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Trial registered on ANZCTR


Registration number
ACTRN12624000888561
Ethics application status
Approved
Date submitted
3/07/2024
Date registered
22/07/2024
Date last updated
22/07/2024
Date data sharing statement initially provided
22/07/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Cannabidiol on beyond-Seizure outcomes in children and adults with Developmental and Epileptic Encephalopathy
Scientific title
A pilot study to investigate the effect of Cannabidiol on quality of life and beyond-seizure outcomes in children and adults with Developmental and Epileptic Encephalopathy
Secondary ID [1] 311112 0
Nil known
Universal Trial Number (UTN)
Trial acronym
BEYOND
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epilepsy 332280 0
Condition category
Condition code
Neurological 328994 328994 0 0
Epilepsy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is an open-labelled trial to assess the health outcomes of Cannabidiol (CBD) administered as Epidiolex. Epidiolex is a purified cannabidiol oral solution that will be administered orally or via gastrostomy and nasogastric feeding tubes.

All participants will undergo a screening process. Eligible participants will begin 48 weeks of treatment with CBD. Each treatment block includes 2 weeks of titration, 46 weeks on the maintenance dose and 10 days of drug tapering.

Treatment group A (Epidiolex)
Parents/caregivers or patients will administer the study drug orally/via gastrostomy/via a nasogastric tube in two divided doses (12 hours +/- 2 hours) daily. Dosage will be titrated over 2 weeks until the maximum (20 mg/kg/day) or best tolerated dose is reached. The maximum or best-tolerated dose will be maintained for 46 weeks.

Dosing schedule:
Day 1: 1.25 mg/kg/day via two divided doses
Day 2: 2.5mg/kg/day via two divided doses
Day 3: 5mg/kg/day via two divided doses
Day 4: 5mg/kg/day via two divided doses
Day 5: 7.5 mg/kg/day via two divided doses
Day 6: 7.5 mg/kg/day via two divided doses
Day 7: 10mg/kg/day via two divided doses
Day 8: 10mg/kg/day via two divided doses
Day 9: 15mg/kg/day via two divided doses
Day 10: 15mg/kg/day via two divided doses
Day 11: 20 mg/kg/day via two divided doses
Day 12: 20 mg/kg/day via two divided doses
Day 13: 20 mg/kg/day via two divided doses
Day 14: 20 mg/kg/day via two divided doses

Compliance with study medication will be reviewed at each virtual or in-clinic appointment. Pharmacy staff will calculate the expected number of bottles (based on participants weight and expected titration schedule) required between visit time points and dispense to the participants accordingly via Direct To Patient service. Home nurses will be required to account all used and/or any unused bottles of medication and report to the study site pharmacy where clinical trial pharmacists will complete accountability and adherence calculations. This information will be forwarded to the PI for noting.

A new prescription for the study medication will be provided by the PI to the clinical trial pharmacists who will dispense a new supply of study medication to see participants through until their next appointment.

Taper schedule:
Day 1: 20 mg/kg/day via two divided doses
Day 2: 17.5 mg/kg/day via two divided doses
Day 3: 15 mg/kg/day via two divided doses
Day 4:12.5 mg/kg/day via two divided doses
Day 5: 10 mg/kg/day via two divided doses
Day 6: 7.5 mg/kg/day via two divided doses
Day 7: 5 mg/kg/day via two divided doses
Day 8: 2.5 mg/kg/day via two divided doses
Day 9: 1.35 mg/kg/day via two divided doses
Day 10: 0 mg/kg/day
Intervention code [1] 327567 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 336785 0
• To assess the effect of Epidyolex ® on Quality of Life in participants with Developmental and Epileptic Encephalopathy (DEE) and their caregivers.
Timepoint [1] 336785 0
Baseline and 48 weeks post-baseline
Secondary outcome [1] 429670 0
• Determine changes in response in the global The Pittsburgh Sleep Quality Index (PSQI) score at 48 weeks compared with baseline.
Timepoint [1] 429670 0
Baseline and 48 weeks post-baseline
Secondary outcome [2] 429746 0
• Determine changes in response in the Clinical Global Impressions Scale (CGIC) and Patients' Global Impression of Change (PGIC) score at 48 weeks compared with baseline. This will be assessed as a composite outcome.
Timepoint [2] 429746 0
Baseline and 48 weeks post - baseline
Secondary outcome [3] 437073 0
• Change in degree of cognitive impairment using The Mini-Mental Examination for Children (MCC) or A Mini-Mental State Examination (MMSE) scores at 48 weeks compared with baseline. This will be assessed as a composite outcome
Timepoint [3] 437073 0
Baseline and 48 weeks post-baseline
Secondary outcome [4] 437074 0
• Change in quality of life using the 36-Item Short Form Survey (SF-36) score at 48 weeks compared with baseline.
Timepoint [4] 437074 0
Baseline and 48 weeks post-baseline
Secondary outcome [5] 437075 0
• Change in seizure management using the Epilepsy Self-Efficacy Scale-33 Items (ESES) at 48 weeks compared with baseline.
Timepoint [5] 437075 0
Baseline and 48 weeks post-baseline
Secondary outcome [6] 437076 0
• Burden of epileptic disease
Timepoint [6] 437076 0
Baseline and 48 weeks post-baseline
Secondary outcome [7] 437715 0
• Change in self esteem using the Rosenberg Self-Esteem Scale (ESS) score at 48 weeks compared with baseline.
Timepoint [7] 437715 0
Baseline and 48 weeks post-baseline

Eligibility
Key inclusion criteria
1. Has a documented clinical diagnosis of Dravet syndrome, Lennox-Gastaut syndrome as confirmed by the Pharmaceutical Benefits Scheme (PBS), or other developmental and epileptic encephalopathy ß.
2. Male or female (non-pregnant, non-lactating female) aged 2 years € to 65 years old.
3. Have countable motor seizures *, defined as:
- an average of greater than or equal to (>=) 2 per month during the past 3 months, based on the Study Doctor's assessment
- and a monthly average of >=1 per month during the Baseline Period, based on the seizure diary record, documented by caregiver report or Study Doctor medical notes.
4. Subjects can be taking 1 and no more than 3 concomitant antiseizure medications (ASMs) a. All doses must be stable for at least 4 weeks before screening and expected to be maintained throughout the study (until the end of the treatment period)
5. The Participant/parent/caregiver is able and willing to complete study visits, complete the questionnaires, record concomitant medications, and take study drugs as instructed.
6. For participants with G-tube/Percutaneous endoscopic gastrostomy (PEG) tube, G-tubes/PEG tubes should have been placed and been functioning for at least 3 months before screening.

* drop seizures, tonic-clonic, tonic, bilateral clonic, atonic, myoclonic-atonic, myoclonic-tonic-clonic, focal seizures with bilateral hyperkinetic motor features

a Epilepsy surgery is allowed and will not be counted as a concomitant ASM. A ketogenic diet is allowed and will not be counted as a concomitant ASM. The subject must be on a stable dietary regimen that produces ketosis for at least 6 weeks before screening and is expected to be maintained throughout the study.

ß CDKL5 Deficiency Disorder, SCN2A, SYNGAP1, West Syndrome, STXBP1, Ring20 Chromosome disorder, Rett Syndrome and DEPDC5.

€ The minimum age is due to the recommended age limit for using the portable electroencephalogram (EEG) device. Subjects between the ages of 2-6 years are eligible if their parent/guardian can provide an EEG completed in the last 6 months at the Baseline and the end of the trial.
Minimum age
2 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Seizures secondary to an infection, neoplasia, demyelinating disease, degenerative neurological disease, or central nervous system disease deemed progressive, metabolic illness, or progressive degenerative disease.
2. History or presence of any significant medical or surgical condition other than a DEE
3. History of jaundice which lasts longer than 1 week will require exclusion of hepatic disease before entering the study.
4. Subjects who are known to have a terminal illness.
5. Any clinically significant laboratory abnormalities or clinically significant abnormalities on pre-study physical examination, vital signs, or ECG that in the judgment of the Study Doctor indicate a medical problem that would preclude study participation.
6. Subjects who are planning to begin to follow a ketogenic or other specialized dietary therapy during the study.
7. Exposure to any other investigational drug or device within 5 half-lives or 30 days before screening (Visit 1), whichever is longer or plans to participate in another drug or device trial at any time during the study.
8. Concurrent enrolment in any other type of medical research judged by the Study Doctor not to be scientifically or medically compatible with this study.
9. Subjects using felbamate who have presented with clinically significant abnormalities and/or hepatic dysfunction during felbamate treatment, and subjects who have taken felbamate for less than 6 months before screening.
10. Subjects who are currently taking adrenocorticotropic hormone.
11. Subjects who did not tolerate Cannabidiol when taken previously or were allergic to sesame seed/oil.
12. Subjects who have a Vagal Nerve Stimulator (VNS) device. µ

µ Subjects with a VNS can be eligible if an EEG can be provided to the study doctor at the beginning and the end of the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 0
Type of endpoint/s
Efficacy
Statistical methods / analysis
Using continuous measures of QoL obtained from EQ-5D-5L, we are comparing the outcome at 48 weeks to the baseline. All analyses will be performed using SPSS version or higher (SPSS, Chicago, IL). For all other variables, descriptive analysis will be used to describe trends.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
31/07/2024
Actual
Date of last participant enrolment
Anticipated
31/12/2024
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 315370 0
Commercial sector/Industry
Name [1] 315370 0
Jazz Pharmaceuticals
Country [1] 315370 0
Australia
Primary sponsor type
Government body
Name
Hunter New England Local Health District
Address
Lookout Rd, New Lambton Heights NSW 2305
Country
Australia
Secondary sponsor category [1] 319104 0
None
Name [1] 319104 0
Address [1] 319104 0
Country [1] 319104 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314287 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 314287 0
Lookout Rd, New Lambton Heights NSW 2305
Ethics committee country [1] 314287 0
Australia
Date submitted for ethics approval [1] 314287 0
10/05/2024
Approval date [1] 314287 0
16/05/2024
Ethics approval number [1] 314287 0
EC00403
Ethics committee name [2] 314296 0
Hunter New England Human Research Ethics Committee
Ethics committee address [2] 314296 0
Lookout Rd, New Lambton Heights NSW 2305
Ethics committee country [2] 314296 0
Australia
Date submitted for ethics approval [2] 314296 0
30/04/2024
Approval date [2] 314296 0
15/05/2024
Ethics approval number [2] 314296 0

Summary
Brief summary
The BEYOND Study is a multi-centre, open-label pilot study that utilises a participant-centric clinical trial protocol for epilepsy. It aims to assess the effectiveness, safety, and tolerability of Epidyolex as an adjunctive therapy for beyond seizure outcomes in individuals aged 2 to 65 years with DEE. The study will enrol 20 participants from metropolitan and regional areas in New South Wales, including rural and remote locations. The acceptability of this model will help guide health economists and medical affairs teams in collecting cost-effective data that can be used to optimise Pharmaceutical Benefits Advisory Committee (PBAC) submissions with regulators.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 131066 0
Ms Linda Truong
Address 131066 0
Hunter New England Local Health District, Lookout Rd, New Lambton Heights NSW 2305
Country 131066 0
Australia
Phone 131066 0
+61403436888
Fax 131066 0
Email 131066 0
[email protected]
Contact person for public queries
Name 131067 0
Linda Truong
Address 131067 0
Hunter New England Local Health District, Lookout Rd, New Lambton Heights NSW 2305
Country 131067 0
Australia
Phone 131067 0
+61403436888
Fax 131067 0
Email 131067 0
[email protected]
Contact person for scientific queries
Name 131068 0
Linda Truong
Address 131068 0
Hunter New England Local Health District, Lookout Rd, New Lambton Heights NSW 2305
Country 131068 0
Australia
Phone 131068 0
+61403436888
Fax 131068 0
Email 131068 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.