Fragile X SyndromePhase 2/3NCT03802799
Open Label Extension to Assess the Long-Term Safety and Tolerability of ZYN002 in Children and Adolescents With FXS
A Phase 2/3 study testing ZYN002 - Cannabidiol Transdermal Gel in people with Fragile X Syndrome, run by Zynerba Pharmaceuticals, Inc. at 26 sites in 4 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 3 to 29 years
- Conditions the study is for
- Fragile X Syndrome
- What is being tested?
- ZYN002 - Cannabidiol Transdermal Gel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 476 participants
- Where
- 26 sitesin 4 countries
- Study dates
- 9 Nov 2018to 30 Jun 2026
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
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
- 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
Who cannot join
- 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.
Trial locations and contacts
26 sites in 4 countries.
26 sites in 4 countries
United States19 sites
Han Phan
Atlanta, Georgia, 30329
Kennedy Krieger Institute
Baltimore, Maryland, 21205
Boston Children's Hospital
Boston, Massachusetts, 02115
Rush University Medical Center
Chicago, Illinois, 60612
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Science 37
Culver City, California, 90230
Children's Hospital of Colorado
Denver, Colorado, 80045
Greenwood Genetic Center
Greenville, South Carolina, 29605
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
Amnova Clinical Research, LLC
Irvine, California, 92604
University of Mississipi Medical Center
Jackson, Mississippi, 39216
University of Miami
Miami, Florida, 33136
Masonic Institute of Developing Brain
Minneapolis, Minnesota, 55414
The Fragile X Spectrum Disorder Clinic at Icahn School of Medicine at Mount Sinai, Division of Medical Genetics
New York, New York, 10029
Southwest Autism Research and Resource Center
Phoenix, Arizona, 85006
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 Research Institute
Washington D.C., District of Columbia, 20010
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
United Kingdom3 sites
Children's Clinical Research Facility, Royal Hospital for Children and Young People
Edinburgh, Lothian, EH105HF
Research Space
Leicester, Leicestershire, LE15WW
Manchester University NHS Foundation Trust
Manchester, M13 9WL
About this study
Official title: An Open-Label Extension Study to Assess the Long-Term Safety and Tolerability of ZYN002 Administered as a Transdermal Gel to Children, Adolescents, and Young Adults 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.
Read the 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.
- Conditions
- Fragile X Syndrome
- Being tested
- ZYN002 - Cannabidiol Transdermal Gel
- 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.
ZYN002 - Cannabidiol Transdermal GelDrug
Also called Cannabidiol Transdermal Gel
Pharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery)
| Study group | Role | What they receive |
|---|---|---|
| ZYN002 | Experimental | ZYN002 - cannabidiol Transdermal Gel Receives: Drug: ZYN002 - Cannabidiol Transdermal Gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 96 month.
Secondary outcomes (1)
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.
Measured: Change from baseline to end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2019
- Study start9 Nov 2018
- Primary completion30 Jun 2026 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Fragile X SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open-Label
- Masking
- None (open label)
- Enrolment
- 476 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zynerba Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03802799
- Sponsor's protocol ID
- ZYN2-CL-017
- Status last verified
- May 2026
- First submitted
- 26 Dec 2018
- Last updated
- 27 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Berry-Kravis E, Hagerman R, Cohen J, Budimirovic D, Buchanan CB, Silove N, Tich N, Thibodeau A, Dobbins T, Sebree T, O'Quinn S, Albers DS, Bzdek KG, Nomikos G, Budur K. Long-term safety and tolerability of transdermal cannabidiol gel in children and adolescents with Fragile X syndrome (ZYN2-CL-017): an interim analysis of an ongoing open-label extension study. J Neurodev Disord. 2025 Nov 18;17(1):69. doi: 10.1186/s11689-025-09657-x.
PubMed 41254489Heussler 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.
PubMed 33395098
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Extension Study to Assess the Long-Term Safety and Tolerability of ZYN002 Administered as a Transdermal Gel to Children, Adolescents, and Young Adults With Fragile X Syndrome
- ClinicalTrials.gov ID
- NCT03802799
- Acronym / sponsor ID
- ZYN2-CL-017
- Conditions
- Fragile X Syndrome
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 476 participants (actual)
- Lead sponsor
- Zynerba Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 9 Nov 2018 (actual)
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 14 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-Label
| Arm | Type | Receives |
|---|---|---|
| ZYN002 | Experimental | Drug: ZYN002 - Cannabidiol Transdermal GelZYN002 - cannabidiol Transdermal Gel |
Who may qualify
- Ages
- 3 to 29 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZYN002 - Cannabidiol Transdermal GelAlso: Cannabidiol Transdermal GelPharmaceutically manufactured. Cannabidiol formulated as a clear gel (transdermal delivery) | Drug | ZYN002 |
Primary outcome
To evaluate the long-term safety and tolerability of ZYN002 administered as a transdermal gel formulation.
Time frame: Up to 96 month.
Safety assessment will include collection of any treatment emergent adverse events
1 secondary outcome
To evaluate the long-term efficacy of ZYN002 in the treatment of symptoms of FXS.
Time frame: Change from baseline to end of treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2026.
- Derived from this study: PubMed 41254489Berry-Kravis E, Hagerman R, Cohen J, Budimirovic D, Buchanan CB, Silove N, Tich N, Thibodeau A, Dobbins T, Sebree T, O'Quinn S, Albers DS, Bzdek KG, Nomikos G, Budur K. Long-term safety and tolerability of transdermal cannabidiol gel in children and adolescents with Fragile X syndrome (ZYN2-CL-017): an interim analysis of an ongoing open-label extension study. J Neurodev Disord. 2025 Nov 18;17(1):69. doi: 10.1186/s11689-025-09657-x.
- Derived from this study: PubMed 33395098Heussler 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
26 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing ZYN002 - Cannabidiol Transdermal Gel in people with Fragile X Syndrome, run by Zynerba Pharmaceuticals, Inc. at 26 sites in 4 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 5 inclusion and 4 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: under way, not looking for participants, as of the sponsor's last update on 27 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United States, Australia, United Kingdom, 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
This study is still under way. Results are not available in the source record yet.
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?
To evaluate the long-term safety and tolerability of ZYN002 administered as a transdermal gel formulation. (time frame: Up to 96 month.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03802799, which also lists 2 linked publications.
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 27 May 2026.