non-seizure domains (disruptive behavior, Sleep, and Communication) important to patients with LGS and their caregivers. The VAS has a total score ranging from 0 to 100 with the higher score indicating worse conditions. |
| Change in CaGI-S severity of level of alertness scores | Baseline to Week 16, Baseline to Week 24 | CaGI-S Alertness is a caregiver single item assessment on a 5-point Likert-type rating scale (ranging from 0 "not severe at all" to 5 "very severe") assessing their impression of participant's severity of level of awareness |
| Change in CaGI-S severity of overall condition scores | Baseline to Week 16, Baseline to Week 24 | CaGI-S Overall Condition is a caregiver single item assessment on a 5-point Likert-type rating scale (ranging from 0 "not severe at all" to 5 "very severe") assessing their impression of participant's severity of overall condition |
| CaGI-C level of alertness scores | At Week 16, at week 24 | Caregiver Global Impression of Change (CaGI-C) Alertness is a caregiver single item assessment on a 7-point Likert-type rating scale (ranging from 1 "very much improved" to 7 "very severe") assessing their impression of participant's severity of level of awareness |
| CaGI-C overall condition scores | At Week 16, at week 24 | Caregiver Global Impression of Change (CaGI-C) overall condition is a caregiver single item assessment on a 7-point Likert-type rating scale (ranging from 1 "very much improved" to 7 "very severe") assessing their impression of participant's severity of overall condition |
| Change in CGI-S overall condition scores | Baseline to Week 16, Baseline to Week 24 | Clinician Global Impression of severity (CGI-S) Overall Condition is a clinician single item assessment on a 5-point Likert-type rating scale (ranging from 1 "not severe at all" to 5 "very severe") assessing their impression of participant's severity of level of overall condition |
| CGI-C overall condition scores | At Week 16, At Week 24 | Clinician Global Impression of Change (CGI-C) Overall Condition is a clinician single item assessment on a 7-point Likert-type rating scale (ranging from 1 "very much improved" to 5 "very much worse") assessing their impression of participant's change of overall condition |
| Change in ELDQOL Behavior subscale scores | Baseline to Week 16, Baseline to Week 24 | Epilepsy and Learning Disabilities Quality of Life (ELDQOL) is designed for the caregiver to rate the quality of life (QOL) in children with severe epilepsy and learning disabilities over the last month. The questionnaire has a total of 28 main questions, grouped into 4 subscales: behavior, seizure severity, mood, and side effects. The ELDQOL behavior subscale includes 9 of the 28 total main questions with a total score ranging from 9 to 36 with the higher score indicating greater behavioral problems |
| Change in ELDQOL seizure severity subscale scores | Baseline to Week 16, Baseline to Week 24 | Epilepsy and Learning Disabilities Quality of Life (ELDQOL) is designed for the caregiver to rate the quality of life (QOL) in children with severe epilepsy and learning disabilities over the last month. The questionnaire has a total of 28 main questions, grouped into 4 subscales: behavior, seizure severity, mood, and side effects. The ELDQOL seizure severity subscale includes 14 of the 28 total main questions with a total score ranging from 10 to 56 with the higher score indicating greater seizure severity |
| Change in ELDQOL mood scale subscale scores | Baseline to Week 16, Baseline to Week 24 | Epilepsy and Learning Disabilities Quality of Life (ELDQOL) is designed for the caregiver to rate the quality of life (QOL) in children with severe epilepsy and learning disabilities over the last month. The questionnaire has a total of 28 main questions, grouped into 4 subscales: behavior, seizure severity, mood, and side effects. The ELDQOL mood scale subscale includes 1 of the 28 total questions with a total score ranging from 16 to 64 with the higher score indicating greater mood problems |
| Change in ELDQOL side-effects profile subscale scores | Baseline to Week 16, Baseline to Week 24 | Epilepsy and Learning Disabilities Quality of Life (ELDQOL) is designed for the caregiver to rate the quality of life (QOL) in children with severe epilepsy and learning disabilities over the last month. The questionnaire has a total of 28 main questions, grouped into 4 subscales: behavior, seizure severity, mood, and side effects. The ELDQOL side-effects profile subscale includes 2 of the 28 total main questions with a score ranging from 19 to 76 with the higher score indicating greater side effects |
| Number of participants reporting adverse events leading to discontinuation | Up to week 24 | — |
| Time the adverse events started from baseline | Up to week 24 | — |
| Number of Participants with Abnormal Laboratory Values | Up to week 24 | — |
| Change in suicidal ideation scores | Baseline, up to week 24 | As evaluated by the Columbia-Suicide Severity Rating Scale (C-SSRS). The questionnaire has a total score ranging from 0 to 5 with a score of 0 indicating no suicidal ideation is present. |
| Change in number of suicide attempts | Baseline, up to week 24 | As per the response in the C-SSRS |
| Percentage of participants requiring inpatient hospitalization due to epilepsy | Up to week 24 | — |
| Change in number of usage of rescue medication | Baseline, Up to week 24 | — |
Countries
United States
Contacts
CONTACTClinical Trial Disclosure & Transparency
Outcome results
None listed