Trial Outcomes & Findings for Cannabidiol Expanded Access Study in Medically Refractory Sturge-Weber Syndrome (NCT NCT02332655)

Last Updated: 2022-03-02

Results Overview

A baseline seizure frequency was recorded for each subject in a diary for eight weeks prior to investigational drug initiation and parents/caregivers documented seizures on a daily basis throughout the trial using a seizure log. For assessing the efficacy of CBD, the investigator counted the change in frequency of seizures per month. The number of seizures within 56 days of the baseline and the number of seizures within 56 days of week 14 were calculated. Higher seizure frequency indicates worse outcome. This outcome is measured as the change in number of seizures per month between the baseline and week 14 time points.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

5 participants

Primary outcome timeframe

Measured within 56 days before baseline and 56 days before week 14

Results posted on

2022-03-02

Participant Flow

All enrolled participants will receive cannabidiol.

Participant milestones

Participant milestones
Measure	Cannabidiol All subjects will receive the experimental Epidiolex (cannabidiol) oral solution to be taken at home twice a day, and will be treated on an outpatient basis. The drug will be taken for 48 weeks unless the subject chooses to participate in the extension phase of the study, in which case the subject will continue to receive the drug for one additional year or until the drug is approved for clinical use for the treatment of epilepsy in patients with Sturge-Weber syndrome. Cannabidiol: Initiation of treatment will begin with 2mg/kg/day. The dose will be increased by 3 mg/kg/day after seven days and then by 5 mg/kg/day every seven days up to a maximum dose of 25 mg/kg/day given. The dose of concomitant antiepileptic drugs will remain unchanged during the first 12 weeks of CBD treatment (or until 8 weeks after steady state at final dose), unless symptoms of toxicity and/or significant changes in blood levels are observed.
Overall Study STARTED	5
Overall Study COMPLETED	4
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Cannabidiol All subjects will receive the experimental Epidiolex (cannabidiol) oral solution to be taken at home twice a day, and will be treated on an outpatient basis. The drug will be taken for 48 weeks unless the subject chooses to participate in the extension phase of the study, in which case the subject will continue to receive the drug for one additional year or until the drug is approved for clinical use for the treatment of epilepsy in patients with Sturge-Weber syndrome. Cannabidiol: Initiation of treatment will begin with 2mg/kg/day. The dose will be increased by 3 mg/kg/day after seven days and then by 5 mg/kg/day every seven days up to a maximum dose of 25 mg/kg/day given. The dose of concomitant antiepileptic drugs will remain unchanged during the first 12 weeks of CBD treatment (or until 8 weeks after steady state at final dose), unless symptoms of toxicity and/or significant changes in blood levels are observed.
Overall Study Lack of Efficacy	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cannabidiol n=5 Participants All subjects will receive the experimental Epidiolex (cannabidiol) oral solution to be taken at home twice a day, and will be treated on an outpatient basis. The drug will be taken for 48 weeks unless the subject chooses to participate in the extension phase of the study, in which case the subject will continue to receive the drug for one additional year or until the drug is approved for clinical use for the treatment of epilepsy in patients with Sturge-Weber syndrome. Cannabidiol: Initiation of treatment will begin with 2mg/kg/day. The dose will be increased by 3 mg/kg/day after seven days and then by 5 mg/kg/day every seven days up to a maximum dose of 25 mg/kg/day given. The dose of concomitant antiepileptic drugs will remain unchanged during the first 12 weeks of CBD treatment (or until 8 weeks after steady state at final dose), unless symptoms of toxicity and/or significant changes in blood levels are observed.
Age, Categorical <=18 years	4 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	8.83 years STANDARD_DEVIATION 6.3 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Region of Enrollment United States	5 participants n=5 Participants

PRIMARY outcome

Timeframe: Measured within 56 days before baseline and 56 days before week 14

Population: 4 out of 5 subjects were included in analysis as subject 5 was removed early (before week 14) due to lack of efficacy and adverse events.

Outcome measures

Outcome measures
Measure	Cannabidiol n=4 Participants All subjects will receive the experimental Epidiolex (cannabidiol) oral solution to be taken at home twice a day, and will be treated on an outpatient basis. The drug will be taken for 48 weeks unless the subject chooses to participate in the extension phase of the study, in which case the subject will continue to receive the drug for one additional year or until the drug is approved for clinical use for the treatment of epilepsy in patients with Sturge-Weber syndrome. Cannabidiol: Initiation of treatment will begin with 2mg/kg/day. The dose will be increased by 3 mg/kg/day after seven days and then by 5 mg/kg/day every seven days up to a maximum dose of 25 mg/kg/day given. The dose of concomitant antiepileptic drugs will remain unchanged during the first 12 weeks of CBD treatment (or until 8 weeks after steady state at final dose), unless symptoms of toxicity and/or significant changes in blood levels are observed.
Number of Seizures Per Month Subject 1 Overall Average Number of Seizures per Month at Baseline	33.5 Seizures per month Standard Deviation 7.78
Number of Seizures Per Month Subject 1 Overall Average Number of Seizures per Month at Week 14	30.0 Seizures per month Standard Deviation 2.83
Number of Seizures Per Month Subject 2 Overall Average Number of Seizures per Month at Baseline	3.0 Seizures per month Standard Deviation 1.41
Number of Seizures Per Month Subject 2 Overall Average Number of Seizures per Month at Week 14	0.5 Seizures per month Standard Deviation 0.71
Number of Seizures Per Month Subject 3 (Re-enrolled) Overall Average Number of Seizures per Month at Baseline	3.0 Seizures per month Standard Deviation 1.41
Number of Seizures Per Month Subject 3 (Re-enrolled) Overall Average Number of Seizures per Month at Week 14	2.0 Seizures per month Standard Deviation 0.00
Number of Seizures Per Month Subject 4 Overall Average Number of Seizures per Month at Baseline	5.0 Seizures per month Standard Deviation 1.41
Number of Seizures Per Month Subject 4 Overall Average Number of Seizures per Month at Week 14	0.5 Seizures per month Standard Deviation 0.71
Number of Seizures Per Month Subject 5 Overall Average Number of Seizures per Month at Baseline	1.0 Seizures per month Standard Deviation 0.00

SECONDARY outcome

Timeframe: Measured at Baseline and most recent visit within 1 year

Population: 4 out of 5 subjects were included in analysis as subject 5 was removed early due to lack of efficacy. Data were not collected for Subject 5 as the subject was removed at week 9 due to lack of efficacy.

The percentage change, between the seizure frequency per month reported at baseline compared to seizure frequency per month at the subject's most recent visit, on CBD was calculated. Higher positive percentage change in seizure frequency per month would indicate better outcome. Positive values indicate a decrease in seizure frequency.

Outcome measures

Outcome measures
Measure	Cannabidiol n=4 Participants All subjects will receive the experimental Epidiolex (cannabidiol) oral solution to be taken at home twice a day, and will be treated on an outpatient basis. The drug will be taken for 48 weeks unless the subject chooses to participate in the extension phase of the study, in which case the subject will continue to receive the drug for one additional year or until the drug is approved for clinical use for the treatment of epilepsy in patients with Sturge-Weber syndrome. Cannabidiol: Initiation of treatment will begin with 2mg/kg/day. The dose will be increased by 3 mg/kg/day after seven days and then by 5 mg/kg/day every seven days up to a maximum dose of 25 mg/kg/day given. The dose of concomitant antiepileptic drugs will remain unchanged during the first 12 weeks of CBD treatment (or until 8 weeks after steady state at final dose), unless symptoms of toxicity and/or significant changes in blood levels are observed.
Percentage Change in Seizure Frequency at Most Recent Visit on CBD Compared With Baseline Subject 1 Percent decrease in Seizure Frequency at Most Recent Visit on CBD Compared with Baseline	12 Percentage Change in Seizure Frequency
Percentage Change in Seizure Frequency at Most Recent Visit on CBD Compared With Baseline Subject 2 Percent decrease in Seizure Frequency at Most Recent Visit on CBD Compared with Baseline	100 Percentage Change in Seizure Frequency
Percentage Change in Seizure Frequency at Most Recent Visit on CBD Compared With Baseline Subject 3 Percent decrease in Seizure Frequency at Most Recent Visit on CBD Compared with Baseline	83 Percentage Change in Seizure Frequency
Percentage Change in Seizure Frequency at Most Recent Visit on CBD Compared With Baseline Subject 4 Percent decrease in Seizure Frequency at Most Recent Visit on CBD Compared with Baseline	64 Percentage Change in Seizure Frequency

Adverse Events

Cannabidiol

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cannabidiol n=5 participants at risk All subjects will receive the experimental Epidiolex (cannabidiol) oral solution to be taken at home twice a day, and will be treated on an outpatient basis. The drug will be taken for 48 weeks unless the subject chooses to participate in the extension phase of the study, in which case the subject will continue to receive the drug for one additional year or until the drug is approved for clinical use for the treatment of epilepsy in patients with Sturge-Weber syndrome. Cannabidiol: Initiation of treatment will begin with 2mg/kg/day. The dose will be increased by 3 mg/kg/day after seven days and then by 5 mg/kg/day every seven days up to a maximum dose of 25 mg/kg/day given. The dose of concomitant antiepileptic drugs will remain unchanged during the first 12 weeks of CBD treatment (or until 8 weeks after steady state at final dose), unless symptoms of toxicity and/or significant changes in blood levels are observed.
Eye disorders Left Eye Vertical Nystagmus	20.0% 1/5 • Number of events 1 • 48 weeks All adverse events, unanticipated problems, protocol deviations or other concerns will be promptly reported to the principal or co-investigator who will have primary responsibility for notifying the IRB and the KKI Office of Research Compliance. As stated previously, no serious risks are anticipated. All side effects or adverse events problems of a medical nature will also be reported to GW Pharmaceutical.
Respiratory, thoracic and mediastinal disorders Pneumonia	20.0% 1/5 • Number of events 1 • 48 weeks All adverse events, unanticipated problems, protocol deviations or other concerns will be promptly reported to the principal or co-investigator who will have primary responsibility for notifying the IRB and the KKI Office of Research Compliance. As stated previously, no serious risks are anticipated. All side effects or adverse events problems of a medical nature will also be reported to GW Pharmaceutical.
Skin and subcutaneous tissue disorders Facial Skin Infection	20.0% 1/5 • Number of events 1 • 48 weeks All adverse events, unanticipated problems, protocol deviations or other concerns will be promptly reported to the principal or co-investigator who will have primary responsibility for notifying the IRB and the KKI Office of Research Compliance. As stated previously, no serious risks are anticipated. All side effects or adverse events problems of a medical nature will also be reported to GW Pharmaceutical.

Other adverse events

Other adverse events
Measure	Cannabidiol n=5 participants at risk All subjects will receive the experimental Epidiolex (cannabidiol) oral solution to be taken at home twice a day, and will be treated on an outpatient basis. The drug will be taken for 48 weeks unless the subject chooses to participate in the extension phase of the study, in which case the subject will continue to receive the drug for one additional year or until the drug is approved for clinical use for the treatment of epilepsy in patients with Sturge-Weber syndrome. Cannabidiol: Initiation of treatment will begin with 2mg/kg/day. The dose will be increased by 3 mg/kg/day after seven days and then by 5 mg/kg/day every seven days up to a maximum dose of 25 mg/kg/day given. The dose of concomitant antiepileptic drugs will remain unchanged during the first 12 weeks of CBD treatment (or until 8 weeks after steady state at final dose), unless symptoms of toxicity and/or significant changes in blood levels are observed.
Nervous system disorders Temporary increased seizures	60.0% 3/5 • Number of events 3 • 48 weeks All adverse events, unanticipated problems, protocol deviations or other concerns will be promptly reported to the principal or co-investigator who will have primary responsibility for notifying the IRB and the KKI Office of Research Compliance. As stated previously, no serious risks are anticipated. All side effects or adverse events problems of a medical nature will also be reported to GW Pharmaceutical.
Psychiatric disorders Behavioral Issues	40.0% 2/5 • Number of events 2 • 48 weeks All adverse events, unanticipated problems, protocol deviations or other concerns will be promptly reported to the principal or co-investigator who will have primary responsibility for notifying the IRB and the KKI Office of Research Compliance. As stated previously, no serious risks are anticipated. All side effects or adverse events problems of a medical nature will also be reported to GW Pharmaceutical.
Investigations Increased aspartate aminotransferase liver function test	20.0% 1/5 • Number of events 1 • 48 weeks All adverse events, unanticipated problems, protocol deviations or other concerns will be promptly reported to the principal or co-investigator who will have primary responsibility for notifying the IRB and the KKI Office of Research Compliance. As stated previously, no serious risks are anticipated. All side effects or adverse events problems of a medical nature will also be reported to GW Pharmaceutical.
Eye disorders Right eye exotropia and redness/intermittent exotropia without redness	20.0% 1/5 • Number of events 1 • 48 weeks All adverse events, unanticipated problems, protocol deviations or other concerns will be promptly reported to the principal or co-investigator who will have primary responsibility for notifying the IRB and the KKI Office of Research Compliance. As stated previously, no serious risks are anticipated. All side effects or adverse events problems of a medical nature will also be reported to GW Pharmaceutical.
General disorders Tiredness	20.0% 1/5 • Number of events 1 • 48 weeks All adverse events, unanticipated problems, protocol deviations or other concerns will be promptly reported to the principal or co-investigator who will have primary responsibility for notifying the IRB and the KKI Office of Research Compliance. As stated previously, no serious risks are anticipated. All side effects or adverse events problems of a medical nature will also be reported to GW Pharmaceutical.

Additional Information

Dr. Anne Comi

Kennedy Krieger Institute

Phone: 4439239172

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place