Cannabidiol Gel for Fragile X Syndrome

Enrolling by invitation at 34 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a gel containing cannabidiol (a compound from cannabis that doesn't cause a high) to determine its effectiveness for individuals with Fragile X Syndrome, a genetic condition that can lead to learning challenges and social and behavioral issues. The gel, known as ZYN002, is applied to the skin on the shoulders or upper arms twice daily. It is intended for those who have participated in earlier related studies and are willing to adhere to all study rules. Participants' parents or caregivers must assist with the application and ensure compliance with the study guidelines. As a Phase 2/3 trial, this study measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to important research.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that ZYN002, a gel containing cannabidiol applied to the skin, is generally safe. Studies have followed users for up to 45 months, and the gel is usually well-tolerated. Some users reported mild skin irritation at the application site, but serious side effects are rare.

In another study, using the gel for Fragile X Syndrome did not cause any unexpected safety issues. This finding suggests the gel is safe for long-term use in these patients. Overall, the research supports ZYN002 as a safe treatment option for Fragile X Syndrome when used as directed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Fragile X Syndrome?

Unlike traditional treatments for Fragile X Syndrome, which often include medications like antipsychotics or antidepressants to manage symptoms, ZYN002 is a cannabidiol transdermal gel that offers a novel approach. Researchers are excited about ZYN002 because it leverages cannabidiol, a compound derived from cannabis, which is believed to help with behavioral symptoms by interacting with the endocannabinoid system in the brain. Additionally, the transdermal delivery method is unique, as it allows the medication to be absorbed through the skin, potentially minimizing systemic side effects and offering a more consistent release of the active ingredient. This innovative approach could provide a more targeted and gentle option for managing symptoms associated with Fragile X Syndrome.

What evidence suggests that this treatment might be an effective treatment for Fragile X Syndrome?

Research has shown that ZYN002, a gel containing cannabidiol (a substance from the cannabis plant), may help treat Fragile X syndrome. One study found that ZYN002 was safe and improved some behaviors in patients. However, the RECONNECT Study did not achieve its main goal of significantly improving symptoms. Despite this, participants generally tolerated the gel well, with mild pain at the application site as the most common side effect. These mixed results suggest some potential, but more research is needed to fully understand the gel's effectiveness for Fragile X syndrome. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. neurology.org neurology.org/doi/10.1212/WNL.0000000000209008

Update to Open-Label Extension Study (ZYN2-CL-017) ... Objective: To assess the long-term safety and effectiveness of ZYN002, a pharmaceutically produced transdermal cannabidiol gel in development ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36434514/

A randomized, controlled trial of ZYN002 cannabidiol ... CONNECT-FX was a double-blind, randomized phase 3 trial assessing efficacy and safety of ZYN002, transdermal cannabidiol gel, for the treatment of behavioral ...

3. ir.harmonybiosciences.com ir.harmonybiosciences.com/news-releases/news-release-details/harmony-biosciences-provides-update-its-phase-3-reconnect-study

Harmony Biosciences Provides Update From Its Phase 3 ... ... trial (the RECONNECT Study) of ZYN002 in Fragile X syndrome (FXS). The RECONNECT Study did not meet the primary endpoint of improvement in ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04977986

NCT04977986 | Clinical Study of Cannabidiol in Children ... This is a randomized, double-blind, placebo-controlled, multiple-center study, to assess the efficacy and safety of Cannabidiol administered as ZYN002

5. neurologylive.com neurologylive.com/view/zyn002-gel-shows-long-term-safety-behavioral-improvements-fragile-x-syndrome

ZYN002 Gel Shows Long-Term Safety and Behavioral ... ZYN002 demonstrated a favorable safety profile in patients with Fragile X syndrome, with application site pain as the most common adverse event.

6. jaacap.org jaacap.org/article/S0890-8567(23)01999-8/fulltext

Long-Term Safety and Sustained Efficacy of ZYN002 ... Safety data in all patients, up to 45 months, and efficacy data through 24 months in patients with 100% fragile X messenger ribonucleoprotein 1 (FMR1) gene ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03802799

NCT03802799 | Open Label Extension to Assess the Long- ... 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 ...

8. jneurodevdisorders.biomedcentral.com jneurodevdisorders.biomedcentral.com/articles/10.1186/s11689-022-09466-6

A randomized, controlled trial of ZYN002 cannabidiol ... CONNECT-FX was a double-blind, randomized phase 3 trial assessing efficacy and safety of ZYN002, transdermal cannabidiol gel, for the treatment of behavioral ...