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
Overview
- Phase
- Phase 3
- Intervention
- ZYN002 - transdermal gel
- Conditions
- Fragile X Syndrome
- Sponsor
- Zynerba Pharmaceuticals, Inc.
- Enrollment
- 215
- Locations
- 27
- Primary Endpoint
- Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Pre-specified Subscale 1 score in patients with complete methylation of the FMR1 gene.
- Status
- Completed
- Last Updated
- 4 months ago
Overview
Brief Summary
This is a randomized, double-blind, placebo-controlled, multiple-center study, to assess the efficacy and safety of Cannabidiol administered as ZYN002 for the treatment of children, adolescent, and young adult patients with Fragile X Syndrome (FXS). Eligible participants will participate in up to an 18-week treatment period, where all participants will receive placebo or active study drug. Patients ages 3 to < 30 years will be eligible to participate.
Detailed Description
This is a randomized, double-blind, placebo-controlled, multiple-center study, to assess the efficacy and safety of ZYN002, a pharmaceutically manufactured cannabidiol, formulated as a clear gel that can be applied to the skin (called transdermal delivery), in children, adolescents, and young adults with FXS. 250 male and female patients, ages 3 to \< 30 years, will be randomized 1:1 to either trial drug or placebo and will undergo an 18-week treatment period. Randomization will be stratified by gender, methylation status and weight. The study will be comprised of a Screening visit and a combination of seven visits both onsite (face-to-face) and virtual. The assignment of study drug or placebo will be done by a computer-generated system and neither the study doctor, participant or their caregivers will know which treatment is being given to them. The dose of the treatment will depend on the weight of the participants. If the participants weigh less than or equal to 30 kg, they will receive 2 sachets of the gel per day (1 sachet approximately every 12 hours). If the participant weighs more than 30 kg but less than or equal to 50 kg, they will receive 4 sachets of gel per day (2 sachets approximately every 12 hours). Participants who weigh more than 50 kg will receive 6 sachets of gel per day (3 sachets approximately every 12 hours). Parents/ caregivers will be instructed on proper application of the gel. The gel will be applied to clean, dry, intact skin of the upper arms/ shoulders. Blood samples will be collected for safety analysis of ZYN002. An independent analytical laboratory will also perform CGG repeat and methylation status analyses. Additionally, the parents/caregivers and study doctor will be asked to complete some questionnaires for efficacy and safety assessment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female children and adolescents aged 3 to \< 30 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 medical history, physical exam, 12-lead ECG and clinical laboratory test results. -Laboratory results outside the reference range must be documented as not clinically significant by both the Investigator and Sponsor.
- •Participants 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 anti-seizure medications (ASMs) for the four weeks preceding study Screening; or must be seizure-free for one year if not currently receiving ASMs.
- •Patients taking psychoactive medication(s) should be on a stable regimen of not more than three such medications for at least fours weeks preceding Screening and must maintain that regimen throughout the study. Psychoactive 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 screening.
- •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.
- •Females of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative serum or urine pregnancy test at all designated visits.
- •Patients and parents/caregivers must be adequately informed of the nature and risks of the study and given written informed consent prior to Screening.
Exclusion Criteria
- •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 as outlined below for the duration of therapy and for three months after the last dose of study medication. Standard acceptable methods of contraception include abstinence (defined as refraining from heterosexual intercourse from screening to three months after the last dose of study medication: abstinence only applicable for females \<18 years) or the use of a highly effective method of contraception, including hormonal contraception, diaphragm, cervical cap, vaginal sponge, condom, spermicide, vasectomy, or intrauterine device. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception.
- •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 less than or equal to 30 days prior to Screening or at any time during the study.
- •Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or total bilirubin levels greater than or equal to 2 times the upper limit of normal or alkaline phosphatase levels greater than or equal to 3 times the upper limit of normal.
- •Use of cannabis or any THC or CBD-containing product within 3 months of Screening Visit 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 (medications for the treatment of seizures and/ or epilepsy): clobazam, phenobarbital, ethosuximide, felbamate, carbamazepine, phenytoin, or vigabatrin.
- •Patient is using a strong inhibitor/inducer of CYP3A4 or sensitive substrate of 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 screening or throughout the study.
Arms & Interventions
ZYN002 - transdermal gel
Pharmaceutically manufactured. Cannabidiol is formulated as a clear gel for transdermal delivery.
Intervention: ZYN002 - transdermal gel
Placebo transdermal gel
Placebo is formulated as a clear gel for transdermal delivery.
Intervention: Placebo
Outcomes
Primary Outcomes
Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Pre-specified Subscale 1 score in patients with complete methylation of the FMR1 gene.
Time Frame: Change from Baseline to Week 18
The ABC-C FXS is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials
Secondary Outcomes
- Number of patients with adverse events(Day 1, Week 2, Week 4, Week 6, Week 10, Week 14, Week 18 and through 4-week post-dose telephone follow-up)
- Withdrawal characteristics of ZYN002 using the Penn Physician Withdrawal Checklist(Week 18 and 4-week post last dose)
- Aberrant Behavior Checklist-Community, Fragile X Factor Structure (ABC-C FXS) Pre-specified Subscale 2 in patients with complete methylation of the FMR1 gene.(Change from Baseline to Week 18)
- Number of participants with abnormal ECG(Screening and Week 18)
- Skin tolerability as assessed using daily skin diary(Daily from Day 1 through Week 18)
- Clinical Global Impression- Improvement (CGI-I) scale among patients with complete methylation of the FMR1 gene.(Change from Baseline to Week 18)
- Number of participants with abnormal physical and neurological exams(Screening, Day 1 and Week 18)
- Number of participants with abnormal clinical laboratory results(Screening, Week 10 and Week 18)
- Number of participants with abnormal vital sign results(Screening, Day 1, Week 2 and Week 18)
- Change on the Caregiver Global Impression of Change (CaGI-C) for Pre-specified parameter among patients with complete methylation of the FMR1 gene.(Change from Baseline to Week 18)
- Change in ABC-C FXS pre-specified Subscale 1 among all randomized patients (complete and partial methylation of the FMR1 gene).(Change from Baseline to Week 18)