Sirolomus Adjuvant Treatment of Focal Refractory Epilepsy (SATFRE)

NCT06719791 | Recruiting Early Phase 1

• 1 other identifier: 2024-259-002
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to evaluate the clinical efficacy of sirolimus 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

Sirolomus; Focal Refractory Epilepsy; mTOR pathway

Outcome Measures

Primary Outcomes (2)

• Percent Change From Baseline in Seizure Frequency Per 28 Days

  Percent change in 28-day frequency of seizures during the 40 week treatment and follow-up period relative to baseline

  assessed per 28 days during the treatment.

• 50% Seizure Responder Rate

  The proportion of patients with a ≥ 50% reduction from Baseline in seizure frequency.

  short-term treatment period (ending at 3 months); long-term follow-up period (ending at 12 months).

Secondary Outcomes (3)

• Seizure Severity

  Baseline observation period; short-term treatment period (ending at 3 months); long-term follow-up period (ending at 12 months).

• Life quality evaluation

  Baseline observation period; short-term treatment period (ending at 3 months); long-term follow-up period (ending at 12 months).

• Adverse Events

  through study completion, 12 months.

Study Arms (1)

Open label single arm, drug sirolomus

EXPERIMENTAL

All subjects will receive the experimental drug

Drug: Sirolimus

Interventions

Sirolimus DRUG

Oral administration is given solely for the epilepsy seizure event. Dosage: The dosage is determined based on body surface area (BSA), with 0.5 mg per dose for BSA \<1.2 m², 1 mg per dose for BSA 1.3-2.1 m², and 1.5 mg per dose for BSA \>2.2 m².

Open label single arm, drug sirolomus

Eligibility Criteria

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

You may qualify if:

• years of age.
• Meet the 2017 International League Against Epilepsy (ILAE) diagnostic criteria for for focal seizures or focal seizures progressing to bilateral tonic-clonic seizures.
• Diagnosed with refractory epilepsy, having used at least two AEDs without effectiveness for 2 years. No drug interaction between current AEDs and sirolomus, and a stable dose for at least 12 weeks prior to enrollment.
• Seizure duration ≥1 minute, with accompanying sensory impairment.
• At least 6 focal seizures within the 12 weeks preceding enrollment.
• EEG or MRI/CT results within the past 2 years, confirming the diagnosis of focal epilepsy.
• The use of vagus nerve stimulation (VNS) and deep brain stimulation (DBS) is permitted, need to implant at least 5 months and stable for at least 12 weeks before enrollment.The parameters should keep unchanged until the end of the study.
• Informed consent signed.

You may not qualify if:

• Diagnosed with generalized or hereditary epilepsy with ion channel gene mutations
• Psychogenic non-epileptic seizures within 12 months;
• Treatable causes of epilepsy (such as metabolic disorders, toxicity, infections, space occupying lesions, or identified genetic abnormalities)
• Patients with only non-motor focal seizures, as classified by the 2017 ILAE.
• Seizure clusters within the 12 months.
• Tonic-clonic status epilepticus within12 months.
• Free of major medical illnesses including:
• Cerebrovascular events within the past 6 months, including cerebral infarction, cerebral hemorrhage, and transient ischemic attack, or those with progressive intracranial lesions.
• Severe uncontrolled diseases, such as immunodeficiency disorders, liver or kidney diseases, acute infections, or advanced-stage tumors.
• Severe cardiovascular or peripheral vascular diseases, such as those classified as NYHA Class III-IV, or those with malignant arrhythmias (e.g., Long QT syndrome, Brugada syndrome, and conduction block), or any other clinically significant electrocardiogram abnormalities, or who have had a myocardial infarction within the past 3 months before screening
• Participants with a history of medical conditions or surgeries that, in the investigator's judgment, could affect the absorption, distribution, or metabolism of the study drug (e.g., active peptic ulcers, ulcerative colitis, Crohn's disease, or bowel obstruction) or those with difficulty swallowing.
• Participants with any medical condition, mental health status, cognitive impairment, or intellectual disability that the investigator believes could increase the risk to the participant or interfere with their ability to participate in the clinical trial.
• Severe allergic reactions to any component of sirolimus, or have hypersensitivity.
• Participants meeting any of the following laboratory criteria: alanine aminotransferase (ALT) \>2× upper limit of normal (ULN), aspartate aminotransferase (AST) \>2× ULN, alkaline phosphatase (ALP) \>2× ULN, platelet count \<80×10\^9/L, neutrophil count \<1.8×10\^9/L, or creatinine clearance (CLcr) \<30 mL/min (calculated by the Cockcroft-Gault formula).
• In the period of pregnancy, childbirth, lactation.

Sponsors & Collaborators

• Xuanwu Hospital, Beijing: lead
• Peking University: collaborator

Study Sites (1)

Xuanwu Hospital

Beijing, China

RECRUITING

MeSH Terms

Conditions

Drug Resistant Epilepsy

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Liankun Ren, MD

  Xuanwu Hospital, Beijing

  PRINCIPAL INVESTIGATOR

• Zhuo Huang, PhD

  Peking University School of Pharmaceutical Sciences

  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: December 1, 2024
• First Posted: December 6, 2024
• Study Start: December 23, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: December 31, 2024

Record last verified: 2024-12

Locations

CN (1)