- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04977986
Clinical Study of Cannabidiol in Children, Adolescents, and Young Adults With Fragile X Syndrome (RECONNECT)
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
Study Overview
Status
Conditions
Intervention / Treatment
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. 204 male and female patients, ages 3 to < 23 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.
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Nancy Tich, PhD
- Phone Number: 973-727-4117
- Email: tichn@harmonybiosciences.com
Study Contact Backup
- Name: Kristen Kaplan
- Email: kkaplan@harmonybiosciences.com
Study Locations
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New South Wales
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Sydney, New South Wales, Australia, 2145
- Recruiting
- Westmead Children's Hospital
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Contact:
- Desmond Thai
- Email: desmond.thai@health.nsw.gov.au
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Principal Investigator:
- Natalie Silove, MD
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Queensland
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Brisbane, Queensland, Australia, 4101
- Recruiting
- Lady Cilento Children's Hospital - South Brisbane
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Contact:
- Emily Milburn
- Email: emily.milburn@health.qld.gov.au
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Principal Investigator:
- Honey Heussler, MD
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South Australia
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Bedford Park, South Australia, Australia, 5042
- Recruiting
- Flinders Medical Centre
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Contact:
- Dylan Mordaunt, MD
- Email: dylan.mordaunt@sa.gov.au
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Principal Investigator:
- Dylan Mordaunt, MD
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Victoria
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Melbourne, Victoria, Australia, 3161
- Recruiting
- Genetics Clinics Australia
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Contact:
- Email: travel@travelclinic.com.au
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Principal Investigator:
- Jonathan Cohen, MD
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Dublin, Ireland
- Recruiting
- Wellcome HRB Clinical Research Facility
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Contact:
- Aoife Mahony, MB Bch BAO
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Principal Investigator:
- Aoife Mahony, MB Bch BAO
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Edinburgh, United Kingdom
- Recruiting
- University of Edinburgh
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Contact:
- Andrew Stanfield, MD
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Principal Investigator:
- Andrew Stanfield, MD
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Leicester, United Kingdom
- Recruiting
- Leicester Clinical Research
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Contact:
- Julian Barwell, MD
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Principal Investigator:
- Julian Barwell, MD
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London, United Kingdom
- Recruiting
- King's College
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Contact:
- Andre Strydom
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Principal Investigator:
- Andre Strydom, MD
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Manchester, United Kingdom
- Recruiting
- Manchester University NHS Foundation Trust
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Contact:
- Myfanwy "Miffy" Rawson
- Phone Number: 44 0161 701 2788
- Email: genetics.research@mft.nhs.uk
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Principal Investigator:
- Catherine Breen, MD
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California
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Culver City, California, United States, 90230
- Recruiting
- Science 37
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Principal Investigator:
- David Kudrow, MD
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Contact:
- David Kudrow, MD
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Orange, California, United States, 92868
- Recruiting
- Thompson Autism Center CHOC
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Principal Investigator:
- Sailaja Golla, MD
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Contact:
- Sailaja Golla, MD
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Sacramento, California, United States, 95817
- Recruiting
- UC Davis Health System, MIND Institute
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Contact:
- Salma Badran
- Phone Number: 916-703-0471
- Email: bsalma@ucdavis.edu
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Principal Investigator:
- Randi Hagerman, MD
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District of Columbia
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Washington, District of Columbia, United States, 20010
- Recruiting
- Children's National Medical Center
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Contact:
- Marissa Horrigan
- Email: mhorrigan@childrensnational.org
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Principal Investigator:
- Sinan Turnacioglu, MD
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Florida
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Miami, Florida, United States, 33136
- Recruiting
- University of Miami
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Contact:
- Cynthia Fundora
- Email: cxf157@miami.edu
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Principal Investigator:
- Barbara Coffey, MD
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Georgia
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Atlanta, Georgia, United States, 30318
- Recruiting
- Rare Disease Research
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Principal Investigator:
- Han Phan, MD
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Contact:
- Han Phan, MD
- Email: info@rarediseaseresearch.com
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Illinois
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Chicago, Illinois, United States, 60612
- Recruiting
- Rush University Medical Center
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Principal Investigator:
- Elizabeth Berry-Kravis, MD
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Contact:
- Anniek M Van Aarem
- Email: Anniek_m_Vanaarem@rush.edu
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Maryland
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Baltimore, Maryland, United States, 21205
- Recruiting
- Kennedy Krieger Institute
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Contact:
- Catherine Eliades
- Email: eliades@kennedykrieger.org
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Principal Investigator:
- Dejan Budimirovic, MD
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Recruiting
- Boston Children's Hospital
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Contact:
- Katherine Pawlowski
- Email: katherine.pawlowski@childrens.harvard.edu
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Principal Investigator:
- Lisa Prock, MD
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Minnesota
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Minneapolis, Minnesota, United States, 55454
- Recruiting
- University of Minnesota Fragile X Clinic (Voyager Clinic)
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Contact:
- Desirae Rambeck
- Email: drambeck@umphysicians.umn.edu
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Principal Investigator:
- Amy Esler, PhD
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Mississippi
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Jackson, Mississippi, United States, 39216
- Recruiting
- University of Mississippi
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Contact:
- Angelina Sharp
- Email: asharp@umc.edu
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Principal Investigator:
- John Ingram, MD
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New York
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New York, New York, United States, 10029
- Recruiting
- The Fragile X Spectrum Disorder Clinic at Icahn School of Medicine at Mount Sinai, Division of Medical Genetics
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Contact:
- Email: nicole.gonzalez@mssm.edu
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Principal Investigator:
- Reymundo Lozano, MD
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North Carolina
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Chapel Hill, North Carolina, United States, 27510
- Recruiting
- University of North Carolina
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Contact:
- Hannah Riehl
- Email: Hannah.Riehl@cidd.unc.edu
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Principal Investigator:
- Jamie Capal, MD
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Ohio
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Cincinnati, Ohio, United States, 45229
- Recruiting
- Cincinnati Children's Hospital Medical Center
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Contact:
- Danielle Chin
- Email: Danielle.Chin@cchmc.org
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Principal Investigator:
- Craig Erickson, MD
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Oklahoma
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Tulsa, Oklahoma, United States, 74136
- Recruiting
- Central States Research
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Contact:
- Christy Lisenbee
- Phone Number: 918-645-5400
- Email: christyl@centralstatesresearch.com
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Principal Investigator:
- Sarah Land, MD
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Pennsylvania
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Hershey, Pennsylvania, United States, 17033
- Recruiting
- Penn State Hershey Medical Center
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Principal Investigator:
- Patricia Gordon, MD
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South Carolina
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Greenville, South Carolina, United States, 29605
- Recruiting
- Greenwood Genetic Center
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Contact:
- Sarah English
- Email: senglish@ggc.org
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Principal Investigator:
- Carrie Buchanan, MD
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Utah
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Salt Lake City, Utah, United States, 84113
- Recruiting
- Primary Children's Hospital
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Contact:
- Susan Sorenson
- Email: Susan.Sorenson@imail.org
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Principal Investigator:
- Victoria Wilkins, MD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Male or female children and adolescents aged 3 to < 23 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).
- 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.
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) 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.
- Any clinically significant condition or abnormal findings at the Screening Visit that would, in the opinion of the Investigator, preclude study participation or interfere with the evaluation of the study medication.
- 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.
- History of treatment for, or evidence of, drug abuse within the past year.
- Previous participation in a ZYN002 study (with the exception of patients who were screen failures in Study ZYN2-CL-016 and did not enter Study ZYN2-CL-017).
- Patient responds "yes" to Question 4 or 5 on the C-SSRS (Children) during Screening or at any time on study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: ZYN002 - transdermal gel
Pharmaceutically manufactured.
Cannabidiol is formulated as a clear gel for transdermal delivery.
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Pharmaceutically manufactured cannabidiol formulated as a clear gel that can be applied to the skin (transdermal delivery)
Other Names:
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Placebo Comparator: Placebo transdermal gel
Placebo is formulated as a clear gel for transdermal delivery.
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Placebo formulated as a clear gel that can be applied to the skin (transdermal delivery) Other Names: Placebo Comparator Matching Placebo
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Aberrant Behavior Checklist-Community Fragile X Factor Structure (ABC-C FXS) Pre-specified Subscale 1 score in patients with complete methylation (100%) of the FMR1 gene.
Time Frame: Change from Baseline to Week 18
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The ABC-C FXS is a standard parent/caregiver reported behavioral outcome measure for use in developmental disability clinical trials
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Change from Baseline to Week 18
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Aberrant Behavior Checklist-Community, Fragile X Factor Structure (ABC-C FXS) Pre-specified Subscale 2 in patients with complete methylation (100%) 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
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Change from Baseline to Week 18
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Change on the Caregiver Global Impression of Change (CaGI-C) for Pre-specified parameter among patients with complete methylation (100%) of the FMR1 gene.
Time Frame: Change from Baseline to Week 18
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The CaGI-C global impression of change is a 7-point Likert scale designed to measure behavioral symptomatic change at a specific time compared to baseline.
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Change from Baseline to Week 18
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Clinical Global Impression- Improvement (CGI-I) scale among patients with complete methylation (100%) of the FMR1 gene.
Time Frame: Change from Baseline to Week 18
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The CGI-I global improvement item is a 7-point Likert scale to rate the behavioral change in a child at a specified time compared to baseline.
|
Change from Baseline to Week 18
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Change in ABC-C FXS pre-specified Subscale 1 among all randomized patients (complete and partial 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
|
Change from Baseline to Week 18
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Number of patients with adverse events
Time Frame: Day 1, Week 2, Week 4, Week 6, Week 10, Week 14, Week 18 and through 4-week post-dose telephone follow-up
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Collection of adverse events
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Day 1, Week 2, Week 4, Week 6, Week 10, Week 14, Week 18 and through 4-week post-dose telephone follow-up
|
Number of participants with abnormal physical and neurological exams
Time Frame: Screening, Day 1 and Week 18
|
Physical and neurological exams
|
Screening, Day 1 and Week 18
|
Number of participants with abnormal clinical laboratory results
Time Frame: Screening, Week 10 and Week 18
|
Laboratory tests and urinalysis
|
Screening, Week 10 and Week 18
|
Number of participants with abnormal vital sign results
Time Frame: Screening, Day 1, Week 2 and Week 18
|
Vital sign measurements (blood pressure, heart rate, respiratory rate and temperature)
|
Screening, Day 1, Week 2 and Week 18
|
Number of participants with abnormal ECG
Time Frame: Screening and Week 18
|
12-lead ECG
|
Screening and Week 18
|
Withdrawal characteristics of ZYN002 using the Penn Physician Withdrawal Checklist
Time Frame: Week 18 and 4-week post last dose
|
Penn Physician Withdrawal Checklist
|
Week 18 and 4-week post last dose
|
Skin tolerability as assessed using daily skin diary
Time Frame: Daily from Day 1 through Week 18
|
Daily skin irritation diary
|
Daily from Day 1 through Week 18
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
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-033
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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