Clinical Study of Cannabidiol in Children, Adolescents, and Young Adults With Fragile X Syndrome

NCT04977986 | Completed Phase 3 FDA Drug

• 1 other identifier: ZYN2-CL-033
• Study Type: interventional
• Target: 215
• Locations: 5 countries
• Sites: 27

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.

Conditions

Fragile X Syndrome

Keywords

Human Genetics and Inherited Disorders; Other human genetics and inherited disorders

Outcome Measures

Primary Outcomes (1)

• 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.

  The ABC-C FXS is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials

  Change from Baseline to Week 18

Secondary Outcomes (11)

• 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

• 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

• Clinical Global Impression- Improvement (CGI-I) scale 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

• 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

Study Arms (2)

ZYN002 - transdermal gel

EXPERIMENTAL

Pharmaceutically manufactured. Cannabidiol is formulated as a clear gel for transdermal delivery.

Drug: ZYN002 - transdermal gel

Placebo transdermal gel

PLACEBO COMPARATOR

Placebo is formulated as a clear gel for transdermal delivery.

Drug: Placebo

Interventions

ZYN002 - transdermal gel DRUG

Pharmaceutically manufactured cannabidiol formulated as a clear gel that can be applied to the skin (transdermal delivery)

Also known as: cannabidiol formulated as a clear gel that can be applied to the skin (transdermal delivery)

ZYN002 - transdermal gel

Placebo DRUG

Placebo formulated as a clear gel that can be applied to the skin (transdermal delivery) Other Names: Placebo Comparator Matching Placebo

Also known as: Placebo Comparator, Matching Placebo

Placebo transdermal gel

Eligibility Criteria

• Age: 3 Years - 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• Patient is expected to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study.
• Patient has an advanced, severe, or unstable disease that may interfere with the study outcome evaluations.
• Patient has acute or progressive neurological disease, psychosis, schizophrenia or any other psychiatric disorder or severe mental abnormalities (other than FXS) that are likely to require changes in drug therapy or interfere with the study objectives or 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.

Sponsors & Collaborators

• Zynerba Pharmaceuticals, Inc.: lead

Study Sites (27)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Science 37

Culver City, California, 90230, United States

Location

Amnova Clinical Research, LLC

Irvine, California, 92604, United States

Location

Thompson Autism Center CHOC

Orange, California, 92868, United States

Location

UC Davis Health System, MIND Institute

Sacramento, California, 95817, United States

Location

Children's National Medical center

Washington D.C., District of Columbia, 20010, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Rare Disease Research

Atlanta, Georgia, 30318, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Minnesota Fragile X Clinic (Voyager Clinic)

Minneapolis, Minnesota, 55454, United States

Location

University of Mississippi

Jackson, Mississippi, 39216, United States

Location

The Fragile X Spectrum Disorder Clinic at Icahn School of Medicine at Mount Sinai, Division of Medical Genetics

New York, New York, 10029, United States

Location

Central States Research

Tulsa, Oklahoma, 74136, United States

Location

Penn State Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Greenwood Genetic Center

Greenville, South Carolina, 29605, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

Westmead Children's Hospital

Sydney, New South Wales, 2145, Australia

Location

Lady Cilento Children's Hospital - South Brisbane

Brisbane, Queensland, 4101, Australia

Location

Genetics Clinics Australia

Melbourne, Victoria, 3161, Australia

Location

Wellcome HRB Clinical Research Facility

Dublin, Ireland

Location

Health New Zealand - Te Whatu Ora - Wellington Hospital

Newtown, Wellington Region, 6021, New Zealand

Location

University of Edinburgh

Edinburgh, United Kingdom

Location

Leicester Clinical Research

Leicester, United Kingdom

Location

King's College

London, United Kingdom

Location

Manchester University NHS Foundation Trust

Manchester, United Kingdom

Location

MeSH Terms

Conditions

Fragile X Syndrome

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Sex Chromosome Disorders; Chromosome Disorders; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo formulated as a clear gel (transdermal delivery)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, Double-Blind, Placebo-controlled, multiple center study

Study Record Dates

• First Submitted: July 20, 2021
• First Posted: July 27, 2021
• Study Start: September 13, 2021
• Primary Completion: August 29, 2025
• Study Completion: August 29, 2025
• Last Updated: December 17, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (18); IE (1); NZ (1); GB (4); AU (3)