Trial Outcomes & Findings for Open-Label Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With 22q11.2 Deletion Syndrome (INSPIRE) (NCT NCT05149898)

This Phase 2, open-label study was conducted at 2 sites in Australia and 1 site in the United States between 19 February 2020 and 09 November 2022.

Data were collected as a single arm because, based on pharmacokinetics (PK) modeling, exposure is consistent between doses. The study protocol and statistical analysis plan (SAP) were not amended. Instead, the Sponsor has written a Note to File to state how data were collected.

Open-Label Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With 22q11.2 Deletion Syndrome (INSPIRE)

An adverse event (AE) is an undesirable medical occurrence or worsening of a pre-existing medical condition that occurs at any time after signing of the informed consent form whether or not it is considered to be related to treatment. Any AE that results in one or more of the following is considered a SAE: death, life threatening, in-patient hospitalization, persistent or significant disability/incapacity, congenital abnormality or birth defect, and other medically important events. TEAEs are defined as AEs with onset dates on or after the start of study drug. Adverse event data were collected as a single arm because, based on pharmacokinetics modeling, exposure is consistent between doses.

The Aberrant Behavior Checklist - Community (ABC-C) instrument is a scale for rating inappropriate and maladaptive behavior of participants with developmental disabilities, including intellectual disability and autism spectrum disorder. The ABC-C was completed by the parent/caregiver with support from the site staff. The ABC-C asks responders to rate behaviors from "0= not at all a problem" to "3= the problem is severe in degree" across 58 questions. The ABC-C consists of 5 subscales: hyperactivity noncompliance subscale (scale range from 0 to 48), irritability subscale (scale range from 0 to 45), inappropriate speech subscale (scale range from 0 to 12), stereotypic behavior subscale (scale range from 0 to 21) and social withdrawal subscale (scale range from 0 to 48). Total scores range from 0 (not at all a problem) to 174 (the problem is severe in degree). Higher scores indicate higher severity. Baseline was defined as the last assessment prior to the first dose of ZYN002.

The Anxiety, Depression and Mood Scale (ADAMS) was completed by the parent/caregiver with support from the site staff. The ADAMS is comprised of 28 items (question 3 is counted in two subscales), which are rated on a scale of "0=not a problem" to "3=severe problem". The ADAMS consists of 5 subscales: depressed mood subscale (scale range from 0 to 21), general anxiety subscale (scale range from 0 to 21), manic/hyperactive behavior subscale (scale range from 0 to 15), obsessive/compulsive behavior subscale (scale range from 0 to 9) and social avoidance subscale (scale range from 0 to 21). Total score range is 0 to 84. Higher scores indicate higher severity/worse outcome. Baseline was defined as the last assessment prior to the first dose of ZYN002.

The Clinical Global Impression-Severity (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment relative to the clinician's past experience with participants who have the same diagnosis. Considering total clinical experience, a participant was assessed on severity of mental illness at the time of rating as follows: 1= normal, not at all ill; 2= borderline mentally ill; 3= mildly ill; 4= moderately ill; 5= markedly ill; 6= severely ill; or 7= extremely ill. The CGI-S score range from 0 (not a problem) to 7 (severe problem). Higher scores indicate higher severity. Baseline was defined as the last assessment prior to the first dose of ZYN002.

The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1= very much improved; 2= much improved; 3= minimally improved; 4= no change; 5= minimally worse; 6= much worse; or 7= very much worse. Baseline was defined as the last assessment prior to the first dose of ZYN002. Higher scores indicate worse outcome.

The parent/caregiver was asked the following question "What are the three behavioral, emotional, or social problems that most impacted your son/daughter and his/her family in approximately the past year?". At each study visit the parent/caregiver was reminded of their responses from the screening visit in order to rate the 3 questions for improvement or worsening.

The Pediatric Anxiety Rating Scale-Revised (PARS-R) is a clinician-rated caregiver interview that covers 61 behaviors related to anxiety. The interviewer assesses 7 items: overall severity of anxiety feelings; overall number, frequency, and severity of anxiety symptoms; overall severity of anxiety (physical symptoms); overall avoidance of anxiety-provoking situations; and anxiety interference with family and peer relationships and/or performance at home or outside of the home. Each of the 7 severity items was scored on a scale of 1 to 5, with 5 being the most severe and frequent. The total score for the PARS-R is the sum of the 7 items; range from 0 (not a problem) to 35 (severe problem). Higher scores indicate higher severity. Baseline was defined as the last assessment prior to the first dose.

Blood samples were collected to determine the plasma concentrations of cannabidiol and Δ9-tetrahydrocannabinol.