Presentation 18 – Dr Honey Heussler

SSBP Virtual Symposium 2023

An Open-Label Trial Assessing Short- and Long-Term Tolerability and Efficacy of ZYN002 (Cannabidiol) Administered as a Transdermal Gel to Children and Adolescents with 22q11.2 Deletion Syndrome (INSPIRE)

Presenting Author : Dr Honey Heussler

Abstract

An Open-Label Trial Assessing Short- and Long-Term Tolerability and Efficacy of ZYN002 (Cannabidiol) Administered as a Transdermal Gel to Children and Adolescents with 22q11.2 Deletion Syndrome (INSPIRE)

Heussler H.¹, Duhig M.¹, Cohen J.², Buchanan C.³, O’Neill C.⁴, O’Quinn S.⁴

¹Centre for Clinical Trials in Rare Neurodevelopmental Disorders, Children’s Health Queensland Hospital and Health Services, South Brisbane, Queensland, Australia
²Genetic Clinics Australia, North Caulfield, Victoria, Australia
³Greenwood Genetic Center, Greenville, SC, USA
⁴Zynerba Pharmaceuticals, Devon, PA, USA

Background: Behavioural problems and anxiety occur frequently in 22q11.2 deletion syndrome (22q). ZYN002 is a pharmaceutically produced cannabidiol transdermal gel. INSPIRE was an open-label, phase 2 trial evaluating safety/tolerability and efficacy of ZYN002 in individuals ages 4 to <18 years, in treating behavioural and anxiety-related symptoms in 22q.

Methods: Individuals having a Clinical Global Impression-Severity (CGI-S) score ≥4 and a Pediatric Anxiety Rating Score-Revised (PARS-R) score ≥10 were enrolled. Patients received 250 or 500 mg/day (weight-based) added to current therapy for 14 weeks (Period 1). Patients with ≥35% improvement in Aberrant Behavior Checklist-Community (ABC-C) Irritability at week 14 could continue for an additional 24 weeks (Period 2). Safety assessments included adverse events (AEs), vital signs, laboratories, and electrocardiograms (ECGs). Efficacy assessments included the PARS-R, Anxiety, Depression and Mood Scale (ADAMS), ABC-C and CGI-Improvement (CGI-I).

Results: Twenty patients, 60% males, mean age of 9.9 years enrolled. Seventeen patients completed Period 1 and 13 patients entered Period 2. Statistically significant improvements occurred in the PARS-R, ADAMS and ABC-C at Week 14. Percent improvement from baseline were PARS-R: Total Score 40.6%, p=0.0005; ADAMS: Total Score 45.3%, p=0.0005; General Anxiety 43.6%, p=0.0005; Depressed Mood 50.3%, p=0.0033; Social Avoidance 41.3%, p=0.0084; Obsessive/Compulsive Behaviour 64%, p=0.0037; Manic/Hyperactive Behaviour 38.2%, p=0.0032; and ABC-C: Social Withdrawal 27.6%, p=0.011; Inappropriate Speech 18.3%, p=0.0166; Stereotypic Behaviour 52.1%, p=0.0155; Irritability 36.3%, p=0.0055; Hyperactivity 16.5%, p=0.0091. Ten of 16 patients (62.5%) were “much improved” or “very much improved”. Improvements at Week 14 were sustained through Period 2. Over 38 weeks, 3 patients reported treatment related AEs, all mild application site events. One patient discontinued due to AEs not related to ZYN002. Four non-treatment-related serious AEs were reported. No clinically significant changes in vital signs, ECGs or laboratories were reported.

Conclusions: ZYN002 was well tolerated and improved behavioural and anxiety-related symptoms in 22q. Further studies are warranted.

Keywords: 22q11.2; anxiety, behavioural problems, cannabidiol

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