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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03614663
Recruitment Status : Recruiting
First Posted : August 3, 2018
Last Update Posted : May 22, 2019
Information provided by (Responsible Party):
Zynerba Pharmaceuticals, Inc.

Brief Summary:
This study will evaluate the efficacy and safety of ZYN002, a clear cannabidiol (CBD) 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.

Condition or disease Intervention/treatment Phase
Fragile X Syndrome Drug: ZYN002 - CBD Transdermal Gel Other: Placebo Transdermal Gel Phase 2 Phase 3

Detailed Description:

This is a randomized, double-blind, placebo-controlled, multiple-center study, to assess the efficacy and safety of ZYN002, a pharmaceutically manufactured CBD, formulated as a transdermal gel, for the treatment of children and adolescent with FXS. Approximately 204 male and female patients, ages 3 to < 18 years, will undergo a screening process. Eligible participants will be randomized 1:1 to either trial drug or placebo and will undergo a 14-week treatment period. Randomization will be stratified by gender, weight category and geographic region. All participants may receive placebo during the trial. Participants who are taking anti-epileptic drugs may undergo an additional 1-2 weeks of blinded treatment to taper off study drug treatment. The assignment will be done by a computer generated system and neither the study doctor or the 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 35 kg, they will receive 2 sachets of the gel twice a day (1 sachet approximately every 12 hours) and if they weigh more than 35 kg, they will receive 4 sachets of gel per day (2 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 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.

After the final dose, patients will be followed weekly for 4 weeks by telephone, prior to discharge from the study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 204 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled Multiple-Center, Efficacy and Safety Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With Fragile X Syndrome
Actual Study Start Date : June 12, 2018
Estimated Primary Completion Date : July 23, 2019
Estimated Study Completion Date : October 29, 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: ZYN002 - CBD transdermal gel

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

Patients weighing greater than 35 kg will be randomized to receive 250 mg CBD Q12H or placebo.

Drug: ZYN002 - CBD Transdermal Gel
Pharmaceutically manufactured. Cannabidiol (CBD) formulated as a clear gel (transdermal delivery)

Placebo Comparator: Placebo transdermal gel
Matching ZYN002 placebo supplied as a transdermal gel.
Other: Placebo Transdermal Gel
Placebo formulated as a clear gel (transdermal delivery)
Other Names:
  • Placebo Comparator
  • Matching Placebo

Primary Outcome Measures :
  1. Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Pre-specified Subscale 1 [ Time Frame: Change from Baseline to end of treatment (Week 14) ]
    The ABC-C is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials.

Secondary Outcome Measures :
  1. Aberrant Behavior Checklist-Community, Fragile X Factor Structure (ABC-C FXS) Pre-specified Subscale 2 [ Time Frame: Change from Baseline to end of treatment (Week 14) ]
    The ABC-C is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials.

  2. Aberrant Behavior Checklist-Community, Fragile X Factor Structure (ABC-C FXS) Pre-specified Subscale 3 [ Time Frame: Change from baseline to end of treatment (Week 14) ]
    The ABC-C is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials.

  3. Clinical Global Impressions- Improvement (CGI-I) [ Time Frame: Change from baseline to end of treatment (Week 14) ]
    The CGI-I global improvement item is a 7-point Likert scale designed to measure behavioral symptomatic change at a specific time compared to baseline. CGI-I is a standard global measure of potential change with treatment in placebo-controlled pharmacotherapy trials in developmental disabilities.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   3 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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 AEDs: 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03614663

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Contact: Nancy R Tich, PhD 973-727-4117
Contact: Donna Gutterman, PharmD 919-522-8828

  Hide Study Locations
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United States, Arizona
Southwest Autism Research and Resource Center Recruiting
Phoenix, Arizona, United States, 85006
Contact: Raun Melmed, MD   
Phoenix Children's Hospital Recruiting
Phoenix, Arizona, United States, 85016
Contact: Richard Frye, MD   
United States, California
UC Davis Health System, MIND Institute Recruiting
Sacramento, California, United States, 95817
Contact: Randi Hagerman, MD   
United States, Colorado
Children's Hospital of Colorado Recruiting
Denver, Colorado, United States, 80045
Contact: Nicole Tartaglia, MD   
United States, Georgia
Emory University School of Medicine Recruiting
Atlanta, Georgia, United States, 30322
Contact: Amy Talboy, MD   
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Elizabeth Berry-Kravis, MD   
United States, Maryland
Kennedy Krieger Institute Recruiting
Baltimore, Maryland, United States, 21205
Contact: Dejan Budimirovic, MD   
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Lisa Prock, MD   
United States, New Jersey
Fragile X Center of Atlantic Health System Recruiting
Morristown, New Jersey, United States, 07960
Contact: Darius Adams, MD   
United States, New York
The Fragile X Spectrum Disorder Clinic at Icahn School of Medicine at Mount Sinai, Division of Medical Genetics Recruiting
New York, New York, United States, 10029
Contact: Reymundo Lozano, MD         
Contact: Katherine Graham-Oregan    212-659-8645   
United States, North Carolina
University of North Carolina Recruiting
Chapel Hill, North Carolina, United States, 27510
Contact: Laura Politte, MD   
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Craig Erickson, MD   
University Hospitals Cleveland Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Nora McNamara, MD   
United States, Oklahoma
Central States Research Recruiting
Tulsa, Oklahoma, United States, 74136
Contact: Whitney Deneen    918-645-5400   
Principal Investigator: Sarah Land, MD         
United States, Pennsylvania
Suburban Research Associates Recruiting
Media, Pennsylvania, United States, 19063
Contact: Shivkumar Hatti, MD   
United States, South Carolina
Greenwood Genetic Center Recruiting
Greenville, South Carolina, United States, 29605
Contact: Carrie Buchanan, MD   
United States, Washington
University of Washington Center for Human Development and Disability Recruiting
Seattle, Washington, United States, 98198
Contact: Raphael Bernier, PhD   
Australia, New South Wales
Westmead Children's Hospital Recruiting
Sydney, New South Wales, Australia, 2145
Contact: Natalie Silove, MD   
Australia, Queensland
Lady Cilento Children's Hospital - South Brisbane Recruiting
Brisbane, Queensland, Australia, 4101
Contact: Honey Heussler, MD   
Australia, Victoria
Genetics Clinics Australia Recruiting
Melbourne, Victoria, Australia, 3161
Contact: Jonathan Cohen, MD   
New Zealand
Wellington Hospital Recruiting
Wellington, New Zealand, 6021
Contact: Andrew Marshall, MD   
Sponsors and Collaborators
Zynerba Pharmaceuticals, Inc.

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Responsible Party: Zynerba Pharmaceuticals, Inc. Identifier: NCT03614663     History of Changes
Other Study ID Numbers: ZYN2-CL-016
First Posted: August 3, 2018    Key Record Dates
Last Update Posted: May 22, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Fragile X Syndrome
Pathologic Processes
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Sex Chromosome Disorders
Chromosome Disorders
Congenital Abnormalities
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Heredodegenerative Disorders, Nervous System