Patients Ages 3–17 Sought for Large-Scale Trial Testing CBD Gel Zygel

Yedida Y Bogachkov PhD avatar

by Yedida Y Bogachkov PhD |

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Zynerba Pharmaceuticals is recruiting children and adolescents with fragile X syndrome for a large-scale clinical trial testing the safety and efficacy of the cannabidiol (CBD) gel Zygel for treating behavioral problems.

The Phase 3 trial, called RECONNECT, is enrolling participants ages 3—17 at 26 sites across the U.S., Australia, the U.K., and Ireland. More information on contacts and locations can be found here.

“If successful, we believe the study could serve as the basis for Zygel approval in the US for patients with [fragile X syndrome],” Armando Anido, chairman and CEO of Zynerba, said in a press release.

Top-line results are expected in the second half of 2023.

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Zygel is a gel, applied to the shoulder or upper arm, that’s designed to deliver controlled amounts of a purified form of cannabidiol (CBD) into the bloodstream through the skin. CBD is the major non-psychoactive cannabinoid (active component) in the cannabis or marijuana plant. It mimics the body’s natural cannabinoids that modulate the endocannabinoid system.

Problems in the endocannabinoid system have been linked to some behavioral abnormalities that characterize fragile X. As such, Zygel is expected to lessen behavioral symptoms in this patient population.

The trial (NCT04977986) is expected to enroll about 200 patients, most of whom will have a complete methylation of FMR1, the gene mutated in fragile X.

DNA methylation is a biochemical modification that “turns genes off,” and a complete methylation of FMR1 is associated with a total absence of the FMRP protein and greater disease severity.

The Phase 3 trial will randomly assign patients to receive either Zygel — with the dosage dependent on body weight — or a placebo for an 18-week (about 4.5 months) treatment period. Treatment primarily will consist of a screening visit followed by seven additional sessions, conducted both on-site and virtually.

Blood samples will be collected for a safety analysis of the gel. Surveys and questionnaires will be completed by the study’s doctors, as well as by patients and/or caregivers, all seeking to assess the efficacy and safety of Zygel.

The trial’s primary endpoint, or goal, is to evaluate whether Zygel can significantly ease behavioral symptoms among the children and teens in the study. Symptoms will be assessed by the Aberrant Behavior Checklist-Community FXS Specific (ABC-CFXS) Social Avoidance subscale, a validated measure of behavioral abnormalities common in fragile X.

The ABC-CFXS covers social avoidance, irritability, hyperactivity, and inappropriate speech.

A previous Phase 2/3 trial (NCT03614663), called CONNECT-FX, also evaluated the safety and effectiveness of Zygel treatment. That three-month trial compared Zygel with a placebo in 212 children and adolescents with fragile X.

Top-line data found the trial failed to meet both its main and secondary goals of significantly easing behavioral symptoms.

However, a subset of Zygel-treated patients showed statistically significant and clinically meaningful reductions in behavioral symptoms, compared with those given a placebo gel. This subset of children and teen had more than 90% methylation in the FMR1 gene and thus more severe behavioral symptoms.