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Fragile X SyndromePhase 3RECONNECTNCT04977986

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

A Phase 3 study testing ZYN002 in people with Fragile X Syndrome and Fragile X Syndrome (FXS), run by Harmony Biosciences Management, Inc. at 27 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 3 to 29 years
Conditions the study is for
Fragile X Syndrome, Fragile X Syndrome (FXS)
What is being tested?
ZYN002
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
257 participants
Where
27 sitesin 5 countries
Study dates
13 Sep 2021to 29 Aug 2025
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 29 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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).
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  • 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.

Trial locations and contacts

27 sites in 5 countries.

27 sites in 5 countries

United States18 sites
  • Rare Disease Research

    Atlanta, Georgia, 30318

  • Kennedy Krieger Institute

    Baltimore, Maryland, 21205

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Science 37

    Culver City, California, 90230

  • Greenwood Genetic Center

    Greenville, South Carolina, 29605

  • Penn State Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • Amnova Clinical Research, LLC

    Irvine, California, 92604

  • University of Mississippi

    Jackson, Mississippi, 39216

  • University of Miami

    Miami, Florida, 33136

  • University of Minnesota Fragile X Clinic (Voyager Clinic)

    Minneapolis, Minnesota, 55454

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

    New York, New York, 10029

  • Thompson Autism Center CHOC

    Orange, California, 92868

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016

  • UC Davis Health System, MIND Institute

    Sacramento, California, 95817

  • Primary Children's Hospital

    Salt Lake City, Utah, 84113

  • Central States Research

    Tulsa, Oklahoma, 74136

  • Children's National Medical center

    Washington D.C., District of Columbia, 20010

Other trials in United States

United Kingdom4 sites
  • University of Edinburgh

    Edinburgh

  • Leicester Clinical Research

    Leicester

  • King's College

    London

  • Manchester University NHS Foundation Trust

    Manchester

Other trials in United Kingdom

Australia3 sites
  • Lady Cilento Children's Hospital - South Brisbane

    Brisbane, Queensland, 4101

  • Genetics Clinics Australia

    Melbourne, Victoria, 3161

  • Westmead Children's Hospital

    Sydney, New South Wales, 2145

Other trials in Australia

Ireland1 site
  • Wellcome HRB Clinical Research Facility

    Dublin

Other trials in Ireland

New Zealand1 site
  • Health New Zealand - Te Whatu Ora - Wellington Hospital

    Newtown, Wellington Region, 6021

Other trials in New Zealand

About this study

Official title: 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

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.

Read the detailed description

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.

Being tested
ZYN002, Placebo
Keywords
Human Genetics and Inherited Disorders, Other human genetics and inherited disorders
Medical subject headings
Fragile X Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZYN002Drug

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

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

  • PlaceboDrug

    Also called Placebo Comparator, Matching Placebo

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

    Other Names:

    Placebo Comparator Matching Placebo

Study groups in NCT04977986
Study groupRoleWhat they receive
ZYN002ExperimentalPharmaceutically manufactured cannabidiol, which is formulated as a clear gel for transdermal delivery.
Receives: Drug: ZYN002
PlaceboPlacebo comparatorPlacebo is formulated as a clear gel for transdermal delivery.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Change from Baseline to Week 18

Secondary outcomes (11)
  1. Aberrant Behavior Checklist-Community, Fragile X Factor Structure (ABC-C FXS) Pre-specified Subscale 2 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

    Measured: Change from Baseline to Week 18

  2. Change on the Caregiver Global Impression of Change (CaGI-C) for Pre-specified parameter among patients with complete methylation of the FMR1 gene.

    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.

    Measured: Change from Baseline to Week 18

  3. Clinical Global Impression- Improvement (CGI-I) scale among patients with complete methylation of the FMR1 gene.

    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.

    Measured: Change from Baseline to Week 18

  4. Change in ABC-C FXS pre-specified Subscale 1 among all randomized patients (complete and partial 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

    Measured: Change from Baseline to Week 18

  5. Number of patients with adverse events

    Collection of adverse events

    Measured: Day 1, Week 2, Week 4, Week 6, Week 10, Week 14, Week 18 and through 4-week post-dose telephone follow-up

  6. Number of participants with abnormal physical and neurological exams

    Physical and neurological exams

    Measured: Screening, Day 1 and Week 18

  7. Number of participants with abnormal clinical laboratory results

    Laboratory tests and urinalysis

    Measured: Screening, Week 10 and Week 18

  8. Number of participants with abnormal vital sign results

    Vital sign measurements (blood pressure, heart rate, respiratory rate and temperature)

    Measured: Screening, Day 1, Week 2 and Week 18

  9. Number of participants with abnormal ECG

    12-lead ECG

    Measured: Screening and Week 18

  10. Withdrawal characteristics of ZYN002 using the Penn Physician Withdrawal Checklist

    Penn Physician Withdrawal Checklist

    Measured: Week 18 and 4-week post last dose

  11. Skin tolerability as assessed using daily skin diary

    Daily skin irritation diary

    Measured: Daily from Day 1 through Week 18

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jul 2021
  2. Study start13 Sep 2021
  3. Primary completion29 Aug 2025
  4. Study completion29 Aug 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Randomized, double-blind, placebo-controlled, multiple center study
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
257 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04977986
Sponsor's protocol ID
ZYN2-CL-033
Acronym
RECONNECT
Status last verified
Aug 2026
First submitted
20 Jul 2021
Last updated
1 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ZYN002 in people with Fragile X Syndrome and Fragile X Syndrome (FXS), run by Harmony Biosciences Management, Inc. at 27 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in United States, United Kingdom, Australia, Ireland, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: Change from Baseline to Week 18). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.

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