To evaluate the safety and tolerability of ZYN002 administered as a transdermal gel formulation, for up to 38 weeks, in participants ages 4 to \<18 years, in the treatment of 22q.11.2 Deletion syndrome (22qDS).
This was an open-label study that assessed the safety, tolerability and efficacy of cannabidiol (CBD) administered as ZYN002, a transdermal gel, for the treatment of child and adolescent participants with 22qDS. Male and female participants with 22qDS were treated in Period 1 for 14 weeks. Participants that met study criteria were allowed to continue to Period 2 for an additional 24 weeks of treatment. At the end of the study, participants taking antiepileptic drug (AED) medication(s) had an additional one- or two-week Taper Period. Approximately 20 male and female participants, ages 4 to \< 18 years, received ZYN002.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Synthetic CBD (sCBD) Transdermal Gel pharmaceutically manufactured. sCBD formulated as a clear gel (transdermal delivery). Dose received is based on weight. 1. Participants who weigh ≤ 35 kilogram (kg) will receive 125 mg CBD Q12H (every 12 hours ± 2 hours); for a total daily dose of 250 mg CBD. 2. Participants who weigh \> 35 kg will receive 250 mg CBD Q12H (±2 hours) for a total daily dose of 500 mg CBD. Patients in both weight ranges ≤ 35 kg or \> 35 kg may receive an increased daily dose of 500 mg sCBDor 750 mg sCBD, respectively.
Greenwood Genetic Center
Greenville, South Carolina, United States
Lady Cilento Children's Hospital - South Brisbane
Brisbane, Queensland, Australia
Genetics Clinics Australia
Melbourne, Victoria, Australia
Overall Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs)
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.
Time frame: From first dose of study drug administration (Day 1) up to end of the study, approximately 306 days
Change From Baseline in Aberrant Behavior Checklist - Community (ABC-C) at Week 14 (Period 1) and Week 38 (Period 2)
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.
Time frame: Period 1: Baseline (Day 1) and Week 14 (Day 98 ± 3 days); Period 2: Week 14 (Day 98 ± 3 days) and Week 38 (Day 266 ± 3 days).
Change From Baseline in Anxiety, Depression and Mood Scale (ADAMS) at Week 14 (Period 1) and Week 38 (Period 2)
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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.
Time frame: Period 1: Baseline (Day 1) and Week 14 (Day 98 ± 3 days); Period 2: Week 14 (Day 98 ± 3 days) and Week 38 (Day 266 ± 3 days).Period 2: Baseline (Day 1 of
Change From Baseline in Clinical Global Impression-Severity (CGI-S) at Week 14 (Period 1) and Week 38 (Period 2)
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.
Time frame: Period 1: Baseline (Day 1) and Week 14 (Day 98 ± 3 days); Period 2: Week 14 (Day 98 ± 3 days) and Week 38 (Day 266 ± 3 days).
Number of Participants With Clinical Global Impression-Improvement (CGI-I) at Week 14 (Period 1) and Week 38 (Period 2)
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.
Time frame: Period 1: Week 14 (Day 98 ± 3 days); Period 2: Week 38 (Day 266 ± 3 days).
Number of Participants With Changes in Caregiver Reported Behavioral Problems at Week 14 (Period 1) and Week 38 (Period 2)
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.
Time frame: Period 1: Week 14 (Day 98 ± 3 days); Period 2: Week 38 (Day 266 ± 3 days).
Change From Baseline in Pediatric Anxiety Rating Scale-Revised (PARS-R) Total Severity Score at Week 14 (Period 1) and Week 38 (Period 2)
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.
Time frame: Period 1: Baseline (Day 1) and Week 14 (Day 98 ± 3 days); Period 2: Week 14 (Day 98 ± 3 days) and Week 38 (Day 266 ± 3 days).
Plasma Concentrations of Cannabidiol and Δ9-tetrahydrocannabinol
Blood samples were collected to determine the plasma concentrations of cannabidiol and Δ9-tetrahydrocannabinol.
Time frame: Week 14 (Day 98 ± 3 days) and Week 38 (Day 266 ± 3 days).