The phase 3 trial will include a double-blind period evaluating the safety and efficacy of cannabidiol (Epidiolex) for 14 weeks, followed by an open-label extension lasting 54 weeks.
Cannabidiol (CBD; Epidiolex), an FDA approved medication for rare epilepsies such as Dravet syndrome and tuberous sclerosis complex, will be evaluated in a phase 3 trial for children and adolescents with epilepsy with myoclonic-atonic seizures (EMAS), Jazz Pharmaceuticals announced.1
The pivotal study—GWEP20238 (NCT05288283)— is a 2-part, randomized, double-blind, placebo-controlled study that will enroll approximately 240 children and adolescents aged 1 to 18. Part A of the study will assess the efficacy and tolerability of CBD compared with placebo as an adjunctive treatment, while Part B will evaluate the long-term safety and tolerability of the medication.
"Given there are numerous treatment-resistant epilepsy syndromes, epileptologists often look for efficacy by seizure type, most of which have no syndrome-specific approved treatment. An EMAS indication would provide support for the use of Epidiolex in a fourth indication of a distinct, generalized seizure type, myoclonic-atonic seizures," Rob Iannone, MD, MSCE, executive vice president, global head, Research and Development, Jazz Pharmaceuticals, said in a statement.1 "Jazz is committed to continuing to generate clinical study data and real-world evidence to further support the utility of the Company's cannabidiol across a broad range of difficult-to-treat seizure types."
Part A is expected to comprise 26 weeks, including a 1- to 3-week screening period, 4-week baseline observation period, 14- week dose optimization treatment period, 10-day taper period, and a safety follow-up period. Upon completion of the double-blind phase (Part A), participants will have an option to continue in the 54-week open-label extension (Part B). CBD will be dosed at 2.5 mg/kg twice daily (BID); after 1 week, the dose will be increased to 5 mg/kg BID (10 mg/kg daily).
The trial was initiated based on preliminary data from the clinical development program, including real-world evidence that supported CBD as an effective therapy for EMAS. The primary outcome measures of the study include percent-change from baseline in EMAS-associated seizure frequency over the 14-week treatment period, and safety, as indicated by number of treatment-emergent adverse events (TEAEs). Secondary outcome measures included number of participants with at least 50% reduction in EMAS-associated seizures, total seizure frequency, and change in scores on Caregiver Global Impression of Change (CGIC) and Physician Global Impression of Change (PGIC), among others.
EMAS, typically known as Doose syndrome, is an uncommon childhood epilepsy syndrome that accounts for 1% to 2% of all childhood-onset epilepsies. More than two-thirds of children with EMAS will be boys, with the first seizure usually occurring between 2 and 6 years of age. Seizures in children with EMAS are often difficult to treat and may not respond well to medication. Medications are chosen based on seizure types: generalized tonic-clonic, myoclonic, and myoclonic atonic seizures are typically treated with valproic acid, lamotrigine, levetiracetam, topiramate, zonisamide, rufinamide, clobazam, and felbamate, while absence seizures are typically treated with ethosuximide, valproic acid, or lamotrigine.2
The CBD formulation, which Jazz acquired in early 2021 with its purchase of GW Pharmaceuticals, was originally approved by the FDA for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome in June 2018, and those associated with tuberous sclerosis complex in August 2020.3,4