Cannabidiol Gel for Fragile X Syndrome

(RECONNECT Trial)

Not currently recruiting at 41 trial locations

Overseen By Kristen Kaplan

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Zynerba Pharmaceuticals, Inc.

Must be taking: Antiseizure, Psychoactive

Must not be taking: Cannabis, Benzodiazepines, CYP3A4 drugs

Disqualifiers: Pregnancy, Drug abuse, Cardiovascular disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 9

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a gel made with cannabidiol (CBD) to determine its effectiveness for people with Fragile X Syndrome (FXS), a genetic condition that can cause learning and behavioral challenges. The study aims to assess the safety and effectiveness of this CBD gel compared to a placebo gel (a substance with no active drug). Participants will receive either the CBD gel or the placebo over an 18-week period. Those with a confirmed genetic diagnosis of FXS and stable medical routines might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment validation.

Will I have to stop taking my current medications?

The trial requires that participants maintain a stable regimen of psychoactive medications and anti-seizure medications if they are already on them. However, certain medications like cannabis products, specific anti-seizure drugs, and strong CYP3A4 inhibitors or inducers must be stopped before joining the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ZYN002, a CBD gel applied to the skin, has undergone safety testing in people. One study tested participants' tolerance to ZYN002, and many tolerated it well, though some experienced mild side effects, such as redness at the application site. Another study observed long-term use of the gel and found no major safety concerns. The FDA has recognized CBD, the main ingredient in ZYN002, for its potential benefits, indicating that the treatment is safe enough for further testing in people. ^{1 2 3 4 5}

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

Unlike standard treatments for Fragile X Syndrome, which often include behavioral therapies and medications like antipsychotics and antidepressants, ZYN002 is unique because it uses cannabidiol (CBD) as an active ingredient. This treatment is delivered through a transdermal gel, meaning it's applied to the skin, allowing for a non-invasive and potentially more consistent delivery of CBD. Researchers are excited about ZYN002 because CBD may offer therapeutic benefits without the side effects commonly associated with traditional medications, providing a novel approach to managing symptoms of Fragile X Syndrome.

What evidence suggests that ZYN002 - CBD transdermal gel might be an effective treatment for Fragile X Syndrome?

Research has shown that ZYN002, a CBD gel applied to the skin, may help treat Fragile X Syndrome (FXS). In the CONNECT-FX study, this gel was tested on individuals with FXS and positively affected their behavior. The gel is unique because it contains CBD without any THC, avoiding the "high" often associated with cannabis. Another study, where participants continued using the gel, found it safe and effective over time. In this trial, participants will receive either the ZYN002 transdermal gel or a placebo gel. These findings suggest that ZYN002 could be a helpful treatment for managing symptoms in people with FXS. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for children, adolescents, and young adults aged 3 to less than 23 with Fragile X Syndrome. Participants must be in good health, have a stable regimen of medications if taking any, and not use cannabis products. Girls who can have babies must test negative for pregnancy.

Inclusion Criteria

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.

I am between 3 and 17 years old.

I've been on a stable dose of up to 3 psychoactive medications for at least 4 weeks.

Exclusion Criteria

You answered "yes" to Question 4 or 5 on the Children's Columbia-Suicide Severity Rating Scale during screening or at any time during the study.

I am taking medication for seizures or epilepsy.

I am not pregnant, nursing, or planning to become pregnant and agree to use effective birth control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive ZYN002 or placebo transdermal gel for 18 weeks

18 weeks

7 visits (combination of in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (telephone follow-up)

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• ZYN002 - CBD transdermal gel
• ZYN002 - transdermal gel

Trial Overview The study tests the safety and effectiveness of a Cannabidiol gel (ZYN002) compared to a placebo over an 18-week period. It's randomized and double-blind, meaning neither the researchers nor participants know who gets the real treatment or placebo.

How Is the Trial Designed?

Group I: ZYN002 - transdermal gel Experimental Treatment 1 Intervention

Pharmaceutically manufactured. Cannabidiol is formulated as a clear gel for transdermal delivery.

Group II: Placebo transdermal gel Placebo Group 1 Intervention

Placebo is formulated as a clear gel for transdermal delivery.

Who Is Running the Clinical Trial?

Zynerba Pharmaceuticals, Inc.

Lead Sponsor

Trials

4

Recruited

1,000+

Published Research Related to This Trial

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]

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 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]

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]

In a study involving 34 children aged 4-10 with Dravet syndrome, purified cannabidiol (CBD) was found to be generally well-tolerated, with a dose-proportional increase in exposure to CBD and its metabolites, indicating effective pharmacokinetics.

While CBD treatment resulted in more adverse events (AEs) compared to placebo, such as pyrexia and sedation, no significant safety concerns were identified, and all patients recovered from any elevated liver enzymes without meeting criteria for drug-induced liver injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. Devinsky, O., Patel, AD., Thiele, EA., et al.[2022]

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]

In a study involving 17 healthy adults, different doses of oral cannabidiol (CBD) did not impair driving performance, as measured by standard deviation of lateral position (SDLP), suggesting that CBD is safe for driving tasks.

CBD did not induce feelings of intoxication or impair cognitive function, indicating its potential for safe use in everyday activities, including driving, even at higher doses like 1500 mg.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of cannabidiol on simulated driving and cognitive performance: A dose-ranging randomised controlled trial. McCartney, D., Suraev, AS., Doohan, PT., et al.[2023]

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]

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 ... ZYN002 is the first-and-only pharmaceutically manufactured synthetic cannabidiol devoid of THC and formulated as a patent-protected permeation- ...

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. 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 ...