Zynerba, the company developing the gel — which is placed on the skin of the shoulder or upper arm — said topline results from the Phase 2/3 trial are planned by the end of the second quarter of 2020. If positive, Zynerba expects to file a request in the second half of 2020 for Zygel’s regulatory approval in the U.S. That approval could potentially be granted by mid-2021, the company said.
In total, 178 fragile X patients — 135 boys (76%), mean age 9.6 years — have already been dosed, with 15 more awaiting dosing. The study (NCT03614663) is ongoing at multiple sites in the U.S., Australia, and New Zealand. Its goal is to recruit 204 participants, ages 3-17, who are moderately to severely impacted due to fragile X .
For more information about the study’s contacts, locations, and inclusion criteria please visit here.
“We are nearing completion of enrollment in our pivotal CONNECT-FX study in patients with Fragile X syndrome, and we expect to report results from this trial late in the second quarter of 2020,” Armando Anido, chairman and CEO of Zynerba, said in a press release.
Evidence suggests that behavioral abnormalities in people with fragile X and other neurological conditions are linked to problems in the endocannabinoid system, which plays a key role in nerve cell communication and protection against damage. CBD — a naturally occurring chemical found in cannabis that does not get users “high” — is being investigated as a potential therapy for modulating the endocannabinoid system.
Zygel is engineered to deliver controlled amounts of CBD into the bloodstream through the skin.
The FAB-C trial enrolled 20 participants with fragile X, between ages 6 and 17, who received Zygel twice daily for 12 weeks as an add-on therapy. During the first six weeks, the researchers tested increasing doses of the gel, ranging from 50 mg up to 250 mg daily. From week 7, participants received Zygel at a stable dose — the highest tolerated dose given during the first six weeks.
Those results showed that Zygel was well-tolerated and led to clinically meaningful easing of anxiety and other behavioral symptoms in children and teenagers with fragile X.
Importantly, the participants in CONNECT-FX have more severe symptoms than those who took part in the FAB-C trial.
These fragile X patients have worse scores in the six subscales of the Aberrant Behavior Checklist-Community FXS Specific. That scale measures social avoidance, irritability, hyperactivity, being socially unresponsive, stereotypy (purposeless, repetitive movements), and inappropriate speech.
Participants in CONNECT-FX will be randomly assigned to treatment with Zygel or to a placebo. The daily doses of Zygel and placebo depend on the participants’ weight, with two sachets given those weighing 35 kg (about 77 pounds) or less, and four sachets administered to participants over 35 kg.
The study’s primary goal is to determine changes in social avoidance after 14 weeks of treatment compared with the behaviors at the start of the trial.
“We believe that the prospective inclusion criteria have enabled us to execute on a rigorous clinical trial of Zygel in a more severely impacted population of children and adolescents than included in our Phase 2 FAB-C study, which should enhance the study’s ability to demonstrate a strong signal of activity and minimize response variability,” Anido said.
Zynerba also is testing Zygel as a potential treatment for children and adolescents with autism spectrum disorder (ASD). The company announced it achieved its enrollment target of 36 patients in its Phase 2 BRIGHT trial (ACTRN12619000216112). Topline results of that study also are expected in the second quarter of 2020.
“With key milestones expected from each of our clinical programs in the first half of this year, 2020 has the potential to be a compelling and exciting year,” Anido said.
CONNECT-FX participants who successfully complete the study may have the opportunity to continue to receive Zygel in an open label extension trial. During trial screening, caregivers are informed of this opportunity, which is allowed regardless of their child’s perceived response or actual treatment assignment in CONNECT-FX.
To date, 96% of the 141 participants who have completed CONNECT-FX have enrolled in the open label extension trial (NCT03802799), the company said.