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

NCT05149898 | Completed Phase 2 Results FDA Drug

• 1 other identifier: ZYN2-CL-031
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 3

Brief Summary

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).

Conditions

22Q11.2 Deletion Syndrome

Keywords

22qDS; Chromosome 22q11.2 deletion syndrome; DiGeorge syndrome; Velocardiofacial syndrome; Velo-cardio-facial syndrome (VCFS); CATCH22 syndrome; Conotruncal anomaly face syndrome (CTAF); Shprintzen syndrome; Autosomal dominant Opitz G/BBB syndrome; Cayler cardio facial syndrome

Outcome Measures

Primary Outcomes (1)

• 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.

  From first dose of study drug administration (Day 1) up to end of the study, approximately 306 days

Secondary Outcomes (7)

• Change From Baseline in Aberrant Behavior Checklist - Community (ABC-C) at Week 14 (Period 1) and Week 38 (Period 2)

  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)

  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)

  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)

  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)

  Period 1: Week 14 (Day 98 ± 3 days); Period 2: Week 38 (Day 266 ± 3 days).

Study Arms (1)

Open-label

EXPERIMENTAL

Open-label

Drug: ZYN002

Interventions

ZYN002 DRUG

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.

Also known as: Cannabidiol Transdermal Gel

Open-label

Eligibility Criteria

• Age: 4 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female children and adolescents aged 4 to less than 18 years, at the time of Screening.
• Judged by the Investigator to be in generally good health at Screening based upon the results of a medical history, physical examination, and clinical laboratory test results.
• Participants must have a diagnosis of 22qDS confirmed by genetic testing.
• Participants have a Clinical Global Impression-Severity (CGI-S) score of 4 or higher at Screening and Visit 2.
• Participants must have a Pediatric Anxiety Rating Scale-Revised (PARS-R) severity score of 10 or higher at Screening and Visit 2.
• Participants with a history of seizure disorders must currently be receiving treatment with a stable regimen of one or two AEDs, or must be seizure-free for one year if not currently receiving AEDs.
• If participants are receiving non-pharmacological behavioral and/or dietary interventions, they must be stable for three months prior to Screening.
• The participant has demonstrated stable calcium levels for one year prior to Screening.
• Participants have a body mass index between 12-35 kg / m² (inclusive).
• Females of childbearing potential must have a negative pregnancy test at the Screening Visit and a negative pregnancy test at all designated study visits.
• Participants and parents/caregivers agree to abide by all study restrictions and comply with all study procedures.
• Participants and parents/caregivers must be adequately informed of the nature and risks of the study and give written informed consent (and assent if applicable) prior to Screening.
• Parents/caregiver(s) must provide written consent to assist in study drug administration.
• In the Investigator's opinion, participants and parents/caregivers are reliable and willing and able to comply with all protocol requirements and procedures.

You may not qualify if:

• Females who are pregnant, nursing, or planning a pregnancy; females of childbearing potential and male participants with a partner of childbearing potential who are unwilling or unable to use an acceptable method of contraception for the duration of therapy and for three months after the last dose of study medication.
• History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to any compound or chemical class related to ZYN002 or its excipients.
• Exposure to any investigational drug or device ≤ 30 days prior to Screening or at any time during the study.
• Participant has Alanine transaminase (ALT), Aspartate transaminase (AST), or total bilirubin levels ≥ 2 times the Upper limit of normal (ULN) or has alkaline phosphatase levels ≥ 3 times the ULN as determined from Screening safety laboratories.
• Use of cannabis or any Δ9-tetrahydrocannabinol (THC) or CBD-containing product within three months of Screening Visit or during the study.
• The participant has a positive drug screen.
• The participant is using the following AEDs: clobazam, phenobarbital, ethosuximide, felbamate, carbamazepine, phenytoin or vigabatrin.
• Participant is using any strong inhibitor/inducer of CYP3A4 or sensitive substrate for CYP3A4 including but not limited to the following medications: midazolam, oral ketoconazole, fluconazole, nefazadone, rifampin, alfentanil, alfuzosin, amiodarone, cyclosporine, dasatinib, docetaxol, eplerenone, ergotamine, everolimus, fentanyl, halofantrine, irinotecan, lapatinib, levomethadyl, lumefantrine, nilotinib, pimozide, quinidine, ranolazine, sirolimus, tacrolimus, temsirolimus, toremifene, tretinioin, vincristine, vinorelbine, St. John's Wort, and grapefruit juice/products.
• Participant with diagnosis of known genetic disorder, other than 22qDS.
• Participant has diagnosis of DiGeorge or Velocardiofacial syndrome without the presence of 22qDS.
• Participant has a primary psychiatric diagnosis other than 22qDS or anxiety, including bipolar disorder, psychosis, schizophrenia, Post traumatic stress disorder (PTSD) or major depressive disorder.
• Participant is on stable treatment of \>6 months of not more than two psychoactive medications at screening or throughout the study (with the exception of one psychoactive medication prescribed for sleep).
• Participant has an advanced, severe, or unstable disease that may interfere with the study outcome evaluations.
• Participant is expected to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study.
• Participant has an acute or progressive neurological disease, or any psychiatric disorder or severe mental abnormalities that are likely to require changes in drug therapy or interfere with the objectives of the study or ability to adhere to protocol requirements.

Sponsors & Collaborators

• Zynerba Pharmaceuticals, Inc.: collaborator
• Harmony Biosciences Management, Inc.: lead

Study Sites (3)

Greenwood Genetic Center

Greenville, South Carolina, 29605, United States

Location

Lady Cilento Children's Hospital - South Brisbane

Brisbane, Queensland, 4101, Australia

Location

Genetics Clinics Australia

Melbourne, Victoria, 3161, Australia

Location

MeSH Terms

Conditions

DiGeorge Syndrome

Condition Hierarchy (Ancestors)

22q11 Deletion Syndrome; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Lymphatic Abnormalities; Lymphatic Diseases; Hemic and Lymphatic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Hypoparathyroidism; Parathyroid Diseases; Endocrine System Diseases

Limitations and Caveats

Dosing was adjusted based on weight. Therefore, the decision was made to collect data as a single arm ("ZYN002") instead of by dose or by period because the dosing is not relevant to the interpretation of the study results and based on pharmacokinetic modeling, exposure is consistent across doses. The Protocol and Statistical Analysis Plan will not be updated. Instead, the Sponsor has written a Note to File to state how data were collected.

Results Point of Contact

• Title: Kristen Bzdek, MD
• Organization: Harmony Biosciences Management, Inc.

kbzdek@harmonybiosciences.com

484-539-9800

Study Officials

• Kristen Bzdek, MD

  Harmony Biosciences Management, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label study

Study Record Dates

• First Submitted: October 5, 2021
• First Posted: December 8, 2021
• Study Start: February 19, 2020
• Primary Completion: November 9, 2022
• Study Completion: November 9, 2022
• Last Updated: March 9, 2026
• Results First Posted: March 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); AU (2)