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Trial registered on ANZCTR


Registration number
ACTRN12624000948594
Ethics application status
Approved
Date submitted
1/07/2024
Date registered
5/08/2024
Date last updated
24/11/2024
Date data sharing statement initially provided
5/08/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Efficacy And Withdrawal Symptoms in Transition Between Cannabidivarin (CBDV) and Cannabidiol (CBD) in Children with Rett Syndrome and Refractory Epilepsy
Scientific title
Efficacy And Withdrawal Symptoms in Transition Between CBDV to CBD in Children with Rett Syndrome and Refractory Epilepsy
Secondary ID [1] 312430 0
Nil known
Universal Trial Number (UTN)
U1111-1310-1734
Trial acronym
Linked study record
The previous phase I trial will have the same participants for the current study. The publication of the phase I is: Hurley EN, Ellaway CJ, Johnson AM, Truong L, Gordon R, Galettis P, Martin JH, Lawson JA. Efficacy and safety of cannabidivarin treatment of epilepsy in girls with Rett syndrome: A phase 1 clinical trial. Epilepsia. 2022 Jul;63(7):1736-1747. doi: 10.1111/epi.17247. Epub 2022 Apr 20

Health condition
Health condition(s) or problem(s) studied:
Rett Syndrome 334246 0
Refractory Epilepsy 334321 0
Condition category
Condition code
Neurological 330911 330911 0 0
Epilepsy
Neurological 330980 330980 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Efficacy And Withdrawal Symptoms in Transition Between Cannabidivarin (CBDV) and Cannabidiol (CBD) in Children with Rett Syndrome and Refractory Epilepsy
Treatment regime (oral dosing):
Day 0-7: CBDV 7.5mg/kg/day and CBD 2.5mg/kg/day
Day 8-14: CBDV 5mg/kg/day and CBD 5mg/kg/day
Day 15-21: CBDV 2.5mg/kg/day and CBD 7.5mg/kg/day
Day 22-28: CBDV 0mg/kg/day and CBD 10mg/kg/day
onward: CBD 10-20mg/kg/day depending on response from patient.
Adherence: weight of returned CBD/CBDV bottle.


Intervention code [1] 328936 0
Treatment: Drugs
Comparator / control treatment
(1) baseline on CBDV (4 week screening period). The screening period will have patents record prospective seizures in the seizure diary.
Control group
Active

Outcomes
Primary outcome [1] 338674 0
Seizure Frequency
Timepoint [1] 338674 0
13 weeks, 1 year (primary), 3 years post transition commencement.
Secondary outcome [1] 436976 0
global impression of change
Timepoint [1] 436976 0
1 year post-transition commencement
Secondary outcome [2] 436977 0
CBD withdrawal symptoms
Timepoint [2] 436977 0
13 weeks post-transition commencement
Secondary outcome [3] 436978 0
Sleep
Timepoint [3] 436978 0
13 weeks post-transition commencement

Eligibility
Key inclusion criteria
1. Involvement in previous phase I trial of CBDV in Rett Syndrome.
2. Rett syndrome with known MECP2 mutation.
3. Refractory epilepsy (having failed an adequate trial of at least two standard anti-seizure medications).
4. Patient and caregiver willing and able to comply with all trial requirements.
5. All medications and interventions stable for four weeks prior to screening and patient / caregiver willing to maintain stable regimen throughout trial.
Minimum age
12 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Another significant neurological diagnosis (history of traumatic brain injury, metabolic disease, or infection).
2. Significant non-neurological diagnosis (e.g., severe cardiac or respiratory disease).
3. Pre-existing abnormalities of full blood count, electrolytes, coagulation, hepatic function or enzymes considered clinically significant as judged by the investigator (e.g., WCC < 4, platelets < 60 000, ANC < 1, ALT or AST > 2 times upper limit normal).
4. Clinically significant ECG abnormality (e.g., QTc > 460 msec, PR > 0.2 sec).
5. Patient currently using or has used other cannabinoid products other than CBDV and unwilling to abstain for duration of the trial.
6. Female subjects who are pregnant will be excluded. A negative serum pregnancy test is required at screening. If female subjects become pregnant during the study, they must inform the investigator, and consult an obstetrician.
7. Known allergy to or any component of either CBDV, CBD or any cannabinoid.
8. Patient has any other significant disease or disorder which in the opinion of the investigator, may put the patient at risk or influence the result of the trial or the patient’s ability to participate in the trial.
9. Any abnormalities identified following a physical examination of the patient that, in the opinion of the investigator, would jeopardize the safety of the patient if they took part in the trial.
10. Patient is taking more than four other concurrent anti-epileptic drugs.
11. Patient has taken felbamate in year prior to screening.

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 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
12/08/2024
Actual
21/08/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
3
Accrual to date
3
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 26745 0
Sydney Children's Hospital - Randwick
Recruitment postcode(s) [1] 42792 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 316847 0
Commercial sector/Industry
Name [1] 316847 0
Jazz Pharmaceuticals
Country [1] 316847 0
Australia
Primary sponsor type
Hospital
Name
Sydney Children's Hospital Network
Address
Country
Australia
Secondary sponsor category [1] 319081 0
None
Name [1] 319081 0
Address [1] 319081 0
Country [1] 319081 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315610 0
Sydney Children's Hospitals Network Human Research Ethics Committee
Ethics committee address [1] 315610 0
http://www.schn.health.nsw.gov.au/health-professionals/our-research/ethics-research-governance
Ethics committee country [1] 315610 0
Australia
Date submitted for ethics approval [1] 315610 0
Approval date [1] 315610 0
06/06/2023
Ethics approval number [1] 315610 0
2023/ETH00474

Summary
Brief summary
All the patients with Rett Syndrome, previously on CBDV as part of the phase I trial, will be offered transition to Epidyolex, with monitoring for change in seizure frequency and severity, sleep behaviours and emergence of withdrawal symptoms. The study hypothesis is that patients with refractory epilepsy and Rett syndrome will respond to CBD (similar seizure frequency, seizure severity) when transitioned from CBDV.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 135242 0
Dr Alexandra Johnson
Address 135242 0
Sydney Children's Hospital, High St, Randwick NSW 2031
Country 135242 0
Australia
Phone 135242 0
+612 9382 1547
Fax 135242 0
Email 135242 0
[email protected]
Contact person for public queries
Name 135243 0
Kaitlyn Griffin
Address 135243 0
Sydney Children's Hospital, High St, Randwick NSW 2031
Country 135243 0
Australia
Phone 135243 0
+612 9382 5376
Fax 135243 0
Email 135243 0
[email protected]
Contact person for scientific queries
Name 135244 0
Kaitlyn Griffin
Address 135244 0
Sydney Children's Hospital, High St, Randwick NSW 2031
Country 135244 0
Australia
Phone 135244 0
+612 9382 5376
Fax 135244 0
Email 135244 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
Pooled deidentified results will be released post analysis upon publication (if applicable).


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.