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Trial registered on ANZCTR


Registration number
ACTRN12619000216112
Ethics application status
Approved
Date submitted
11/02/2019
Date registered
14/02/2019
Date last updated
23/09/2019
Date data sharing statement initially provided
14/02/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Clinical Study of Synthetic Cannabidiol in Children and Adolescents with Autism Spectrum Disorder
Scientific title
An Open-Label, Single-Center, Tolerability and Efficacy Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents with Autism Spectrum Disorder
Secondary ID [1] 297268 0
ZYN2-CL-030
Universal Trial Number (UTN)
Trial acronym
BRIGHT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pediatric Autism Spectrum Disorder
311341 0
Condition category
Condition code
Neurological 309978 309978 0 0
Other neurological disorders
Mental Health 309979 309979 0 0
Autistic spectrum disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is an open-label single-center study, to assess the safety, tolerability and efficacy of ZYN002 (a synthetic cannabidiol) administered as a transdermal gel, for the treatment of child and adolescent patients with Autism Spectrum Disorder. Approximately 36 male and female patients ages 4 to < 18 years will be treated for 14 weeks.
The study gel will be applied to clean, dry, intact skin of the shoulders and/or upper arms.
All participants will undergo a screening process to assess eligibility. Eligible participants will then participate in up to a 14 week treatment period, where all participants will received ZYN002.
Parents/caregivers will apply the study gel twice daily for the treatment period.
Participants who weigh less than or equal to 35 kg, will receive 1 sachet of ZYN002 (125 mg of cannabidiol), applied every 12 hours (± 2 hours).
Participants who weigh more than 35 kg will receive 2 sachets of ZYN002 (250 mg of cannabidiol), applied every 12 hours (± 2 hours).
Participants who are taking anti-epileptic drugs may have an additional one or two weeks of treatment to taper off study treatment.
After the final dose, patients will be followed weekly for 4 weeks by telephone, prior to discharge from the study.
Patient compliance with the intervention will be monitored by the study coordinator through drug accountability at each study visit.
Intervention code [1] 313520 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 318894 0
To evaluate the safety and tolerability of ZYN002 administered as a twice daily dose of transdermal gel formulation for 14 weeks.
Safety assessments will include collection of any adverse events, physical and neurological exams, the Columbia-Suicide Severity Rating Scale – Children’s version, clinical laboratory safety assessments (hematology, chemistry and urinalysis), vital signs and 12-lead ECGs.
As the study drug is delivered transdermally, tolerability to study drug application will be assessed through skin check examinations performed at each visit after treatment with study gel has been initiated.
Timepoint [1] 318894 0
Safety and tolerability will be assessed at every study visit from Day 1 to end of treatment, including Day 1, Weeks 6 and 14, and at any Unscheduled Visits and the taper period.
Secondary outcome [1] 366584 0
Change from Day 1 to Week 14 in the Aberrant Behavior Checklist- Community (Irritability Subscale) score
Timepoint [1] 366584 0
At Day 1, Week 6, and Week 14 (End of Study or Early Termination)
Secondary outcome [2] 366585 0
Change in the ABC-C Irritability Subscale score from Day 1 to Week 6
Timepoint [2] 366585 0
At Day 1 and Week 6
Secondary outcome [3] 366586 0
Change in ABC-C Socially Unresponsive/Lethargic Subscale scores from Day to Weeks 6 and 14.
Timepoint [3] 366586 0
At Day 1, Week 6, and Week 14 (End of Study or Early Termination)
Secondary outcome [4] 366587 0
Change in Repetitive Behavior Scale-Revised (RBS-R) from Day 1 to Weeks 6 and 14.
Timepoint [4] 366587 0
At Day 1, Week 6, and Week 14 (End of Study or Early Termination)
Secondary outcome [5] 366590 0
Change in Anxiety, Depression and Mood Scale from Day 1 to Weeks 6 and 14.
Timepoint [5] 366590 0
At Day 1, Week 6, and Week 14 (End of Study or Early Termination)
Secondary outcome [6] 366591 0
Change in the Clinical Global Impression-Improvement from Day 1 to Weeks 6 and 14
Timepoint [6] 366591 0
At Day 1, Week 6, and Week 14 (End of Study or Early Termination)
Secondary outcome [7] 366592 0
Change in Autism Parenting Stress Index from Day 1 to Weeks 6 and 14
Timepoint [7] 366592 0
At Day 1, Week 6, and Week 14 (End of Study or Early Termination)
Secondary outcome [8] 366593 0
Change in the Social Responsiveness Scale (pSRS-2; parents) from Day 1 to Weeks 6 and 14
Timepoint [8] 366593 0
At Day 1, Week 6, and Week 14 (End of Study or Early Termination)
Secondary outcome [9] 366594 0
Change in Social Responsiveness Scale (tSRS-2; teacher) from Day 1 to Week 14
Timepoint [9] 366594 0
At Day 1 and Week 14 (End of Study or Early Termination)
Secondary outcome [10] 366595 0
Change in the Sleep Clinical Global Impression from Day 1 to Week 14
Timepoint [10] 366595 0
At Day 1 and Week 14 (End of Study or Early Termination)
Secondary outcome [11] 366596 0
Change in Child Behavior Checklist (CBC-L) from Day 1 to Weeks 6 and 14
Timepoint [11] 366596 0
At Day 1, Week 6, and Week 14 (End of Study or Early Termination)
Secondary outcome [12] 366597 0
Change in Pediatric Quality of Life Inventory - Family Impact Module from Day 1 to Week 14
Timepoint [12] 366597 0
At Day 1 and Week 14 (End of Study or Early Termination)
Secondary outcome [13] 366598 0
Evaluation of CBD plasma level exposure
Timepoint [13] 366598 0
At Day 1 (pre-dose baseline sample) and Week 14/EOS/ET Visits, blood will be drawn for a trough plasma level for the determination of CBD

Eligibility
Key inclusion criteria
1. Male or female children and adolescents aged 4 to <18 years, at the time of Screening.
2. Judged by the Investigator to be in generally good health at Screening based upon the results of a medical history, physical examination, 12-lead ECG, and clinical laboratory test results.
3. Patients must have a diagnosis of ASD confirmed by DSM-5 criteria.
4. Patients have a CGI-S score of 4 or higher at Screening and Visit 2.
5. Patients must have a score on the ABC-C Irritability Subscale of 18 or higher at Screening and Visit 2.
6. Patients with a history of seizure disorders must currently be receiving treatment with a stable regimen of one or two AEDs, or must be seizure-free for one year if not currently receiving AEDs.
7. If patients are receiving non-pharmacological behavioral and/or dietary interventions, they must be stable and have been doing so for three months prior to Screening.
8. Patients have a body mass index between 12–30 kg / m2 (inclusive).
9. Females of childbearing potential must have a negative pregnancy test at the Screening Visit and a negative pregnancy test at all designated study visits.
10. Patients and parents/caregivers agree to abide by all study restrictions and comply with all study procedures.
11. Patients and parents/caregivers must be adequately informed of the nature and risks of the study and give written informed consent (and assent if applicable) prior to Screening.
12. Parents/caregiver(s) must provide written consent to assist in study drug administration.
13. In the Investigator’s opinion, patients and parents/caregivers are reliable and willing and able to comply with all protocol requirements and procedures.
Minimum age
4 Years
Maximum age
18 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Females who are pregnant, nursing, or planning a pregnancy; females of childbearing potential and male patients with a partner of childbearing potential who are unwilling or unable to use an acceptable method of contraception as outlined below for the duration of therapy and for three months after the last dose of study medication.
Standard acceptable methods of contraception include abstinence or the use of a highly effective method of contraception, including hormonal contraception, diaphragm, cervical cap, vaginal sponge, condom, vasectomy, or intrauterine device.
2. History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to any compound or chemical class related to ZYN002 or its excipients.
3. Exposure to any investigational drug or device less than or equal to 30 days prior to Screening or at any time during the study.
4. Patient has alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels greater than or equal to 2 times the upper limit of normal (ULN) or has alkaline phosphatase levels greater than or equal to 3 times the ULN as determined from Screening safety laboratories.
5. Use of cannabis or any THC or CBD-containing product within three months of Screening Visit or during the study.
6. Patient has a positive drug screen, including ethanol, cocaine, THC, barbiturates, amphetamines (unless prescribed), benzodiazepines, and opiates.
7. Patient is using the following AEDs: clobazam, phenobarbital, ethosuximide, felbamate, or vigabatrin.
8. Patient is using any strong inhibitor/inducer of CYP3A4 or sensitive substrate for CYP3A4 including but not limited to the following medications: midazolam, oral ketoconazole, fluconazole, nefazadone, rifampin, alfentanil, alfuzosin, amiodarone, cyclosporine, dasatinib, docetaxol, eplerenone, ergotamine, everolimus, fentanyl, halofantrine, irinotecan, lapatinib, levomethadyl, lumefantrine, nilotinib, pimozide, quinidine, ranolazine, sirolimus, tacrolimus, temsirolimus, toremifene, tretinioin, vincristine, vinorelbine, and St. John’s Wort.
9. Patient with diagnosis of known genetic disorder (ie. Prader-Willi Syndrome, Angelman Syndrome, Fragile X Syndrome, Rett Syndrome etc).
10. Patient has a primary psychiatric diagnosis other than ASD or anxiety, including bipolar disorder, psychosis, schizophrenia, post-traumatic stress disorder (PTSD) or major depressive disorder.
11. Patients may not be taking more than two psychoactive medications at screening or throughout the study.
12. Patient has an advanced, severe, or unstable disease that may interfere with the study outcome evaluations.
13. Patient is expected to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study.
14. Patient has an acute or progressive neurological disease, or any psychiatric disorder or severe mental abnormalities that are likely to require changes in drug therapy or interfere with the objectives of the study or ability to adhere to protocol requirements.
15. Patient has a positive result for the presence of HBsAg, HCV, or HIV antibodies.
16. Patient has known history of cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, cardiac conduction problems, exercise-related cardiac events including syncope and pre-syncope, risk factors for Torsades de pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome), or other serious cardiac problems.
17. Any clinically significant condition or abnormal findings at the Screening Visit that would, in the opinion of the Investigator, preclude study participation or interfere with the evaluation of the study medication.
18. Any skin disease or condition, including eczema, psoriasis, melanoma, acne, contact dermatitis, scarring, imperfections, lesions, tattoos, or discoloration, that may affect treatment application, application site assessments, or absorption of the study drug.
19. History of treatment for, or evidence of, drug abuse within the past year.
20. Patient responds “yes” to Question ‘4’ or ‘5’ on the C-SSRS (Children) during Screening or at any time on 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)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
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)
Safety/efficacy
Statistical methods / analysis
Descriptive statistics (mean, median, standard deviation, minimum, and maximum) for continuous data and number (n) and percentage (%) for categorical data will be presented for all efficacy and safety parameters.
All efficacy assessments will be summarized at Weeks 6 and 14.
Vital sign assessments (actual and change from screening) taken at study Day 1, Weeks 6 and 14 and will be summarized using descriptive statistics and presented by maintenance dose.
ECGs (actual and change from Screening) will be summarized by actual treatment group. ECG results including any clinically significant findings will be summarized at each study visit.
Safety laboratory and urinalysis assessments taken at Day 1, and Week 14 (actual and change from Screening) will be summarized by treatment at the time of the assessment.
Application site irritation will be summarized using counts and percentages at each respective site irritation score (0, 1, 2, 3, or 4) by dose at the time of assessment.
AEs will be tabulated by the actual treatment dose of study drug received at the time of initiation of the adverse event and classified by system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA). Additionally, AEs will be tabulated overall (total number of AEs and total number of patients with AEs).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 13065 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 25572 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 301827 0
Commercial sector/Industry
Name [1] 301827 0
Zynerba Pharmaceuticals Pty Ltd
Address [1] 301827 0
2 Riverside Quay
Southbank, VIC 3006
Country [1] 301827 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Zynerba Pharmaceuticals Pty Ltd
Address
2 Riverside Quay
Southbank, VIC 3006
Country
Australia
Secondary sponsor category [1] 301571 0
None
Name [1] 301571 0
Address [1] 301571 0
Country [1] 301571 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302530 0
Children's Health Queensland HREC
Ethics committee address [1] 302530 0
Lady Cilento Children’s Hospital Precinct
Level 7, 62 Graham Street
South Brisbane QLD 4101
Ethics committee country [1] 302530 0
Australia
Date submitted for ethics approval [1] 302530 0
21/01/2019
Approval date [1] 302530 0
05/03/2019
Ethics approval number [1] 302530 0
HREC/19/QCHQ/50644

Summary
Brief summary
This is an open-label single-center study, to assess the safety, tolerability and efficacy of cannabidiol administered as ZYN002, a transdermal gel, for the treatment of child and adolescent patients with Autism Spectrum Disorder (ASD). Male and female patients with ASD will be treated for 14 weeks. Patients taking Anti Epileptic Drug medications will have an additional one or two week Taper Period after the completion of doing with ZYN002. Approximately 36 male and female patients, ages 4 to < 18 years, will receive ZYN002
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 90538 0
A/Prof Helen Heussler
Address 90538 0
Children’s Health Queensland Hospital and Health Services
Queensland Children’s Hospital
501 Stanley St.
South Brisbane, QLD 4101
Country 90538 0
Australia
Phone 90538 0
+61 7 3068 2920
Fax 90538 0
Email 90538 0
h.heussler@health.qld.gov.au
Contact person for public queries
Name 90539 0
Dr Nancy R Tich
Address 90539 0
Zynerba Pharmaceuticals Inc.,
80 West Lancaster Ave., Suite 300,
Devon, PA 19333
Country 90539 0
United States of America
Phone 90539 0
+1-973-727-4117
Fax 90539 0
Email 90539 0
tichn@zynerba.com
Contact person for scientific queries
Name 90540 0
Dr Donna Gutterman
Address 90540 0
Zynerba Pharmaceuticals Inc.,
80 West Lancaster Ave., Suite 300,
Devon, PA 19333
Country 90540 0
United States of America
Phone 90540 0
+1-919-522-8828
Fax 90540 0
Email 90540 0
guttermand@zynerba.com

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 other documents available
Summary results
No Results