A study where all patients receive the test drug, in order to understand the consequences of long-term test drug use on the human body. All patients are children, adolescents and young adults who suffer from an inherited disease called Fragile X Syndrome, which affects their intellectual and behavioral development. The majority of patients in this study have previously participated in a study with the test drug, and continue taking the test drug in this study because their carers feel it had helped them.

Phase 1

Conditions: Fragile X Syndrome (FXS)
Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Registration Number: CTIS2023-508165-33-00

Lead Sponsor: Zynerba Pharmaceuticals Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 210

Inclusion Criteria

Must have completed protocol ZYN2-CL-033., Females of childbearing potential must have a negative pregnancy test at all designated visits., Male or female children and adolescents aged 3 to <23 years, at the time of entry into ZYN2-CL-033., Judged by the Investigator to be in generally good health at entry 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., 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 entry; or must be seizure-free for one year if not currently receiving AEDs., 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 entry. Psychotropic 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 entry., 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., 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., Patients and parents/caregivers must be adequately informed of the nature, risks of the study, and give written informed consent prior to enrollment in ZYN2-CL-017.

Exclusion Criteria

Patient is receiving or has received an investigational drug or device less than or equal to 30 days prior to screening, with the exception of ZYN002 or placebo in the previous Zynerba FXS trial, ZYN2-CL-033., History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to any compound or chemical class related to ZYN002 or its excipients., Patient has an advanced, severe, or unstable disease that may interfere with the study outcome evaluations., 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., 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 entry 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 completed or did not enter ZYN2-CL-033)., Patient responds yes” to Question ‘4’ or ‘5’ on the C-SSRS (Children) during Screening or at any time on study., Use of cannabis or any THC or CBD-containing product within 3 months of entry 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: clobazam, phenobarbital, ethosuximide, felbamate, carbamazepine, phenytoin, or vigabatrin., 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, 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 entry or throughout the study., Patient has an ongoing serious adverse event (SAE) or has experienced an SAE in study ZYN2-C

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the long-term safety and tolerability of ZYN002 administered as a transdermal gel formulation, for up to 48 months, in the treatment of symptoms of Fragile X Syndrome (FXS).;Secondary Objective: To evaluate the long-term efficacy of ZYN002 in the treatment of symptoms of FXS.;Primary end point(s): Safety assessments will include collection of AEs including seizure assessment if applicable, physical and neurological examinations, 12-lead ECG, safety laboratory assessments (hematology, chemistry, reproductive hormone, prolactin tests, and urinalysis), vital signs, C-SSRS, and findings from the skin irritation checks following treatment.

Secondary Outcome Measures