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.
Conditions
Interventions
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) p
Sponsors
Zynerba Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female children, adolescents and young adults aged 3 to 30 kg/m2 and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 Objective: To further evaluate the efficacy of ZYN002 in the treatment of symptoms of FXS.;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.;Timepoint(s) of evaluation of this end point: From screening up to Week 18 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
Australia, Ireland, United Kingdom, United States
Contacts
Public ContactVice President, Medical
Zynerba Pharmaceuticals, Inc.
Outcome results
None listed