Efficacy and Safety Evaluation of ZYN002 Transdermal Gel in Pediatric and Young Adult Patients with Fragile X Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study
- Trial ID
- 2024-513888-99-00
- Protocol
- ZYN2-CL-033
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of ZYN002, a transdermal gel formulation of cannabidiol (CBD), in treating the behavioral symptoms of **Fragile X Syndrome (FXS)** in patients aged 3 to less than 23 years. This objective is clinically relevant as FXS is a genetic condition that causes a range of developmental problems, including learning disabilities and cognitive impairment, and effective treatments are limited. The study aims to determine if ZYN002 can provide a therapeutic benefit in managing these symptoms, potentially improving the quality of life for affected individuals.
Secondary objectives include further evaluation of the efficacy of ZYN002 in the treatment of symptoms of FXS. This additional assessment will help to comprehensively understand the therapeutic potential and scope of ZYN002 in managing FXS symptoms beyond the primary behavioral focus.
Participants
The clinical trial involves a total of **197 participants** diagnosed with **Fragile X syndrome (FXS)**. The study population includes both male and female children, adolescents, and young adults aged 3 to less than 23 years. Participants are required to reside with a caregiver who will provide consistent care throughout the study. The individuals selected for the trial are judged to be in generally good health based on medical history, physical examination, 12-lead ECG, and clinical laboratory test results. Participants must have a confirmed diagnosis of FXS through genetic testing. Those with a history of seizure disorders must be on a stable regimen of no more than two antiepileptic drugs (AEDs) or be seizure-free for one year if not currently receiving AEDs. Additionally, participants taking psychotropic medications should maintain a stable regimen of no more than three such medications. The trial includes individuals with a body mass index (BMI) between 12 and 30 kg/m², and those with a BMI greater than 30 kg/m² but less than 40 kg/m², provided they have normal liver function and no immediate family history of fatty liver disease. The trial population was carefully selected to ensure the inclusion of a vulnerable population, with considerations for consistent care and stable medication regimens.
Plans and Procedures
The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the efficacy and safety of ZYN002, a **transdermal gel** containing **cannabidiol (CBD)**, in treating behavioral symptoms of **Fragile X syndrome (FXS)**. The trial targets male and female participants aged 3 to less than 23 years, who have been diagnosed with FXS through molecular documentation of the full mutation of the FMR1 gene. The study will be conducted over an estimated period, concluding by April 2025, with recruitment starting in June 2023. The trial will involve multiple centers and will include a placebo group for comparison.
Participants will be involved in the study for a maximum treatment period of 16 weeks. The sequence of study visits includes an initial screening visit to confirm eligibility based on inclusion criteria such as age, health status, and genetic testing results. Following the screening, participants will be randomized to receive either the active treatment or placebo. Regular follow-up visits will be scheduled to monitor the participants' health, adherence to the treatment regimen, and any adverse events. The primary endpoint is the change from baseline to Week 18 in the ABC-CFXS Social Avoidance subscale score in patients with complete methylation of the FMR1 gene. Secondary endpoints include changes in other behavioral subscale scores and the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).
The end-of-study visit will assess the overall outcomes and any long-term effects of the treatment. Participants may be withdrawn from the study early if they experience significant adverse effects, fail to adhere to the study protocol, or if the investigator deems it necessary for their safety. The study aims to provide valuable data on the potential benefits and risks of ZYN002 in managing symptoms associated with FXS, contributing to the understanding and treatment of this rare genetic disorder.
Treatment
The clinical trial involves the administration of **ZYN002 Transdermal Gel Cannabidiol (CBD)**, an experimental medication formulated as a transdermal gel. The active substance in this formulation is **cannabidiol**, a chemical compound. The gel is applied transdermally, allowing for systemic absorption through the skin. The maximum daily dose of ZYN002 is 750 mg, with a total maximum dose of 9.01 grams over the course of the treatment. The treatment period is set for a maximum of 16 weeks. The gel is not a pediatric formulation and is designated as an orphan drug under the number EU/3/22/2583. The administration of the gel is monitored to ensure compliance with the dosing schedule.
In addition to the experimental treatment, the study includes a **ZYN002 Placebo Transdermal Gel** as a comparator. The placebo is designed to mimic the appearance and application method of the active gel but does not contain any active pharmaceutical ingredients. The placebo is used to maintain the double-blind nature of the study, ensuring that neither the participants nor the investigators know which treatment is being administered. This helps in accurately assessing the efficacy and safety of the ZYN002 Transdermal Gel in treating behavioral symptoms of Fragile X Syndrome.
Efficacy
The efficacy of ZYN002 Transdermal Gel Cannabidiol (CBD) in treating behavioral symptoms of **Fragile X Syndrome (FXS)** will be assessed through a randomized, double-blind, placebo-controlled clinical trial. The primary endpoint for evaluating efficacy is the change from baseline to Week 18 in the ABC-CFXS Social Avoidance subscale score in patients with complete methylation of the FMR1 gene. Secondary endpoints include changes from baseline to Week 18 in the ABC-CFXS Irritability subscale score, the percentage of patients with any improvement on the CaGI-C for Social Interactions, and the percentage of patients rated as improved on the CGI-I scale at Week 18. Additional secondary endpoints involve changes in various ABC-CFXS subscale scores at Weeks 10, 14, and 18, as well as the incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).
Efficacy parameters will be measured using validated scales such as the ABC-CFXS, CaGI-C, and CGI-I. Data collection will occur at specified timepoints, including baseline, Weeks 10, 14, and 18. The analysis will focus on both complete and partial methylation of the FMR1 gene among all randomized patients. The trial aims to provide a comprehensive evaluation of the treatment's impact on social avoidance, irritability, and overall behavior in the target population.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male or female children, adolescents, and young adults aged 3 to <23 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 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 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 AEDs for the four weeks preceding study Screening; 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 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.
- 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.
Exclusion Criteria
- 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 ≤30 days prior to Screening or at any time during the study.
- 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.
- Use of cannabis or any THC or CBD-containing product within 3 months of Screening Visit or during the study (aside from ZYN002).
- Patient is using the following AEDs: clobazam, phenobarbital, ethosuximide, felbamate, 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, and St. John's Wort.
- 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.
- 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.
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Ireland | Not Recruiting | 20 Jun 2023 | 7 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
ZYN002 Transdermal Gel CannabidiolCBD | Test | TRANSDERMAL GEL | TRANSDERMAL USE | 750 | 16 | PRD11007565 |
ZYN002 Placebo Transdermal Gel | Placebo | N/A | — | — | — | N/A |