A single-arm open-label clinical trial on the efficacy and safety of sirolimus for epileptic seizures associated with focal cortical dysplasia type II: A study protocol

Epileptic seizures are core symptoms in focal cortical dysplasia (FCD), a disease that often develops in infancy. Such seizures are refractory to conventional antiepileptic drugs (AED) and temporarily disappear in response to AED in only 17% of patients. Currently, surgical resection is an important option for the treatment of epileptic seizures in FCD. In 2015, Korean and Japanese groups independently reported that FCD is caused by somatic mosaic mutation of the MTOR gene in the brain tissue. Based on these results we decided to test a novel treatment using sirolimus, an mTOR inhibitor, for epileptic seizures in patients with FCD type II. A single arm open-label clinical trial for FCD type II patients is being conducted in order to evaluate the efficacy and safety of sirolimus. The dose of sirolimus is fixed for the first 4 weeks and dose adjustment is achieved to maintain a blood level of 5 to 15 ng/mL during 8 to 24 weeks after initiation of administration, and it is kept within this level during a maintenance therapy period of 12 weeks. Primary endpoint is a reduction in the rate of incidence of focal seizures (including focal to bilateral tonic-clonic seizures) per 28 days during the maintenance therapy period from the observation period. To evaluate the frequency of epileptic seizures, registry data will be used as an external control group. We hope that the results of this trial will lead to future innovative treatments for FCD type II patients.