Zynerba Starts Pivotal Trial of ZYN002, Investigational Cannabidiol Gel for Fragile X Treatment

Zynerba Pharmaceuticals has launched a pivotal Phase 3 clinical trial, called CONNECT-FX, that will assess the safety and effectiveness of its cannabis-based ZYN002 as a potential therapy to treat behavioral symptoms in patients with fragile X syndrome.

Top-line results from the trial are expected in the second half of 2019.

ZYN002 is administered as a gel through the skin once or twice daily, allowing its direct absorption from the skin into the blood. This direct formulation allows patients to use lower doses than a pill, and minimizes the risk of side effects.

“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,” Armando Anido, chairman and CEO of Zynerba, said in a press release.

“We look forward to demonstrating the clinical effects of ZYN002 in treating some of the most common behavioral symptoms of Fragile X syndrome. 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,” he said.

The CONNECT-FX study will enroll approximately 200 children and adolescents, ages 3-17 years, diagnosed with fragile X, who carry a full mutation of the FMR1 gene, from approximately 20 locations in the U.S., Australia, and New Zealand.

Participants will be randomized to treatment with ZYN002 (one of two doses) or a placebo, after classification by gender, weight, and investigator geographic region.

At the end of dosing, a 12-month extension study will be conducted, where all patients will receive the treatment.

The study’s primary objective is to assess changes from the beginning of the trial, or baseline, up to the end of the treatment period using the Aberrant Behavior Checklist-Community FXS Specific (ABC-C_FXS) Social Avoidance subscale. The ABC-C is a 58-item rating scale used to assess maladaptive behaviors including irritability, hyperactivity, lethargy/withdrawal, repetitive acts, and inappropriate speech.

Secondary goals include measuring changes 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 accordance with recent guidance from the U.S. Food and Drug Administration, additional qualitative data on the clinical relevance of various fragile X behaviors to caregivers and patients will also be collected to capture the voice of patients in therapy development.

“Children with Fragile X syndrome are dramatically impacted by this genetic condition and its debilitating behavioral and emotional challenges, including anxiety, social withdrawal, irritability, inattention and aggression,” said Elizabeth M. Berry-Kravis, MD, PhD, professor of pediatrics, neurological sciences and biochemistry at Rush University Medical Center.

“In patients with Fragile X, augmentation of endogenous cannabinoid availability has the potential to positively impact social avoidance behaviors and anxiety during social interactions,” she said.

Results from an open-label Phase 2 trial found that ZYN002 improved core behavioral symptoms of fragile X syndrome, which were sustained through 38 weeks of treatment.

The FDA granted orphan drug status to ZYN002 as a potential fragile X treatment in 2016.

Zynerba expects the results to support the filing of a new drug application with the FDA for ZYN002 to treat fragile X. At this time, the U.S. has no approved therapies for the disease.