Cannabidiol Gel for Fragile X Syndrome

Recruiting at 33 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Zynerba Pharmaceuticals, Inc.

Must not be taking: Investigational drugs

Disqualifiers: Pregnancy, Liver issues, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

550 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot participate if you are taking any investigational drugs or using experimental devices.

What data supports the effectiveness of the drug ZYN002 - Cannabidiol Transdermal Gel for Fragile X Syndrome?

Research suggests that cannabidiol (CBD) may help manage symptoms of Fragile X Syndrome (FXS) by improving social interaction, reducing anxiety, and addressing other behavioral issues. Studies have shown that CBD can positively affect emotional and behavioral symptoms in FXS, and the transdermal gel ZYN002 has been associated with improvements in social avoidance and irritability, especially in patients with high levels of FMR1 gene methylation. ^{1 2 3 4 5}

Is cannabidiol gel safe for humans?

Cannabidiol (CBD) gel, including ZYN002, has been studied for safety in humans, showing a good safety profile with few side effects reported. It is considered to have fewer side effects compared to other medications, making it a promising option for conditions like Fragile X Syndrome. ^{2 3 4 5 6}

How is the drug ZYN002 different from other treatments for Fragile X Syndrome?

ZYN002 is unique because it is a cannabidiol (CBD) gel applied to the skin, offering a non-invasive way to deliver CBD, which may help manage symptoms of Fragile X Syndrome. Unlike oral CBD treatments, this transdermal gel provides a different method of administration that could improve tolerability and adherence. ^{2 3 7 8 9}

Eligibility Criteria

This trial is for children and adolescents with Fragile X Syndrome who participated in previous ZYN002 studies. They must follow study rules, provide informed consent through parents/caregivers, and females of childbearing age need a negative pregnancy test. Those with certain ongoing health issues or high liver enzyme levels can't join.

Inclusion Criteria

You have already taken part in study ZYN2-CL-016 or Study Zyn2-CL-033.

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

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.

Exclusion Criteria

I am not pregnant, nursing, or planning to become pregnant and will use contraception during and for three months after therapy.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Parents/caregivers apply the ZYN002 gel twice daily for the 52-week treatment period

52 weeks

Monthly visits for safety assessments and questionnaires

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may continue treatment for up to 72 months with annual evaluations

Up to 72 months

Treatment Details

Interventions

• ZYN002 - Cannabidiol Transdermal Gel

Trial Overview The trial tests the long-term safety of ZYN002, a Cannabidiol Transdermal Gel applied to the skin for those with Fragile X Syndrome. Participants will use this gel twice daily for one year to see how well they tolerate it over time.

Participant Groups

Group I: ZYN002 Experimental Treatment 1 Intervention

ZYN002 - cannabidiol Transdermal Gel

Who Is Running the Clinical Trial?

Zynerba Pharmaceuticals, Inc.

Lead Sponsor

Trials

4

Recruited

1,000+

Findings from Research

In a study involving 20 children and adolescents with Fragile X syndrome, the transdermal CBD gel (ZYN002) was found to be well tolerated, with 85% of participants reporting only mild side effects and no serious adverse events.

The treatment led to significant reductions in anxiety and behavioral symptoms, as measured by various scales, indicating its potential efficacy for managing symptoms associated with Fragile X syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1/2, open-label assessment of the safety, tolerability, and efficacy of transdermal cannabidiol (ZYN002) for the treatment of pediatric fragile X syndrome. Heussler, H., Cohen, J., Silove, N., et al.[2020]

A narrative review and case series involving three patients with Fragile X syndrome (FXS) treated with oral CBD-enriched solutions showed functional benefits, including reduced anxiety and improved sleep and language skills.

The case series suggests that CBD may help manage symptoms of FXS, as two patients experienced a return of symptoms after stopping treatment, which improved again upon reintroduction of CBD, indicating its potential therapeutic role.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Fragile X Syndrome with Cannabidiol: A Case Series Study and Brief Review of the Literature. Tartaglia, N., Bonn-Miller, M., Hagerman, R.[2023]

The endocannabinoid system (ECS) plays a crucial role in neuronal development and cognitive function, and its dysregulation is linked to fragile X syndrome (FXS), which is caused by the absence of the FMR1 protein due to gene silencing.

Cannabidiol (CBD) shows promise as a treatment for FXS by potentially restoring synaptic balance and reducing receptor overstimulation, with clinical evidence from the CONNECT-FX trial indicating improvements in social behaviors in patients with high FMR1 gene methylation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of the endocannabinoid system in fragile X syndrome: potential mechanisms for benefit from cannabidiol treatment. Palumbo, JM., Thomas, BF., Budimirovic, D., et al.[2023]

In a study using Fmr1-knockout mice, CBDV showed limited effectiveness when administered during adulthood, only improving some acoustic responses and neurotrophin levels.

However, when given during adolescence, CBDV significantly prevented cognitive, social, and sensory issues in adult Fmr1-KO mice, suggesting that early treatment may be crucial for its therapeutic benefits in Fragile X syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Administration of the Phytocannabinoid Cannabidivarin Prevents the Neurobehavioral Abnormalities Associated with the Fmr1-KO Mouse Model of Fragile X Syndrome. Premoli, M., Fyke, W., Bellocchio, L., et al.[2023]

A qualitative survey of parents and caregivers revealed that many are using various forms and doses of cannabidiol (CBD) to treat symptoms of Fragile X Syndrome (FXS), citing its perceived benefits and fewer side effects compared to traditional medications.

Most respondents reported that CBD improved symptoms such as anxiety and hyperactivity in individuals with FXS, indicating its potential therapeutic value, although further research is needed to fully understand its effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parent and Caregiver Perspectives towards Cannabidiol as a Treatment for Fragile X Syndrome. Maertens, M., Silver, H., Dixon Weber, J., et al.[2022]

PTL101, an oral formulation of highly purified CBD, was found to be safe and well-tolerated in healthy volunteers, showing a significant increase in CBD absorption compared to the Sativex oromucosal spray.

The 10 mg dose of PTL101 demonstrated 134% bioavailability relative to the reference spray, indicating that it delivers CBD more effectively, which could make it a promising option for therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Dose Pharmacokinetics of Oral Cannabidiol Following Administration of PTL101: A New Formulation Based on Gelatin Matrix Pellets Technology. Atsmon, J., Heffetz, D., Deutsch, L., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Cannabidiol (CBD) reduces anxiety-related behavior in mice via an FMRP-independent mechanism. [2020]

2. England pubmed.ncbi.nlm.nih.gov

A phase 1/2, open-label assessment of the safety, tolerability, and efficacy of transdermal cannabidiol (ZYN002) for the treatment of pediatric fragile X syndrome. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Treatment of Fragile X Syndrome with Cannabidiol: A Case Series Study and Brief Review of the Literature. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Role of the endocannabinoid system in fragile X syndrome: potential mechanisms for benefit from cannabidiol treatment. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Early Administration of the Phytocannabinoid Cannabidivarin Prevents the Neurobehavioral Abnormalities Associated with the Fmr1-KO Mouse Model of Fragile X Syndrome. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Parent and Caregiver Perspectives towards Cannabidiol as a Treatment for Fragile X Syndrome. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Multiple sclerosis symptoms and spasticity management: new data. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Single-Dose Pharmacokinetics of Oral Cannabidiol Following Administration of PTL101: A New Formulation Based on Gelatin Matrix Pellets Technology. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Evidence for the efficacy and effectiveness of THC-CBD oromucosal spray in symptom management of patients with spasticity due to multiple sclerosis. [2020]