The Safety and Efficacy Evaluation of Everolimus as an Adjunctive Treatment for Focal Refractory Epilepsy

NCT07095933 | Recruiting Early Phase 1 DMC

• 1 other identifier: 2025-218-002
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to evaluate the clinical efficacy of everolimus as an adjunctive therapy for refractory epilepsy. The significance lies in addressing whether the mTOR inhibitor sirolimus has antiepileptic adjunctive effects for a broader range of patients with refractory epilepsy, with the hope of providing a new mTOR-targeted antiepileptic adjunctive medication regimen that is administered only during epileptic events and can be widely used for various types of refractory epilepsy.

Conditions

Epilepsy; Drug Resistant

Keywords

Everolimus; Focal Refractory Epilepsy; Epilepsy memory; mTOR pathway

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Seizure Frequency Per 28 Days

  Percent change in 28-day frequency of seizures during the 12 week treatment and follow-up period relative to baseline

  assessed per 28 days during the treatment until the end of 12-week treatment.

Secondary Outcomes (4)

• 50% Seizure Responder Rate

  Baseline observation period, and 12-week treatment period (ending at 12 weeks).

• Seizure Severity

  Baseline observation period, and 12-week treatment period (ending at 12 weeks).

• Life quality evaluation

  Baseline observation period, and 12-week treatment period (ending at 12 weeks).

• Adverse Events

  through study completion, 12 weeks.

Study Arms (1)

Everolimus

EXPERIMENTAL

All subjects will receive the experimental drug.

Drug: Everolimus

Interventions

Everolimus DRUG

Oral administration is given solely for the epilepsy seizure event. Dosage: The dosage is determined based on body surface area (BSA), with 2.5 mg per dose for BSA \<1.2 m², 5 mg per dose for BSA 1.3-2.1 m², and 7.5 mg per dose for BSA \>2.2 m².

Everolimus

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age between 18 and 60 years (inclusive), regardless of sex.
• Diagnosis of epilepsy, meeting the criteria for focal seizures or focal to bilateral tonic-clonic seizures as defined by the 2017 International League Against Epilepsy (ILAE) classification.
• History of epileptic seizures lasting ≥30 seconds, accompanied by impaired awareness.
• At least 16 focal seizures during the 8-week baseline period prior to enrollment, with no seizure-free interval of 21 consecutive days.
• Diagnosis of drug-resistant epilepsy, defined as failure to achieve sustained seizure freedom despite adequate trials of at least two appropriately chosen and tolerated antiseizure medications (ASMs) over a period of 2 years. - Existing ASMs must have no known drug-drug interactions with everolimus and must have been administered at a stable dose for at least 12 weeks prior to enrollment.
• Use of vagus nerve stimulation (VNS) or deep brain stimulation (DBS) is permitted, provided the device was implanted at least 5 months prior to screening, with stimulation parameters stable for at least 12 weeks before enrollment and maintained unchanged throughout the study.
• Written informed consent to participate in the study, provided voluntarily by the subject.
• In the investigator's judgment, the subject is able to comply with the requirements of the study protocol, including understanding and completing seizure diaries, adhering to the visit schedule, and taking study medications as directed.

You may not qualify if:

• Diagnosis of primary generalized epilepsy.
• History of non-epileptic events (e.g., psychogenic non-epileptic seizures).
• Patients with only non-motor focal seizures according to the 2017 ILAE classification.
• Epilepsy with identifiable and treatable causes (e.g., metabolic disorders, intoxication, infection, space-occupying lesions, or confirmed genetic abnormalities).
• Inability to accurately count seizures due to excessively frequent episodes within the 12 months prior to study drug administration.
• History of epileptic seizure clusters within the 12 months prior to study drug administration.
• History of status epilepticus within the 12 months prior to study drug administration.
• Use of mTOR pathway inhibitors within the 12 months prior to study drug administration.
• History of cerebrovascular events (e.g., cerebral infarction, cerebral hemorrhage, or transient ischemic attack) or progressive intracranial lesions within the 6 months prior to study drug administration.
• Presence of severe uncontrolled diseases, including immunodeficiency disorders, hepatic or renal disease, acute infection, significant pulmonary dysfunction, or advanced malignancy.
• Severe cardiovascular or peripheral vascular disease, such as New York - Heart Association (NYHA) class III-IV heart failure, malignant arrhythmias (e.g., long QT syndrome, Brugada syndrome, conduction block), any other clinically significant ECG abnormalities, or myocardial infarction within 3 months prior to screening.
• History of any condition or surgery that, in the investigator's opinion, could affect absorption, distribution, or metabolism of the study drug (e.g., active gastric ulcer, ulcerative colitis, Crohn's disease, intestinal obstruction), or presence of dysphagia.
• Any medical condition, psychiatric disorder, cognitive impairment, or intellectual disability that, in the investigator's judgment, may increase the risk to the subject or interfere with study participation.
• Laboratory abnormalities meeting any of the following criteria: alanine aminotransferase (ALT) \>2× upper limit of normal (ULN), aspartate aminotransferase (AST) \>2× ULN, alkaline phosphatase (ALP) \>2× ULN, platelet count \<80×10⁹/L, neutrophil count \<1.8×10⁹/L, or creatinine clearance (CLcr) \<30 mL/min (calculated by the Cockcroft-Gault formula).
• Female subjects who test positive for pregnancy during screening or who are breastfeeding.

Sponsors & Collaborators

• Xuanwu Hospital, Beijing: lead

Study Sites (1)

Xuanwu Hospital, Beijing

Beijing, Beijing Municipality, 100053, China

RECRUITING

MeSH Terms

Conditions

Epilepsy

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Liankun Ren, MD

  Xuanwu Hospital, Beijing

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liankun Ren, MD

CONTACT

+86 13681576621; renlk2022@outlook.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 24, 2025
• First Posted: July 31, 2025
• Study Start: March 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)