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/NCT05149898




Registration number
NCT05149898
Ethics application status
Date submitted
5/10/2021
Date registered
8/12/2021
Date last updated
3/11/2023

Titles & IDs
Public title
Open-Label Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With 22q11.2 Deletion Syndrome
Scientific title
Open-Label, Tolerability and Efficacy Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With 22q11.2 Deletion Syndrome
Secondary ID [1] 0 0
ZYN2-CL-031
Universal Trial Number (UTN)
Trial acronym
INSPIRE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
22Q Deletion Syndrome 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
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

Experimental: Open-label - Open-label


Treatment: Drugs: ZYN002
CBD Transdermal Gel pharmaceutically manufactured. Cannabidiol (CBD) formulated as a clear gel (transdermal delivery).
Dose received is based on weight.
Patients who weigh = 35 kg will receive 125 mg CBD Q12H (every 12 hours); for a total daily dose of 250 mg CBD.
Patients who weigh > 35 kg will receive 250 mg CBD Q12H (±2 hours); for a total daily dose of 500 mg CBD.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of treatment-emergent adverse events (safety and tolerability)
Timepoint [1] 0 0
Adverse Event time frame is from admission to a study completion, an average of 9 months
Secondary outcome [1] 0 0
Aberrant Behavior Checklist (ABC-C) Pre-specified Subscale 1
Timepoint [1] 0 0
Screening, Visit 2, Visit 3, Visit 4, Visit 5, Visit 6, and Visit 7 EOS/ET, over a 38 week period
Secondary outcome [2] 0 0
Clinical Global Impression-Severity and Improvement (CGI-S and CGI-I)
Timepoint [2] 0 0
CGI-S is collected at Screening, Visit 2, Visit 3, Visit 4, Visit 5, Visit 6, and Visit 7 EOS/ET, over a 38 week period and CGI-I will be assessed at Visit 3 and Visit 4/EOS/ET, over 14 week period
Secondary outcome [3] 0 0
Anxiety, Depression and Mood Scale (ADAMS)
Timepoint [3] 0 0
Screening, Visit 2, Visit 3, Visit 4, Visit 5, Visit 6, and Visit 7 EOS/ET, over a 38 week period
Secondary outcome [4] 0 0
Qualitative Caregiver Reported Behavioral Problems Survey
Timepoint [4] 0 0
Visit 3, Visit 4, Visit 5, Visit 6, and Visit 7 EOS/ET, over a 38 week period
Secondary outcome [5] 0 0
Pediatric Anxiety Rating Scale-Revised (PARS-R)
Timepoint [5] 0 0
Screening, Weeks 14, 22, 30, and Week 38

Eligibility
Key inclusion criteria
1. Male or female children and adolescents aged 4 to less than 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, and clinical laboratory test
results.

3. Patients must have a diagnosis of 22q Deletion Syndrome (22qDS) confirmed by genetic
testing.

4. Patients have a Clinical Global Impression-Severity (CGI-S) score of 4 or higher at
Screening and Visit 2.

5. Patients must have a Pediatric Anxiety Rating Scale-Revised (PARS-R) severity score of
10 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 for three months prior to Screening.

8. Patient has demonstrated stable calcium levels for one year prior to Screening.

9. Patients have a body mass index between 12-35 kg / m2 (inclusive).

10. Females of childbearing potential must have a negative pregnancy test at the Screening
Visit and a negative pregnancy test at all designated study visits.

11. Patients and parents/caregivers agree to abide by all study restrictions and comply
with all study procedures.

12. 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.

13. Parents/caregiver(s) must provide written consent to assist in study drug
administration.

14. 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
17 Years
Sex
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 for the duration of therapy and
for three months after the last dose of study medication.

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 = 30 days prior to Screening or at any
time during the study.

4. Patient has ALT, AST, or total bilirubin levels = 2 times the ULN)or has alkaline
phosphatase levels = 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.

7. Patient is using the following AEDs: clobazam, phenobarbital, ethosuximide, felbamate,
carbamazepine, phenytoin 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, St. John's Wort, and grapefruit juice/products.

9. Patient with diagnosis of known genetic disorder, other than 22qDS.

10. Patient has diagnosis of DiGeorge or Velocardiofacial syndrome without the presence of
22qDS.

11. Patient has a primary psychiatric diagnosis other than 22qDS or anxiety, including
bipolar disorder, psychosis, schizophrenia, PTSD or major depressive disorder.

12. Patient is on stable treatment of >6 months of not more than two psychoactive
medications at screening or throughout the study (with the exception of one
psychoactive medication prescribed for sleep).

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

14. Patient is expected to initiate or change pharmacologic or non-pharmacologic
interventions during the course of the study.

15. 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.

16. Patient has a positive result for the presence of HBsAg, HCV, or HIV antibodies.

17. Patients at risk of needing cardiovascular surgical repair within the upcoming 12
months.

18. Patient has unstable cardiovascular disease, such as advanced arteriosclerosis,
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), other serious or other clinically
unstable cardiac problems as indicated by history, physical examination, or ECG.

19. 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.

20. Any skin disease or condition that may affect treatment application, application site
assessments, or absorption of the study drug.

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

22. Patient responds "yes" to Question '4' or '5' on the Columbia Suicide Severity Rating
Scale Children (C-SSRS) during Screening or at any time on study.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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 1/Phase 2
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
3/03/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
21/11/2022
Sample size
Target
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Lady Cilento Children's Hospital - South Brisbane - Brisbane
Recruitment hospital [2] 0 0
Genetics Clinics Australia - Melbourne
Recruitment postcode(s) [1] 0 0
4101 - Brisbane
Recruitment postcode(s) [2] 0 0
3161 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
South Carolina

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

Ethics approval
Ethics application status

Summary
Brief summary
To evaluate the safety and tolerability of ZYN002 administered as a transdermal gel
formulation, for up to 38 weeks, in patients ages 4 to < 18 years, in the treatment of
22q.11.2 Deletion Syndrome (22qDS).
Trial website
https://clinicaltrials.gov/ct2/show/NCT05149898
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Carol O'Neill
Address 0 0
VP, Development
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/NCT05149898