A phase III study (physician-initiated clinical trial) to evaluate the efficacy and safety of sirolimus for epileptic seizures with focal cortical dysplasia type II

JRCT ID: jRCT2031230317

Registered date:04/09/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: focal cortical dysplasia type II
• Date of first enrollment: 07/09/2023
• Target sample size: 20
• Study type: Interventional
• Intervention(s): The study drug (sirolimus or placebo) will be administered orally once daily for 52 weeks. The investigational drug should be administered after meals or on an empty stomach (in principle, constant during the period of administration of the study drug).

Outcome(s)

• Primary Outcome: Relative reduction in the frequency of epileptic seizures from baseline (-4 to 0 weeks) for 21 to 24 weeks (times/28 days) after treatment

Secondary Outcome

(Double-blind period)
-Relative reduction in the number of epileptic seizures from baseline during each treatment period(excluding 21-24 weeks post-treatment)
-Relative reduction in the number of epileptic seizures from baseline from 1 to 24 weeks post-treatment
-Percent reduction from baseline in the number of epileptic seizures in each treatment period
-Response rate from baseline in the number of epileptic seizures in each treatment period
-Percentage of subjects lost without epileptic seizures in each treatment period
-Change from baseline in total duration of cluster seizures(including superimposed seizures)such as epileptic spasms and myoclonic seizures in each treatment period
-Percent relative decrease from baseline in the number of focal non-motor initiated seizures in each dosing period(continuous dosing period)

(Continuous administration period)
-Number of epileptic seizures in each treatment period compared to baseline
-Total duration of cluster seizures such as epileptic spasms and myoclonic seizures(including superimposed seizures)during each treatment period compared to baseline during each treatment period
-Number of focal non-motor onset seizures in each treatment period compared to baseline

Key inclusion & exclusion criteria

• Age minimum: >= 1age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

(1) Patients with a diagnosis of focal cortical dysplasia type II (including hemimegalencephaly) based on neuroimaging findings by head MRI within 156 weeks prior to enrollment or brain pathology prior to enrollment
(2) Patients aged 1 year or older at the time of consent
(3) Patients diagnosed with focal motor onset seizures (with motor signs which are able to be confirmed by others) or focal to bilateral tonic-clonic seizures associated with FCD based on the operational classification of seizure types by the International League Against Epilepsy (ILAE) 2017 (Appendix 1)
(4) Patients who have been treated with at least 2 antiepileptic drugs for at least 26 weeks since the diagnosis of epilepsy
(5) Patients on treatment with 1 to 4 antiepileptic drugs at the time of consent
(6) Patients whose dosage and administration of antiepileptic drugs has been constant for 8 weeks prior to enrollment
(7) Patients whose vagal nerve stiumulation therapy stimulation conditions have been constant for 8 weeks prior to enrollment
(8) Patients with at least 2 focal motor onset seizures (with motor signs which are able to be confirmed by others) or focal to bilateral tonic-clonic seizures during the 28-day baseline observation period
(9) Patients who provide written consent to participate in this study from the patient or a surrogate (parent or legal guardian).

Exclude criteria

(1)Patients who have participated in another clinical trial within 12 weeks prior to obtaining consent
(2)Patients who have taken sirolimus or everolimus within 52 weeks prior to enrollment
(3)Patients in whom neither the patient nor a surrogate can accurately record the number and duration of seizures
(4)Patients suspected of having progressive brain lesions on computed tomography(CT)or magnetic resonance imaging(MRI)performed to date
(5)Patients who have undergone neurosurgery for epilepsy(focal resection, cortical resection, functional hemispherectomy, corpus callosotomy, vagus nerve stimulation, or electrode implantation)within 26 weeks prior to enrollment
(6)Patients who are taking or have taken felbamate or vigabatrin within 26 weeks prior to enrollment
(7)Patients on a ketogenic diet
(8)Patients with previous suicide attempts
(9)Patients with a history or complications of substance abuse(including alcohol abuse)
(10)Patients of childbearing potential or male patients with a partner of childbearing potential who cannot agree to use contraception from the time of consent until 12 weeks after completion of study medication, patients who are pregnant or lactating, or patients who may be pregnant
(11)Patients with any of the following on clinical examination during the baseline observation period
-Patients whose AST or ALT levels are 2.5 times or more than the reference value
-Leukocytes count less than 3000 cells/mm3 or Ht less than 30%, platelets less than 80,000/mm3 or neutrophils less than 1000/mm3
-HBs antigen-positive patients, HBs antibody-positive or HBc antibody-positive patients except after hepatitis B vaccination, or patients with active hepatitis C(HCV antibody-positive patients are excluded if they are inactive and have normal liver function values)
-Patients with poorly controlled dyslipidemia, i.e., serum triglycerides >= 500 mg/dL or LDL cholesterol >= 190 mg/dL despite treatment for dyslipidemia
-Patients with abnormal renal function. That is, estimated glomerular filtration rate(eGFR)less than 30 mL/min/1.73 m2
(12)Patients with concomitant arrhythmias requiring treatment
(13)Patients with concomitant cardiac or renal insufficiency that may affect hemodynamics
(14)Patients with concomitant immunodeficiency
(15)Patients with fever over 38 degree celsius or active infection
(16)Patients with interstitial pneumonia at the time of enrollment
(17)Patients who have undergone surgery(surgery requiring intracorporeal invasion or more than 3 stitches, including biopsy)within 12 weeks prior to enrollment.
(18)Patients who are judged to be inappropriate for this study by the investigator(s).

Related Information

• Primary Sponsor: Kato Mituhiro