Open Label Extension to Assess the Long-Term Safety and Tolerability of ZYN002 in Children and Adolescents With FXS

An Open-Label Extension Study to Assess the Long-Term Safety and Tolerability of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With Fragile X Syndrome

ZYN002 is a pharmaceutically manufactured Cannabidiol that is developed as a clear gel that can be applied to the skin (called transdermal delivery).

The gel will be applied to clean, dry, intact skin of the shoulders and/or upper arms.

Participants from the ZYN2-CL-016 and ZYN2-CL-033 studies who meet the inclusion criteria and none of the exclusion criteria for study ZYN2-CL-017 are eligible.

Parents/caregivers will apply the study gel twice daily for the 52-week treatment period.

Study Overview

• Status: Enrolling by invitation
• Conditions: Fragile X Syndrome
• Intervention / Treatment: Drug: ZYN002 - Cannabidiol Transdermal Gel

Detailed Description

This is an open-label extension, multiple-center study, to assess the long-term safety and tolerability of cannabidiol administered as ZYN002, a transdermal gel, for the treatment of child and adolescent patients with Fragile X Syndrome (FXS). Male and female patients with FXS will be treated for up to 72 months. Up to 450 male and female patients, ages 3 to 18 years will be enrolled.

Parents/caregivers will apply the study gel twice daily for the 52-week treatment period.

Participants from study ZYN-CL-016 who weigh less than or equal to 35 kg, will receive 1 sachet of ZYN002, applied every 12 hours (± 2 hours).

Participants from study ZYN-CL-016 who weigh more than 35 kg will receive 2 sachets of ZYN002, applied every 12 hours (± 2 hours).

Participants from study ZYN-CL-033 who weigh less than or equal to 30 kg, will receive 1 sachet of ZYN002, applied every 12 hours (± 2 hours).

Participants from study ZYN-CL-033 who weigh more than 30 kg will receive 2 sachets of ZYN002, applied every 12 hours (± 2 hours).

Participants from study ZYN-CL-033 who weigh more than 50 kg will receive 3 sachets of ZYN002, applied every 12 hours (± 2 hours).

At the Investigator's discretion, the dose may be increased or decreased at any time after the first month of treatment (for example due to weight changes during the course of the study).

Participants who are taking anti-epileptic drugs may have an additional one or two weeks of treatment after the 52 week treatment period to taper off study treatment.

Blood samples will be collected for safety analysis of ZYN002. Additionally, the parents/caregivers will be asked to complete some questionnaires. There will be other questionnaires and scales that will be completed at the site by the study doctor and/or with the participant and their parents/caregivers.

Patients that complete Month 12 will be allowed to continue for another 12 months of treatment if they qualify. Patients will be evaluated again annually at Months 24 and 36, and 48 in order to remain in the study.

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2145
      • Westmead Children's Hospital
  • Queensland
    • Brisbane, Queensland, Australia, 4101
      • Lady Cilento Children's Hospital - South Brisbane
  • Victoria
    • Melbourne, Victoria, Australia, 3161
      • Genetics Clinics Australia
• New Zealand
  • Wellington, New Zealand, 6021
    • Wellington Hospital
• United Kingdom
  • Manchester, United Kingdom, M13 9WL
    • Manchester University NHS Foundation Trust
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom, LE15WW
      • Research Space
  • Lothian
    • Edinburgh, Lothian, United Kingdom, EH105HF
      • Children's Clinical Research Facility, Royal Hospital for Children and Young People
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Southwest Autism Research and Resource Center
  • California
    • Culver City, California, United States, 90230
      • Science 37
    • Sacramento, California, United States, 95817
      • UC Davis Health System, MIND Institute
  • Colorado
    • Denver, Colorado, United States, 80045
      • Children's Hospital of Colorado
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School of Medicine
    • Atlanta, Georgia, United States, 30329
      • Han Phan
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Kennedy Krieger Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • Masonic Institute of Developing Brain
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississipi Medical Center
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Fragile X Center of Atlantic Health System
  • New York
    • New York, New York, United States, 10029
      • The Fragile X Spectrum Disorder Clinic at Icahn School of Medicine at Mount Sinai, Division of Medical Genetics
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Central States Research
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
    • Media, Pennsylvania, United States, 19063
      • Suburban Research Associates
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenwood Genetic Center
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98198
      • University of Washington Center for Human Development and Disability

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 16 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participated in study ZYN2-CL-016 or Study ZYN2-CL-033.
• Patients and parents/caregivers agree to abide by all study restrictions and comply with all study 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.
• In the Investigator's opinion, the patients and parents/caregivers are reliable and are willing and able to comply with all protocol requirements and procedures.
• Females of childbearing potential must have a negative pregnancy test at all designated visits

Exclusion Criteria:

• Patient is receiving any investigational drugs (not ZYN002) or using any experimental devices.
• Patient has an ongoing serious adverse event (SAE) or has experienced a SAE in ZYN2-CL-016 or ZYN2-CL-033, which in the opinion of the Investigator, should exclude them from participation.
• 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 for the duration of therapy and for three months after the last dose of trial drug.
• Patients who have 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 patient safety laboratories.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ZYN002; ZYN002 - cannabidiol Transdermal Gel	Drug: ZYN002 - Cannabidiol Transdermal Gel; Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery); Other Names: Cannabidiol Transdermal Gel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the long-term safety and tolerability of ZYN002 administered as a transdermal gel formulation.	Safety assessment will include collection of any treatment emergent adverse events	Up to 72 month.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the long-term efficacy of ZYN002 in the treatment of symptoms of FXS.	Change from Baseline (last assessment prior to the first dose of ZYN002) in the ABC-CFXS subscale scores.	Change from baseline to end of treatment

Collaborators and Investigators

• Sponsor: Zynerba Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Heussler HS. Emerging Therapies and challenges for individuals with Angelman syndrome. Curr Opin Psychiatry. 2021 Mar 1;34(2):123-128. doi: 10.1097/YCO.0000000000000674. Erratum In: Curr Opin Psychiatry. 2021 Sep 1;34(5):514.

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2018
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: December 26, 2018
• First Submitted That Met QC Criteria: January 9, 2019
• First Posted (Actual): January 14, 2019

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Chromosome Disorders; Sex Chromosome Disorders; Syndrome; Fragile X Syndrome; Anticonvulsants; Cannabidiol
• Other Study ID Numbers: ZYN2-CL-017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No