None listed
Conditions
Brief summary
A sequential, multi-stage, open-label, multi-national, multiple-center, multiple-dose study to assess the long-term safety and tolerability of ZYN002 (transdermal CBD gel) in child and adolescent epilepsy patients 3 to <18 years of age with seizures associated with developmental and epileptic encephalopathies (DEE) according to the International League Against Epilepsy (ILEA) classification. In Period A patients will undergo a baseline period of 4-weeks, followed by a 2-week titration period, and a 24-week maintenance period. Patients will be treated for a total of 26 weeks. For Patients not continuing to Period B, following Week 26 or Early Termination, study drug will be tapered over a 1 to 3-week period (depending on dose). After the final dose, patients will be followed weekly for 4 weeks by telephone. After the 4 weeks, the patient will be discharged from the study. Patients progressing to Period B will continue to receive ZYN002 for a further 24 weeks at the same maintenance dose received at Week 26 (e.g. end of Period A). Upon treatment termination, the patient will be required to complete the taper and follow-up period. After the final tapered dose, patients will be followed weekly for 4 weeks by telephone. After the 4 weeks of follow-up, the patient will be discharged from the study.
Interventions
A sequential, multi-stage, open-label, multi-national, multiple-center, multiple-dose study to assess the long-term safety and tolerability of ZYN002 in child and adolescent epilepsy patients 3 to <18 years of age having seizures associated with developmental and epileptic encephalopathies (DEE)
ZYN002 is a synthetically manufactured Cannabidiol (CBD), which is developed as a clear gel that can be applied to the skin (called transdermal delivery) to provide consistent, controlled levels of CBD i
A sequential, multi-stage, open-label, multi-national, multiple-center, multiple-dose study to assess the long-term safety and tolerability of ZYN002 in child and adolescent epilepsy patients 3 to <18 years of age having seizures associated with developmental and epileptic encephalopathies (DEE) ZYN002 is a synthetically manufactured Cannabidiol (CBD), which is developed as a clear gel that can be applied to the skin (called transdermal delivery) to provide consistent, controlled levels of CBD in the blood. The gel will be applied to clean, dry, intact skin of the upper arm from the top of the shoulder to the elbow, or upper thigh until area is dry. In Period A, all participants will undergo screening process. Eligible participants will then participate in a baseline period of 4 weeks. Subjects who meet baseline seizure requirements will initiate a 2-week titration period, followed by a 24-week maintenance period. Patients will be treated for a total of 26 weeks. For patients not progressing to Period B, following Week 26 or Early Termination, study drug will be tapered over a 1 to 3-week period depending on the patient’s dose at the time of taper). After the final dose, patients will be followed weekly for 4 weeks by telephone, prior to discharge from the study. Patients progressing to Period B will receive a further 24-weeks of open-label treatment. Upon treatment termination, there will be a taper period ranging from one to three weeks, depending on the patient’s dose at the time of the taper. Patients will complete an End of Study Visit (EOS) after completing their taper period. Patients who discontinue before Week 50 will be asked to attend the ET visit and then taper off the study medication. Patients weighing <25 kg will receive 125 mg CBD Q12H (+2 hours), for a total daily dose of 250 mg CBD (2 sachets) for the two-week titration period. Additional dose titration (up or down) during the maintenance period may be allowed based upon safety and efficacy parameters. Patients weighing >25 kg will receive 250 mg CBD Q12H (+2 hours), for a total daily dose of 500 mg CBD (4 sachets) for the two-week titration period. Additional dose titration (during the maintenance period) may be allowed based upon safety and efficacy parameters. At the end of the 26-week or 50-week treatment period, there will be a taper period ranging from one to three weeks, depending on a patient’s dose at the time of the taper. Patient compliance with the intervention will be monitored by the study coordinator through drug accountability at each study visit.
Sponsors
Zynerba Pharmaceuticals Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
3 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, 3 to less than 18 years of age, inclusive, at the time of screening. 2. Judged by the Investigator to be in generally good health at the Screening Visit based upon the results of a medical history, physical examination, 12-lead ECG, and clinical laboratory test results. 3. Patients must have a diagnosis of developmental and epileptic encephalopathy (DEE) as defined by the International League Against Epilepsy Classification (Scheffer 2017) with generalized motor, focal motor and focal impaired awareness or focal bilateral to tonic-clonic seizures. Examples of DEE that may be included, but not limited to: Lennox-Gastaut Syndrome, Dravet Syndrome, West Syndrome/ Infantile Spasms and Doose Syndrome. The diagnosis must be established for 1 years and documented by review of electroencephalogram (EEG), , and or genetic testing if available, and narrative from the physician who manages the patient’s epilepsy. The patient/legally authorized representation may elect to have the patient participate in genetic seizure panel testing to characterize a genetic diagnosis. 4. Patient must experience a threshold number of generalized motor seizures (i.e. tonic, clonic, atonic, tonic-clonic seizures, and generalized tonic-clonic), focal motor, focal impaired awareness or focal to bilateral tonic-clonic seizures during the Baseline period. 5. Patient is currently being treated and maintained with a stable regimen of between one (1) and four (4) AEDs for at least 4 weeks before screening, and willing to maintain a stable regimen during the treatment period. If a benzodiazepine is used as a rescue medication greater than 2 times per week, it will be counted as an AED. Patient taking ethosuximide, felbamate and vigabatrin must be on stable therapy for at least 6 months. Patient taking felbamate must have had no clinically relevant changes in hematology or liver function. 6. Patient has history of developmental delay with regression, slowing or plateau in at least one developmental domain. 7. All interventions for epilepsy must be stable for at least one month prior to screening. 8. Patient/caregiver is able and willing to maintain daily diaries for seizures, daily skin assessments and good day/bad day assessment. 9. Patient has a body mass index between 13 and 35 kg/m2 and weighs no less than 12 kg. 10. Sexually active females of childbearing potential must use an acceptable method of contraception. Acceptable methods of contraception include: hormonal contraception, diaphragm, cervical cap, vaginal sponge, condom, vasectomy, and intrauterine device. 11. Females of childbearing potential must have a negative pregnancy test at the Screening Visit, as well as at Day 1. 12. Patient is reasonably stable medically and is unlikely to require changes in drug therapy during the Treatment Period of the study, or interfere with the objectives of the study, or the ability to adhere to protocol requirements. 13. Patient/caregiver/legally authorized representative must be adequately informed of the nature and risks of the study and give written informed consent prior to screening. 14. In the Investigator’s opinion, the patient and/or caregiver is reliable and is willing and able to comply with all protocol requirements and procedures.
Exclusion criteria
1. Patient has a history of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to any adhesives, compound, or chemical class related to ZYN002 or its excipients. 2. Patient has been exposed to any investigational drug or device less than 30 days prior to screening or plans to take another investigational drug at any time during the study. 3. Patient has used cannabis or any CBD- or THC-containing product within 12 weeks of the Screening Visit or during the study. 4. Patient on the following AEDs for less than 6 months: ethosuximide, felbamate and vigabatrin. 5. Patient has had a change in AED regimen in the 4 weeks prior to screening. 6. Patient has alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels equal to 3x the upper limit of normal (ULN) as determined from Screening safety laboratories. 7. Patient/caregiver demonstrates behavior indicating unreliability or inability to comply with the requirements of the protocol. 8. Patient has had a change in epilepsy dietary therapy in the 4 weeks prior to screening. 9. Patient has seizures secondary to illicit drug or alcohol use. 10. Patient is using any strong inhibitor/inducer of CYP3A4 or sensitive substrate for CYP3A4 including the following medications: midazolam, oral ketoconazole, fluconazole, nefazodone, rifampin, alfentanil, alfuzosin, amiodarone, cyclosporine, dasatinib, docetaxel, eplerenone, ergotamine, everolimus, fentanyl, halofantrine, irinotecan, lapatinib, levomethadyl, lumefantrine, nilotinib, pimozide, quinidine, ranolazine, sirolimus, tacrolimus, temsirolimus, toremifene, tretinoin, vincristine, vinorelbine and St. John’s Wort. 11. Patient has a history of suicide attempt in the last 5 years or more than one lifetime suicide attempt. 12. Patient responds “yes” to Question 4 or 5 of C-SSRS (Children) during Screening and at any time during the study. 13. Patient has a positive result for the presence of Hepatitis B surface antigen (HBsAg), Hepatitis C virus antibodies (HCV-Ab), or human immunodeficiency virus (HIV) antibodies. 14. Patient has 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 treatment. 15. Patient has known history of cardiac disease. 16. Patient has any skin disease or condition, including eczema (on shoulders/arms, back or thighs), psoriasis, melanoma, acne (on shoulders/arms/back or thighs), contact dermatitis, scarring, imperfections, lesions, tattoos, or discoloration that may affect treatment application, application site assessments, or absorption of the study drug.
Outcome results
None listed