Longer-term Tolerability and Efficacy of ZYN002 Cannabidiol Transdermal Gel in Children and Adolescents with Autism Spectrum Disorder: An Open-label Phase 2 Study (BRIGHT [ZYN2-CL-030])

Background: ZYN002 is a pharmaceutically manufactured transdermal cannabidiol gel. BRIGHT is a single-center, open-label phase 2 study that evaluated the tolerability and efficacy of ZYN002 in children/adolescents aged 3-17 years with autism spectrum disorder (ASD). Data through 14 weeks were previously presented. The objective is to present longer-term data through 38 weeks of treatment with open label ZYN002.

Methods: Patients with Clinical Global Impression (CGI)–Severity scores ≥4 (moderate or greater) and Aberrant Behavior Checklist-Community (ABC-C) Irritability scores ≥18 were enrolled. Patients received ZYN002 250 or 500 mg/day on top of stable standard of care. Patients demonstrating ≥35% improvement in Irritability at week 14 were allowed to continue treatment. Safety assessments included adverse events (AEs), laboratory tests, and electrocardiograms (ECGs).

Results: 37 patients (mean age: 9.2 years) enrolled; 94% had moderate-to-severe symptoms; the mean baseline ABC-C Irritability score was 30.3. At week 14, significant improvements (P ≤0.0053) were observed for each ABC-C subscale, the Parent-Rated Anxiety Scale-ASD (PRAS-ASD) score, the Autism Parenting Stress Index (APSI) score and each Autism Impact Measure (AIM) domain in 28 who completed week 14. 57% of patients were improved (“much/very much improved”) based on CGI-Improvement (CGI-I). Eighteen patients demonstrated ≥ 35% improvement in Irritability and elected to continue. At week 38, improvements in the ABC-C subscale scores (50% to 61% across domains; P<0.0001), the PRAS-ASD (42%; P<0.0001), APSI (40%; P<0.0001) and the AIM (19% to 36% across domains; P≤0.0008) were maintained. 77% were improved on the CGI-I. 54% of patients reported AEs. AEs were mild (80%) or moderate (20%). Treatment-related AEs were reported in 19% of patients; most were mild and transient. One patient discontinued due to application site reaction. No serious or severe AEs or clinically significant changes in laboratory tests or ECGs were reported.

Conclusion: BRIGHT provides initial evidence suggesting a positive risk–benefit profile for ZYN002 when added on top of stable standard of care in children/adolescents with ASD which was maintained over 38 weeks. Further studies are warranted.