Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618001868279
Ethics application status
Approved
Date submitted
13/11/2018
Date registered
16/11/2018
Date last updated
16/11/2018
Date data sharing statement initially provided
16/11/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Clinical study Of caNNabidiol in children and adolesCenTs with Fragile X Open-Label Extension (CONNECT-FX OLE)
Scientific title
An Open-Label Extension Study to Assess the Long-Term Safety and Tolerability of ZYN002 Administered as a Transdermal Gel to Children and Adolescents with Fragile X Syndrome – CONNECT-FX Open Label Extension (OLE)
Secondary ID [1] 291615 0
ZYN2-CL-017
Universal Trial Number (UTN)
Trial acronym
CONNECT-FX OLE
Linked study record
This record is an extension of ACTRN12618001063202.

Health condition
Health condition(s) or problem(s) studied:
Fragile X Syndrome 310322 0
Condition category
Condition code
Human Genetics and Inherited Disorders 309052 309052 0 0
Other human genetics and inherited disorders
Neurological 309053 309053 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
ZYN002 is a pharmaceutically manufactured Cannabidiol (CBD) that is developed as a clear gel that can be applied to the skin (called transdermal delivery).

The gel will be applied to clean, dry, intact skin of the shoulders and/or upper arms.

Only participants from the ZYN2-CL-016 study who meet the inclusion criteria and none of the exclusion criteria for study ZYN2-CL-017 are eligible.

Parents/caregivers will apply the study gel twice daily for the 52-week treatment period.
Participants who weigh less than or equal to 35 kg, will receive 1 sachet of ZYN002, applied every 12 hours (± 2 hours).
Participants who weigh more than 35 kg will receive 2 sachets of ZYN002, applied every 12 hours (± 2 hours).
At the Investigator’s discretion, the dose may be increased to a total of 4 sachets a day or decreased to a total of 2 sachets a day any time after the first month of treatment.

Participants who are taking Anti-epileptic drugs may have an additional one or two weeks of treatment after the 52 week treatment period to taper off study treatment.

Participant compliance with the intervention will be monitored by the study coordinator through drug accountability at each study visit.
Intervention code [1] 312844 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 308017 0
To evaluate the long-term safety and tolerability of ZYN002.
Safety assessments will include collection of any adverse events, physical and neurological exams (including Tanner staging), clinical laboratory safety assessments (hematology, chemistry and urinalysis), vital signs and 12-lead ECGs. Finally, 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] 308017 0
Safety and tolerability will be assessed at every study visit from Day 1 to end of treatment, including Day 1, Months 1, 3, 6, 9 and 12, any Unscheduled Visits and the taper period.
Secondary outcome [1] 353660 0
The change in the Aberrant Behavior Checklist – Community Fragile X factor (ABC-C) Pre-specified Subscale 1
Timepoint [1] 353660 0
Change from Baseline to End of Treatment. Subscale 1 to be assessed at all study visits: Months 1, 3, 6, 9 and 12/Early Termination (ET)
Secondary outcome [2] 353661 0
Change in the ABC-C Fragile X factor Pre-specifed Subscale 2
Timepoint [2] 353661 0
Change from Baseline to End of Treatment. Subscale 2 to be assessed at all study visits: Months 1, 3, 6, 9 and 12/Early Termination (ET)
Secondary outcome [3] 353662 0
Change in the ABC-C Fragile X factor Pre-specifed Subscale 3
Timepoint [3] 353662 0
Change from Baseline to End of Treatment. Subscale 3 to be assessed at all study visits: Months 1, 3, 6, 9 and 12/Early Termination (ET)
Secondary outcome [4] 353663 0
Change in Caregiver Global Impression of Change (CGI-)I
Timepoint [4] 353663 0
Change from Baseline to End of Treatment. Assessed at Months 6 and 12/ET

Eligibility
Key inclusion criteria
1. Participated in a certain number of visits in the ZYN2-CL-016 study
2. Patients and parents/caregivers agree to abide by all study restrictions and comply with all study procedures.
3. Patients and parents/caregivers must be adequately informed of the nature, risks of the study, and give written informed consent prior to enrollment in ZYN2-CL-017.
4. In the Investigator’s opinion, the patients and parents/caregivers are reliable and are willing and able to comply with all protocol requirements and procedures.
5. Females of childbearing potential must have a negative pregnancy test at all designated visits
Minimum age
3 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patient is receiving any investigational drugs (not ZYN002) or using any experimental devices.
2. Patient has an ongoing serious adverse event (SAE) or has experienced a SAE in ZYN2-CL-016, which in the opinion of the Investigator, should exclude them from participation.
3. 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 trial drug.
4. Patients who have alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels = 2 times the upper limit of normal (ULN) or has alkaline phosphatase levels = 3 times the ULN as determined from patient safety laboratories.

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
Safety/efficacy
Statistical methods / analysis
Descriptive statistics (include 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.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
8/11/2018
Date of last participant enrolment
Anticipated
30/09/2019
Actual
Date of last data collection
Anticipated
30/09/2020
Actual
Sample size
Target
300
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 12368 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment hospital [2] 12369 0
Fragile X Alliance Inc. - Caulfield North
Recruitment hospital [3] 12370 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 24631 0
4101 - South Brisbane
Recruitment postcode(s) [2] 24632 0
3161 - Caulfield North
Recruitment postcode(s) [3] 24633 0
2145 - Westmead
Recruitment outside Australia
Country [1] 21003 0
United States of America
State/province [1] 21003 0
Multiple Sites
Country [2] 21004 0
New Zealand
State/province [2] 21004 0
Wellington

Funding & Sponsors
Funding source category [1] 296106 0
Commercial sector/Industry
Name [1] 296106 0
Zynerba Pharmaceuticals Pty. Ltd.
Country [1] 296106 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Zynerba Pharmaceuticals Pty. Ltd
Address
2 Riverside Quay
Soutbank, VIC 3006
Country
Australia
Secondary sponsor category [1] 300742 0
None
Name [1] 300742 0
Address [1] 300742 0
Country [1] 300742 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297361 0
Bellberry HREC
Ethics committee address [1] 297361 0
129 Glen Osmond Road Eastwood South Australia 5063
Ethics committee country [1] 297361 0
Australia
Date submitted for ethics approval [1] 297361 0
10/10/2018
Approval date [1] 297361 0
07/11/2018
Ethics approval number [1] 297361 0
Ethics committee name [2] 301871 0
Children's Health Queensland HREC
Ethics committee address [2] 301871 0
Lady Cilento Children’s Hospital Precinct Level 7, 62 Graham Street
South Brisbane QLD 4101
Ethics committee country [2] 301871 0
Australia
Date submitted for ethics approval [2] 301871 0
26/11/2018
Approval date [2] 301871 0
Ethics approval number [2] 301871 0

Summary
Brief summary
This study is evaluating the long term and safety and tolerability of ZYN002, a clear gel that can be applied to the skin (called transdermal application) twice a day for treatment of symptoms of Fragile X Syndrome (FXS)

Who is it for?
Patients who have been diagnosed with Fragile X Syndrome and are aged between 3 and 18 years old who have participated in the ZYN2-CL-016 double-blind study and meet certain eligibility criteria.

Study details
Eligible participants will undergo up to a 52-week treatment period. Participants who are taking anti-epileptic drugs may undergo an additional 1-2 weeks of treatment to taper off study drug treatment. All participants will be assigned to ZYN002. Parents/ caregivers will be instructed on proper application of the gel. The gel will be applied to clean, dry, intact skin of the upper arms/ shoulders.

Participants whose weight changes during the course of the study may have their doses changed at the investigator’s discretion on or after the Month 1 visit, or reduced due to tolerability issues at investigator’s discretion.

Blood samples will be collected for safety analysis of ZYN002. Additionally, the parents/caregivers will be asked to complete some questionnaires. There will be other questionnaires and scales that will be completed at the site by the study doctor and/or with the participant and their parents/caregivers.

Participation in this study may help the child’s/ adolescent’s FXS symptoms; however, we cannot guarantee that he/ she will get any benefits from this study. The results of this study may benefit future patients.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73806 0
Dr Helen Heussler
Address 73806 0
Lady Cilento Children's Hospital
501 Stanley St, South Brisbane 4101
Country 73806 0
Australia
Phone 73806 0
+617 3068 2920
Fax 73806 0
Email 73806 0
h.heussler@health.qld.gov.au
Contact person for public queries
Name 73807 0
Dr Nancy R. Tich
Address 73807 0
Zynerba Pharmaceuticals Inc.,80 West Lancaster Ave., Suite 300, Devon, PA 19333
Country 73807 0
United States of America
Phone 73807 0
+1-973-727-4117
Fax 73807 0
Email 73807 0
Tichn@zynerba.com
Contact person for scientific queries
Name 73808 0
Dr Donna Gutterman
Address 73808 0
Zynerba Pharmaceuticals Inc., 80 West Lancaster Ave., Suite 300, Devon, PA 19333
Country 73808 0
United States of America
Phone 73808 0
+1-919-522-8828
Fax 73808 0
Email 73808 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