Effects and Safety of Test drug ZYN002, applied as a gel onto the skin of children, adolescents and young adults with a certain hereditary disease called Fragile X Syndrome

• Register: EUCTR
• Last refreshed on: 14 October 2024
• Main ID: EUCTR2021-002542-33-IE
• Date of registration: 10/08/2021
• Prospective Registration: Yes
• Primary sponsor: Zynerba Pharmaceuticals, Inc.
• Public title: Effects and Safety of Test drug ZYN002, applied as a gel onto the skin of children, adolescents and young adults with a certain hereditary disease called 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 - RECONNECT
• Date of first enrolment: 22/02/2022
• Target sample size: 204
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-002542-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Ireland, United Kingdom, United States

Contacts

• Name: Vice President, Medical
• Affiliation: Zynerba Pharmaceuticals, Inc.

• Name: Vice President, Medical
• Affiliation: Zynerba Pharmaceuticals, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female children, adolescents and young adults aged 3 to <23 years, at the time of Screening.
2. Patient resides with caregiver who will continue to provide consistent care throughout the study.
3. 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. Laboratory results outside of the reference range must be documented as not clinically significant by both the Investigator and Sponsor.
4. Patients must have a diagnosis of FXS through molecular documentation of full mutation of the FMR1 gene documented through genetic testing at Screening.
5. Patients with an ABC-CFXS Social Avoidance score of = 5 at Screening and at Visit 2.
6. Patients with a history of seizure disorders must currently be receiving treatment with a stable regimen of no more than two AEDs for the four weeks preceding study Screening; or must be seizure-free for one year if not currently receiving AEDs.
7. Patients who are taking psychotropic medication(s) should be on a stable regimen of no more than three such medications for at least four weeks preceding study Screening and must maintain that regimen throughout the study. Psychotropic medications include (but are not limited to) antipsychotics, antidepressants, anxiolytics, attention-deficit / hyperactivity disorder (ADHD) medications, and medications for sleep.
9. 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 204
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
2. Patient has transitioned to independent living or living in a residential facility such as a university setting or congregate care.
3. History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to any compound or chemical class related to ZYN002 or its excipients.
4. Exposure to any investigational drug or device =30 days prior to Screening or at any time during the study.
5. Patient has 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 Screening safety laboratories.
6. Use of cannabis or any THC or CBD-containing product within 3 months of Screening Visit or during the study (aside from ZYN002).
8. Patient is using the following AEDs: clobazam, phenobarbital, ethosuximide, felbamate, or vigabatrin.
9. Patient is using any strong inhibitor/inducer of CYP3A4 or sensitive substrate for 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, and St. John’s Wort.
10. Patients may not be taking any benzodiazepines (except single doses administered for the purposes of obtaining blood samples and ECG’s) at screening or throughout the study.
13. Patient has an acute or progressive neurological disease, psychosis, schizophrenia, or any psychiatric disorder or severe mental abnormalities (other than FXS) that are likely to require changes in drug therapy or interfere with the objectives of the study or the ability to adhere to protocol requirements.
17. 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.




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Fragile X syndrome (FXS) is a rare genetic disorder caused by the deficiency or absence of Fragile X Messenger Ribonucleoprotein 1 (FMRP), an RNA-binding protein and the gene product of the FMR1 gene. FXS is most commonly caused by silencing of the FMR1 gene due to a trinucleotide repeat expansion. In FXS patients, the relative absence of functional FMRP is associated with critical impairments in neurodevelopment and learning, as well as disruption to other neuronal and non-neuronal functions.
MedDRA version: 20.1 Level: PT Classification code 10017324 Term: Fragile X syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Product Code: ZYN002
Pharmaceutical Form: Transdermal gel
INN or Proposed INN: n/a
CAS Number: 13956-29-1
Current Sponsor code: ZYN002
Other descriptive name: CANNABIDIOL
Concentration unit: % (W/W) percent weight/weight
Concentration type: equal
Concentration number: 4.2-
Pharmaceutical form of the placebo: Transdermal gel
Route of administration of the placebo: Transdermal use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: From screening up to Week 18

Primary end point(s): Primary Endpoint:
Change from Baseline to Week 18 in the ABC-CFXS Social Avoidance subscale score in patients with complete methylation of the FMR1 gene.

Secondary Objective: To further evaluate the efficacy of ZYN002 in the treatment of symptoms of FXS.

Main Objective: To evaluate the efficacy of ZYN002 administered as a transdermal gel formulation in patients ages 3 to <23 years, in the treatment of behavioral symptoms of FXS

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: From screening up to Week 18

Secondary end point(s): Key Secondary endpoints:
1. Change from Baseline to Week 18 in ABC-CFXS Irritability subscale score in patients with complete methylation of the FMR1 gene.
2. Percent of patients with any improvement on the CaGI-C at Week 18 for Social Interactions among patients with complete methylation of the FMR1 gene.
3. Percent of patients rated as improved on the CGI-I scale (minimally, much, very much improved) at Week 18 among patients with complete methylation of the FMR1 gene.
4. Change from Baseline to Week 18 in the ABC-CFXS Social Avoidance subscale score among all randomized patients (complete and partial methylation of the FMR1 gene).

Other Secondary Efficacy Endpoints will be evaluated in the patients with complete methylation of the FMR1 gene and in all randomized patients.
-Percent of patients with a clinically meaningful within-subject improvement from Baseline in ABC-CFXS Social Avoidance subscale score at Week 18 among patients.
-Percent of patients with a clinically meaningful within-subject improvement from Baseline in ABC-CFXS Irritability subscale score at Week 18 among patients.
-Change from Baseline in ABC-CFXS Social Avoidance and Irritability subscale scores at Weeks 10 and 14 in patients.
-Change from Baseline in ABC-CFXS Socially Unresponsive/Lethargic, Stereotypy, Inappropriate Speech, and Hyperactivity subscale scores at Weeks 10, 14, and 18 in patients.
-Percent of patients with any improvement on the CaGI-C at Week 18 for Social Avoidance and Isolation, Irritable and Disruptive Behaviors, and Overall Behavior among patients.
-Percent of patients with any improvement on the CaGI-C at Week 18 for Social Interactions among all randomized patients.
-Percent of patients rated as improved on the CGI-I scale (minimally, much, very much improved) at Week 18 among all randomized patients.
-Incidence of TEAEs and SAEs by relationship to treatment and severity; incidence of SAEs/AEs leading to treatment discontinuation.
-Changes in vital signs, clinical laboratory tests, and ECG.

Secondary ID(s)

ZYN2-CL-033

NCT04977986

Source(s) of Monetary Support

Zynerba Pharmaceuticals, Inc.

Ethics review

Status: Approved
Approval date: 22/02/2022
Contact: