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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04977986




Registration number
NCT04977986
Ethics application status
Date submitted
20/07/2021
Date registered
27/07/2021

Titles & IDs
Public title
Clinical Study of Cannabidiol in Children, Adolescents, and Young Adults With Fragile X Syndrome
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, Multiple-Center, Efficacy and Safety Study of ZYN002 Administered as a Transdermal Gel to Children, Adolescents and Young Adults With Fragile X Syndrome - RECONNECT
Secondary ID [1] 0 0
ZYN2-CL-033
Universal Trial Number (UTN)
Trial acronym
RECONNECT
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 - transdermal gel
Treatment: Drugs - Placebo

Experimental: ZYN002 - transdermal gel - Pharmaceutically manufactured. Cannabidiol is formulated as a clear gel for transdermal delivery.

Placebo comparator: Placebo transdermal gel - Placebo is formulated as a clear gel for transdermal delivery.


Treatment: Drugs: ZYN002 - transdermal gel
Pharmaceutically manufactured cannabidiol formulated as a clear gel that can be applied to the skin (transdermal delivery)

Treatment: Drugs: Placebo
Placebo formulated as a clear gel that can be applied to the skin (transdermal delivery)

Other Names:

Placebo Comparator Matching Placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Pre-specified Subscale 1 score in patients with complete methylation of the FMR1 gene.
Timepoint [1] 0 0
Change from Baseline to Week 18
Secondary outcome [1] 0 0
Aberrant Behavior Checklist-Community, Fragile X Factor Structure (ABC-C FXS) Pre-specified Subscale 2 in patients with complete methylation of the FMR1 gene.
Timepoint [1] 0 0
Change from Baseline to Week 18
Secondary outcome [2] 0 0
Change on the Caregiver Global Impression of Change (CaGI-C) for Pre-specified parameter among patients with complete methylation of the FMR1 gene.
Timepoint [2] 0 0
Change from Baseline to Week 18
Secondary outcome [3] 0 0
Clinical Global Impression- Improvement (CGI-I) scale among patients with complete methylation of the FMR1 gene.
Timepoint [3] 0 0
Change from Baseline to Week 18
Secondary outcome [4] 0 0
Change in ABC-C FXS pre-specified Subscale 1 among all randomized patients (complete and partial methylation of the FMR1 gene).
Timepoint [4] 0 0
Change from Baseline to Week 18
Secondary outcome [5] 0 0
Number of patients with adverse events
Timepoint [5] 0 0
Day 1, Week 2, Week 4, Week 6, Week 10, Week 14, Week 18 and through 4-week post-dose telephone follow-up
Secondary outcome [6] 0 0
Number of participants with abnormal physical and neurological exams
Timepoint [6] 0 0
Screening, Day 1 and Week 18
Secondary outcome [7] 0 0
Number of participants with abnormal clinical laboratory results
Timepoint [7] 0 0
Screening, Week 10 and Week 18
Secondary outcome [8] 0 0
Number of participants with abnormal vital sign results
Timepoint [8] 0 0
Screening, Day 1, Week 2 and Week 18
Secondary outcome [9] 0 0
Number of participants with abnormal ECG
Timepoint [9] 0 0
Screening and Week 18
Secondary outcome [10] 0 0
Withdrawal characteristics of ZYN002 using the Penn Physician Withdrawal Checklist
Timepoint [10] 0 0
Week 18 and 4-week post last dose
Secondary outcome [11] 0 0
Skin tolerability as assessed using daily skin diary
Timepoint [11] 0 0
Daily from Day 1 through Week 18

Eligibility
Key inclusion criteria
* Male or female children and adolescents aged 3 to < 30 years, at the time of Screening.
* Patient resides with caregiver who will continue to provide consistent care throughout the study.
* Judged by the Investigator to be in generally good health at Screening based upon the results of medical history, physical exam, 12-lead ECG and clinical laboratory test results. -Laboratory results outside the reference range must be documented as not clinically significant by both the Investigator and Sponsor.
* Participants must have a diagnosis of FXS through molecular documentation of full mutation of the FMR1 gene documented through genetic testing at Screening.
* Patients with a history of seizure disorders must currently be receiving treatment with a stable regimen of no more than two anti-seizure medications (ASMs) for the four weeks preceding study Screening; or must be seizure-free for one year if not currently receiving ASMs.
* Patients taking psychoactive medication(s) should be on a stable regimen of not more than three such medications for at least fours weeks preceding Screening and must maintain that regimen throughout the study. Psychoactive medications include (but are not limited to) antipsychotics, antidepressants, anxiolytics, attention-deficit / hyperactivity disorder (ADHD) medications, and medications for sleep.
* 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 have a body mass index between 12-30 kg/m2 (inclusive) and patients with a body mass index >30 kg/m2 and <40 kg/m2 with normal liver function laboratory values and with no immediate family history of fatty liver disease.
* Females of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative serum or urine pregnancy test at all designated visits.
* Patients and parents/caregivers must be adequately informed of the nature and risks of the study and given written informed consent prior to Screening.
* Patients and parents/caregivers agree to abide by all study restrictions and comply with all study procedures, and in the Investigator's opinion, are reliable and willing and able to comply with all protocol requirements and procedures.
Minimum age
3 Years
Maximum age
29 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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 (defined as refraining from heterosexual intercourse from screening to three months after the last dose of study medication: abstinence only applicable for females <18 years) or the use of a highly effective method of contraception, including hormonal contraception, diaphragm, cervical cap, vaginal sponge, condom, spermicide, vasectomy, or intrauterine device. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception.
* Patient has transitioned to independent living or living in a residential facility such as a university setting or congregate care.
* History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to any compound or chemical class related to ZYN002 or its excipients.
* Exposure to any investigational drug or device less than or equal to 30 days prior to Screening or at any time during the study.
* 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 cannabis or any THC or CBD-containing product within 3 months of Screening Visit or during the study (aside from ZYN002).
* Patient has a positive drug screen, including ethanol, cocaine, THC, barbiturates, amphetamines (unless prescribed), benzodiazepines (except midazolam or comparable administered for blood draws and ECG collection), and opiates.
* Patient is using the following AEDs (medications for the treatment of seizures and/ or epilepsy): clobazam, phenobarbital, ethosuximide, felbamate, carbamazepine, phenytoin, or vigabatrin.
* Patient is using a strong inhibitor/inducer of CYP3A4 or sensitive substrate of CYP3A4 including but not limited to the following medications: midazolam (except single doses administered for the purposes of obtaining blood samples and ECG's), 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, St. John's Wort, and grapefruit Juice/products.
* Patients may not be taking any benzodiazepines (except single doses administered for the purposes of obtaining blood samples and ECGs) at screening or throughout the study.
* Patient is expected to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study.
* Patient 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 a positive result for the presence of HBsAg, HCV, or HIV antibodies.
* 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.
* 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.
* 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.
* History of treatment for, or evidence of, drug abuse within the past year.
* Previous participation in a ZYN002 study (with the exception of patients who were screen failures in Study ZYN2-CL-016 and did not enter Study ZYN2-CL-017).
* 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 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/09/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2025
Actual
Sample size
Target
250
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,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
Flinders University - Bedford Park
Recruitment hospital [4] 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
5042 - Bedford Park
Recruitment postcode(s) [4] 0 0
3161 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
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
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Mississippi
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Oklahoma
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
South Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Utah
Country [15] 0 0
Ireland
State/province [15] 0 0
Dublin
Country [16] 0 0
New Zealand
State/province [16] 0 0
Wellington
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Edinburgh
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Leicester
Country [19] 0 0
United Kingdom
State/province [19] 0 0
London
Country [20] 0 0
United Kingdom
State/province [20] 0 0
Manchester

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Nancy Tich, PhD
Address 0 0
Country 0 0
Phone 0 0
973-727-4117
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

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

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04977986