Zynerba Pharmaceuticals Inc has announced the initiation of a pivotal, multinational randomized, double-blind, placebo-controlled, multiple-center (RECONNECT) Phase 3 trial to evaluate the efficacy and safety of Zygel (cannabidiol formulated in a transdermal gel) in children and adolescents with Fragile X syndrome (FXS).
The company said the trial is planned to confirm the positive results observed in a population of responders in its CONNECT-FX trial, a randomized, double-blind, placebo-controlled trial that assessed the efficacy and safety of Zygel as a treatment for the behavioral symptoms of FXS.
FXS is a genetic condition that causes intellectual disability, behavioral and learning challenges, and is the most commonly known single-gene cause of autism spectrum disorder.
READ: Zynerba presents longer-term tolerability and efficacy data of Zygel in children and adolescents with autism spectrum disorder
“The RECONNECT trial provides us with an opportunity to confirm the positive results observed in a population of responders in our CONNECT-FX trial and further demonstrate the effect of Zygel on behaviors associated with FXS,” said Zynerba CEO Armando Anido in a statement.
“A significant unmet medical need continues to exist for therapeutics to treat patients with FXS. If successful, we believe the study could serve as the basis for Zygel approval in the U.S. for patients with FXS.”
Dr. Caroline Buchanan, an investigator in the RECONNECT trial, noted that children with FXS exhibit a number of developmental and behavioral symptoms including anxiety, social avoidance, hyperactivity, and socially unresponsive behaviors that significantly impact the family and the child’s capacity to interact with them, their peers, and care providers.
“Potentially having an approved treatment option for these vulnerable patients would be a significant step forward for FXS patients and their families,” she said.
Zynerba said RECONNECT will be an 18-week trial that is expected to enroll about 200 children and adolescents, aged three through 17 years, at approximately 25 clinical sites in the US, Australia, the UK, and Ireland.
About 160 of the patients enrolled will have complete (100%) methylation of their FMR1 gene and approximately 40 patients will have partial methylation of their FMR1 gene. Patients will be randomized 1:1 to either Zygel or placebo. Randomization will be stratified by gender, methylation status, and weight.
The company said the primary endpoint for the trial will be the change from baseline to the end of the treatment period in the Aberrant Behavior Checklist-Community FXS Specific (ABC-CFXS) Social Avoidance subscale in patients who have complete methylation of their FMR1 gene. The ABC-CFXS Social Avoidance subscale is the same primary endpoint used in the CONNECT-FX trial.
Key secondary efficacy endpoints include:
- The change from baseline to the end of the treatment period in the ABC-CFXS Irritability subscale in patients who have complete methylation of their FMR1 gene.
- Percent of patients with any improvement on the Caregiver Global Impression of Change (CaGI-C) at the end of the treatment period for Social Interactions among patients with complete methylation of the FMR1 gene.
- Percent of patients rated as improved on the Clinical Global Impression-Improvement (CGI-I) scale among patients with complete methylation (100%) of the FMR1 gene.
- The change from baseline to the end of the treatment period in the ABC-CFXS Social Avoidance subscale among all randomized patients (complete and partial methylation of the FMR1 gene).
Zynerba said topline results for the RECONNECT trial are expected in the second half of 2023.
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