Clinical Study Of caNNabidiol in childrEn and adolesCenTs With Fragile X (CONNECT-FX)

NCT03614663 | Completed Phase 2 Results FDA Drug

• 1 other identifier: ZYN2-CL-016
• Study Type: interventional
• Target: 212
• Locations: 3 countries
• Sites: 21

Brief Summary

This trial will evaluate the efficacy and safety of ZYN002, a clear cannabidiol gel that can be applied to the skin (called transdermal application) twice a day for the treatment of behavioral symptoms of Fragile X Syndrome (FXS). Eligible participants will then participate in up to a 14 week treatment period, where all participants will receive placebo or active study drug. Patients ages 3 to \< 18 years, will be eligible to participate.

Conditions

Fragile X Syndrome

Outcome Measures

Primary Outcomes (2)

• Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Social Avoidance Subscale - Full Analysis Set

  The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is from 0 to 12, and a higher value indicates a worse outcome.

  Change from Baseline to end of treatment (Week 12)

• Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Social Avoidance Subscale - Ad Hoc Analysis

  The Aberrant Behavior Checklist-Community is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials. The range for score for the subscale is from 0 and 12, and the higher score means a worse outcome.

  Change from baseline to end of treatment (Week 12)

Secondary Outcomes (6)

• Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Irritability Subscale - Full Analysis Set

  Change from baseline to end of treatment (Week 12)

• Aberrant Behavior Checklist-Community, Fragile X Factor Structure (ABC-C FXS) Socially Unresponsive/Lethargic Subscale - Full Analysis Set

  Change from baseline to end of treatment (Week 12)

• Number of Participants With Any Improvement - Clinical Global Impressions- Improvement (CGI-I) - Full Analysis Set

  Change in CGI-I at end of treatment (Week 12)

• Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Irritability Subscale - Ad Hoc Analysis

  Change from baseline in ABC-C to end of treatment (Week 12)

• Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Socially Unresponsive/Lethargic Subscale - Ad Hoc Analysis

  Change from baseline in ABC-C to end of treatment (Week 12)

Study Arms (2)

ZYN002 - Cannabidiol transdermal gel

EXPERIMENTAL

ZYN002 supplied as a transdermal gel. Patients weighing less than or equal to 35 kg will be randomized to receive either 125 mg cannabidiol Q12H or placebo. Patients weighing greater than 35 kg will be randomized to receive 250 mg cannabidiol Q12H or placebo.

Drug: ZYN002 - Cannabidiol Transdermal Gel

Placebo transdermal gel

PLACEBO COMPARATOR

Matching ZYN002 placebo supplied as a transdermal gel.

Other: Placebo Transdermal Gel

Interventions

ZYN002 - Cannabidiol Transdermal Gel DRUG

Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery)

ZYN002 - Cannabidiol transdermal gel

Placebo Transdermal Gel OTHER

Placebo formulated as a clear gel (transdermal delivery)

Also known as: Placebo Comparator, Matching Placebo

Placebo transdermal gel

Eligibility Criteria

• Age: 3 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female children and adolescents aged 3 to less than 18 years, at the time of Screening.
• Diagnosis of FXS through molecular documentation of FMR1 full mutation.
• Judged to be in good health based on physical exam, 12-lead ECG and clinical laboratory test results.
• Patients must be assessed by the Investigator as being moderately to severely impacted due to FXS.
• Patients taking psychotropic medication(s) should be on a stable regimen of not more than two such medications for at least fours weeks preceding Screening and must maintain that regimen throughout the study.
• 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 and parents/caregivers must be adequately informed of the nature and risks of the study and given written informed consent prior to Screening.
• In the Investigator's opinion, patients and parents/caregivers 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.
• 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 a strong inhibitor/inducer of CYP3A4 or sensitive substrate of CYP3A4.
• Use of minocycline for 30 days prior to screening or throughout the study.
• Use of any benzodiazepine at screening or throughout the study.
• Use of THC or CBD-containing product within three months of Screening Visit or during the study.
• Change in pharmacologic or non-pharmacologic intervention during the course of the study.
• 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.
• Patient is using the following ASMs: clobazam, phenobarbital, ethosuximide, felbamate or vigabatrin.
• Patients 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 suspected or confirmed 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 (e.g. heart failure, hypokalemia, family history of Long QT Syndrome) or other serious cardiac problems.
• History of treatment for, or evidence of drug abuse within the past year.
• Patient responds "yes" to Question 4 or 5 on the C-SSRS (Children) during Screening or at any time on study.

Sponsors & Collaborators

• Zynerba Pharmaceuticals, Inc.: lead

Study Sites (21)

Southwest Autism Research and Resource Center

Phoenix, Arizona, 85006, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

UC Davis Health System, MIND Institute

Sacramento, California, 95817, United States

Location

Children's Hospital of Colorado

Denver, Colorado, 80045, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, 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

Fragile X Center of Atlantic Health System

Morristown, New Jersey, 07960, 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

University of North Carolina

Chapel Hill, North Carolina, 27510, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Central States Research

Tulsa, Oklahoma, 74136, United States

Location

Suburban Research Associates

Media, Pennsylvania, 19063, United States

Location

Greenwood Genetic Center

Greenville, South Carolina, 29605, United States

Location

University of Washington Center for Human Development and Disability

Seattle, Washington, 98198, 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

Wellington Hospital

Wellington, 6021, New Zealand

Location

Related Publications (2)

• Berry-Kravis E, Hagerman R, Budimirovic D, Erickson C, Heussler H, Tartaglia N, Cohen J, Tassone F, Dobbins T, Merikle E, Sebree T, Tich N, Palumbo JM, O'Quinn S. A randomized, controlled trial of ZYN002 cannabidiol transdermal gel in children and adolescents with fragile X syndrome (CONNECT-FX). J Neurodev Disord. 2022 Nov 25;14(1):56. doi: 10.1186/s11689-022-09466-6.

  PMID: 36434514 DERIVED

• 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.

  PMID: 33395098 DERIVED

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

Results Point of Contact

• Title: Stephen O'Quinn, PharmD
• Organization: Zynerba Pharmaceuticals

oquinns@Zynerba.com

919-271-1339

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2018
• First Posted: August 3, 2018
• Study Start: June 12, 2018
• Primary Completion: June 14, 2020
• Study Completion: June 14, 2020
• Last Updated: July 6, 2022
• Results First Posted: June 16, 2022

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (1); AU (3); US (17)