Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03614663




Registration number
NCT03614663
Ethics application status
Date submitted
10/07/2018
Date registered
3/08/2018
Date last updated
6/07/2022

Titles & IDs
Public title
Clinical Study Of caNNabidiol in childrEn and adolesCenTs With Fragile X (CONNECT-FX)
Scientific title
A Randomized, Double-Blind, Placebo-Controlled Multiple-Center, Efficacy and Safety Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With Fragile X Syndrome
Secondary ID [1] 0 0
ZYN2-CL-016
Universal Trial Number (UTN)
Trial acronym
CONNECT-FX
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fragile X Syndrome 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Mental Health 0 0 0 0
Learning disabilities
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ZYN002 - Cannabidiol Transdermal Gel
Other interventions - Placebo Transdermal Gel

Experimental: ZYN002 - Cannabidiol transdermal gel - ZYN002 supplied as a transdermal gel. Patients weighing less than or equal to 35 kg will be randomized to receive either 125 mg cannabidiol Q12H or placebo.
Patients weighing greater than 35 kg will be randomized to receive 250 mg cannabidiol Q12H or placebo.

Placebo Comparator: Placebo transdermal gel - Matching ZYN002 placebo supplied as a transdermal gel.


Treatment: Drugs: ZYN002 - Cannabidiol Transdermal Gel
Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery)

Other interventions: Placebo Transdermal Gel
Placebo formulated as a clear gel (transdermal delivery)
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Social Avoidance Subscale - Full Analysis Set
Timepoint [1] 0 0
Change from Baseline to end of treatment (Week 12)
Primary outcome [2] 0 0
Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Social Avoidance Subscale - Ad Hoc Analysis
Timepoint [2] 0 0
Change from baseline to end of treatment (Week 12)
Secondary outcome [1] 0 0
Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Irritability Subscale - Full Analysis Set
Timepoint [1] 0 0
Change from baseline to end of treatment (Week 12)
Secondary outcome [2] 0 0
Aberrant Behavior Checklist-Community, Fragile X Factor Structure (ABC-C FXS) Socially Unresponsive/Lethargic Subscale - Full Analysis Set
Timepoint [2] 0 0
Change from baseline to end of treatment (Week 12)
Secondary outcome [3] 0 0
Number of Participants With Any Improvement - Clinical Global Impressions- Improvement (CGI-I) - Full Analysis Set
Timepoint [3] 0 0
Change in CGI-I at end of treatment (Week 12)
Secondary outcome [4] 0 0
Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Irritability Subscale - Ad Hoc Analysis
Timepoint [4] 0 0
Change from baseline in ABC-C to end of treatment (Week 12)
Secondary outcome [5] 0 0
Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Socially Unresponsive/Lethargic Subscale - Ad Hoc Analysis
Timepoint [5] 0 0
Change from baseline in ABC-C to end of treatment (Week 12)
Secondary outcome [6] 0 0
Number of Participants With Any Improvement - Clinical Global Impressions- Improvement (CGI-I) - Ad Hoc Analysis
Timepoint [6] 0 0
Change in CGI-I at end of treatment (Week 12)

Eligibility
Key inclusion criteria
- Male or female children and adolescents aged 3 to less than 18 years, at the time of
Screening.

- Diagnosis of FXS through molecular documentation of FMR1 full mutation.

- Judged to be in good health based on physical exam, 12-lead ECG and clinical
laboratory test results.

- Patients must be assessed by the Investigator as being moderately to severely impacted
due to FXS.

- Patients taking psychotropic medication(s) should be on a stable regimen of not more
than two such medications for at least fours weeks preceding Screening and must
maintain that regimen throughout the study.

- 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.

- Patients and parents/caregivers must be adequately informed of the nature and risks of
the study and given written informed consent prior to Screening.

- 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
3 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Females who are pregnant, nursing or planning a pregnancy.

- Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin
levels greater than or equal to 2 times the upper limit of normal or alkaline
phosphatase levels greater than or equal to 3 times the upper limit of normal.

- Use of a strong inhibitor/inducer of CYP3A4 or sensitive substrate of CYP3A4.

- Use of minocycline for 30 days prior to screening or throughout the study.

- Use of any benzodiazepine at screening or throughout the study.

- Use of THC or CBD-containing product within three months of Screening Visit or during
the study.

- Change in pharmacologic or non-pharmacologic intervention during the course of the
study.

- 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 trial
drug.

- Patient is using the following ASMs: clobazam, phenobarbital, ethosuximide, felbamate
or vigabatrin.

- Patients has an advanced, severe or unstable disease that may interfere with the study
outcome evaluations.

- Patient has acute or progressive neurological disease, psychosis, schizophrenia or any
other psychiatric disorder or severe mental abnormalities (other than FXS) that are
likely to require changes in drug therapy or interfere with the study objectives or
ability to adhere to protocol requirements.

- Patient has suspected or confirmed 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 (e.g. heart
failure, hypokalemia, family history of Long QT Syndrome) or other serious cardiac
problems.

- History of treatment for, or evidence of drug abuse within the past year.

- 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
Randomised controlled 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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/06/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/06/2020
Sample size
Target
Accrual to date
Final
212
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Westmead Children's Hospital - Sydney
Recruitment hospital [2] 0 0
Lady Cilento Children's Hospital - South Brisbane - Brisbane
Recruitment hospital [3] 0 0
Genetics Clinics Australia - Melbourne
Recruitment postcode(s) [1] 0 0
2145 - Sydney
Recruitment postcode(s) [2] 0 0
4101 - Brisbane
Recruitment postcode(s) [3] 0 0
3161 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Oklahoma
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
South Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Washington
Country [16] 0 0
New Zealand
State/province [16] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Zynerba Pharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This trial will evaluate the efficacy and safety of ZYN002, a clear cannabidiol gel that can
be applied to the skin (called transdermal application) twice a day for the treatment of
behavioral symptoms of Fragile X Syndrome (FXS). Eligible participants will then participate
in up to a 14 week treatment period, where all participants will receive placebo or active
study drug. Patients ages 3 to < 18 years, will be eligible to participate.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03614663
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03614663