Study to Assess Safety & Efficacy of Cannabidiol in Children with Fragile X Syndrome

A genetic condition that typically affects males more than females, fragile X syndrome (FXS) is a rare disease caused by damage to the FMR1 gene located on the X chromosome, which, in turn, fails to produce the protein it typically makes. The rare disease is characterized by a host of neurological deficits, such as seizures, along with developmental, intellectual, and social disabilities.

Currently, there is no specific treatment for the disease; as such, management of the condition is usually more supportive rather than curative. However, now, a new pivotal clinical trial aims to evaluate the safety and efficacy of a cannabidiol (CBD) gel developed by Zynerba Pharmaceuticals to treat the debilitating behaviors associated with the disease.

The gel, dubbed ZYN002, will be evaluated in a multi-national randomized, double-blind, placebo-controlled, 14-week trial in children and adolescents with FXS. Unlike administration via oral form, transdermal delivery of ZYN002 allows for the drug to be absorbed through the skin to the bloodstream and avoids the potential gastrointestinal-associated adverse events by avoiding the GI tract.

Although CBD—a substance derived from marijuana—faces strict production and manufacturing regulations, the approval of a CBD oral solution for Lennox-Gastaut syndrome and Dravet syndrome by the US Food and Drug Administration (FDA) provides hope for ZYN002.

“We are excited to initiate CONNECT-FX, the first-of-its-kind clinical study evaluating transdermally delivered ZYN002 as a treatment for the debilitating behaviors associated with Fragile X syndrome,” said Armando Anido, chairman and chief executive officer of Zynerba, in a recent statement. “If successful, ZYN002 has the potential to become the first product indicated for the treatment of behavioral symptoms of Fragile X syndrome and help address the ongoing needs of the children and families impacted by this syndrome.”

The CONNECT-FX trial will enroll approximately 200 male and female patients with FXS who have a confirmed FMR1 gene full mutation spanning 20 clinical sites in the United States, Australia, and New Zealand. For the study, participants will be randomized 1:1 to receive either the investigative drug or placebo. Gender, weight, and investigator geographic region will dictate the randomization.

The change from baseline to the end of the treatment period in the Aberrant Behavior Checklist-Community FXS Specific (ABC-C_FXS) Social Avoidance subscale will serve as the primary endpoint for the trial. The secondary endpoints of the trial include change from baseline to the end of the treatment period in the ABC-C_FXS Irritability subscale score, the ABC-C_FXS Socially Unresponsive/Lethargic subscale score, and improvement in Clinical Global Impression—Improvement (CGI-I) at the end of the treatment period.

“In patients with Fragile X, augmentation of endogenous cannabinoid availability has the potential to positively impact social avoidance behaviors and anxiety during social interactions,” added Elizabeth M. Berry-Kravis, MD, PhD, professor of pediatrics, neurological sciences and biochemistry at Rush University Medical Center. “I am excited to participate in a double-blind placebo-controlled study of cannabidiol in Fragile X. I hope to be part of the effort to move what may be the first product indicated specifically for Fragile X syndrome toward availability for my patients.”

Zynerba will anchor the CGI-I scale to behavioral symptoms of FXS based recent discussions held with the FDA,

Further qualitative data on the clinical relevance of other FXS behaviors to caregivers and patients will also be gathered so as to remain consistent with recent guidance provided by the FDA on appropriately and accurately reflecting the patient voice throughout the drug’s development.

A meeting with the FDA to determine the acceptability of the trial data as the basis for a New Drug Application (NDA) filing will also be requested if positive results are gleaned from the trial. Top line results are expected in the second half of 2019.