open-label study of zyn002 administered as a transdermal gel to children and adolescents with 22q11.2 deletion syndrome

Conditions: 22Q Deletion Syndrome

Summary: to evaluate the safety and tolerability of zyn002 administered as a transdermal gel formulation, for up to 38 weeks, in patients ages 4 to \< 18 years, in the treatment of 22q.11.2 deletion syndrome (22qds).

this is an open-label study to assess the safety, tolerability and efficacy of cannabidiol (cbd) administered as zyn002, a transdermal gel, for the treatment of child and adolescent patients with 22qds. male and female patients with 22qds will be treated in period 1 for 14 weeks. patients that meet study criteria will be allowed to continue to period 2 for an additional 24 weeks of treatment. at the end of study, patients taking antiepileptic drug (aed) medication(s) will have an additional one or two week taper period. approximately 20 male and female patients, ages 4 to \< 18 years, will receive zyn002.

Eligibility criteria:
inclusion criteria: 1. male or female children and adolescents aged 4 to less than 18 years, at the time of screening. 2. 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. 3. patients must have a diagnosis of 22q deletion syndrome (22qds) confirmed by genetic testing. 4. patients have a clinical global impression-severity (cgi-s) score of 4 or higher at screening and visit 2. 5. patients must have a pediatric anxiety rating scale-revised (pars-r) severity score of 10 or higher at screening and visit 2. 6. patients 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. 7. if patients are receiving non-pharmacological behavioral and/or dietary interventions, they must be stable for three months prior to screening. 8. patient has demonstrated stable calcium levels for one year prior to screening. 9. patients have a body mass index between 12-35 kg / m2 (inclusive). 10. females of childbearing potential must have a negative pregnancy test at the screening visit and a negative pregnancy test at all designated study visits. 11. patients and parents/caregivers agree to abide by all study restrictions and comply with all study procedures. 12. patients 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. 13. parents/caregiver(s) must provide written consent to assist in study drug administration. 14. in the investigator's opinion, patients and parents/caregivers are reliable and willing and able to comply with all protocol requirements and procedures. exclusion criteria: 1. females who are pregnant, nursing, or planning a pregnancy; females of childbearing potential and male patients 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. 2. history of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to any compound or chemical class related to zyn002 or its excipients. 3. exposure to any investigational drug or device ≤ 30 days prior to screening or at any time during the study. 4. patient has alt, ast, or total bilirubin levels ≥ 2 times the uln)or has alkaline phosphatase levels ≥ 3 times the uln as determined from screening safety laboratories. 5. use of cannabis or any thc or cbd-containing product within three months of screening visit or during the study. 6. patient has a positive drug screen. 7. patient is using the following aeds: clobazam, phenobarbital, ethosuximide, felbamate, carbamazepine, phenytoin or vigabatrin. 8. patient 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. 9. patient with diagnosis of known genetic disorder, other than 22qds. 10. patient has diagnosis of digeorge or velocardiofacial syndrome without the presence of 22qds. 11. patient has a primary psychiatric diagnosis other than 22qds or anxiety, including bipolar disorder, psychosis, schizophrenia, ptsd or major depressive disorder. 12. patient 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). 13. patient has an advanced, severe, or unstable disease that may interfere with the study outcome evaluations. 14. patient is expected to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study. 15. patient 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. 16. patient has a positive result for the presence of hbsag, hcv, or hiv antibodies. 17. patients at risk of needing cardiovascular surgical repair within the upcoming 12 months. 18. patient has unstable cardiovascular disease, such as advanced arteriosclerosis, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, cardiac conduction problems, exercise-related cardiac events including syncope and pre-syncope, risk factors for torsades de pointes (tdp) (e.g., heart failure, hypokalemia, family history of long qt syndrome), other serious or other clinically unstable cardiac problems as indicated by history, physical examination, or ecg. 19. any clinically significant condition or abnormal findings at the screening visit that would, in the opinion of the investigator, preclude study participation or interfere with the evaluation of the study medication. 20. any skin disease or condition that may affect treatment application, application site assessments, or absorption of the study drug. 21. history of treatment for, or evidence of, drug abuse within the past year. 22. patient responds "yes" to question '4' or '5' on the columbia suicide severity rating scale children (c-ssrs) during screening or at any time on study.

Keywords: 22qds chromosome 22q11.2 deletion syndrome autosomal dominant opitz g/bbb syndrome catch22 cayler cardiofacial syndrome conotruncal anomaly face syndrome (ctaf) shprintzen syndrome velo-cardio-facial syndrome (vcfs) velocardiofacial syndrome