Adjunctive Everolimus Treatment of Refractory Epilepsy

A Prospective, Randomized, Double-blind, Placebo-Controlled Phase Ⅱ Study to Evaluate the Efficacy of Adjunctive Everolimus Treatment in Patients With Refractory Epilepsy

This project is a prospective, randomized, placebo-controlled, double-blind study that will evaluate the clinical efficacy of everolimus as an adjunctive treatment in adult patients diagnosed with refractory epilepsy.

Study Overview

• Status: Recruiting
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Everolimus; Drug: Placebo

Detailed Description

The project consists of a screening and baseline monitoring period of 1-2 weeks, and a treatment period of 1 week, followed by a 3-month follow-up period. Approximately 108 participants will be randomized in a blinded manner to one of three arms in a 1:1:1 fashion (everolimus 1h : everolimus 8-9h : Placebo). After screening, participants will have the first video-EEG monitoring for up to 24 hours to assess baseline levels, followed by 1 week of treatment, the second video-EEG monitoring, and a 3-month post treatment follow-up period. During the treatment period, participants will be given everolimus or placebo directed to seizure events. In the "everolimus 1h" group, everolimus will be administrated immediately after seizure events (within 1 hour); while in the "everolimus 8-9h" group, everolimus administration will be delayed (at 8-9 hours after seizure events). We conduct this study to assess the efficacy of everolimus in adult refractory epilepsy patients under an administration strategy in a limited time window immediately after seizure events.

• Study Type: Interventional
• Enrollment (Anticipated): 108
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Weining Ma, MD.; Phone Number: 86-024-96615-36316; Email: maweining1985@163.com

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Recruiting
      • Shengjing hospital of China medical university
      • Contact: Weining Ma, MD.; Phone Number: 86-024-96615-36316; Email: maweining1985@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of drug resistant epilepsy, with treatment of at least two approved anti-epileptic drugs (AEDs), and having at least one reported seizure per month during the 3-month baseline phase and no continuous 3-month seizure-free period.
• Diagnosis of focal epilepsy without secondary generalization.
• Treatment with a stable dose of AEDs that must have no drug interactions with everolimus (eg, valproic acid, topiramate, oxazepine, phenobarbital, phenytoin, and primidone) for at least 12 weeks before enrollment.

Exclusion Criteria:

• History of non-drug treatment for epilepsy, eg, vagus nerve stimulation (VNS), ketogenic diet, and epilepsy surgery.
• Severe dysfunction in kidney.
• With significant infectious, immunologic, or oncologic comorbidity at the time of enrollment.
• Currently taking or previously treated systemically with an mammilian target of rapamycin (mTOR) inhibitor.
• History of seizures secondary to drug abuse, psychogenic nonepileptic seizures, or an episode of status epilepticus within 1 year before enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: everolimus 1h; The study participants will orally receive everolimus within 1 hour and placebo at 8-9 hours after each seizure event, but with intervals longer than 24 hours.	Drug: Everolimus; Everolimus will be administrated orally based on seizure events, with an administration interval longer than 24 hours. Participates with a body surface area (BSA) of <= 1.2 m^2, the dosage was 2.5 mg/time; for BSA 1.3-2.1 m^2, the dosage was 5 mg/time; and for BSA >=2.2 m^2, the dosage was 7.5 mg/time.; Other Names: Afinitor; Drug: Placebo; Vitamin C
Experimental: everolimus 8-9h; The study participants will orally receive placebo within 1 hour and everolimus at 8-9 hours after each seizure event, but with intervals longer than 24 hours.	Drug: Everolimus; Everolimus will be administrated orally based on seizure events, with an administration interval longer than 24 hours. Participates with a body surface area (BSA) of <= 1.2 m^2, the dosage was 2.5 mg/time; for BSA 1.3-2.1 m^2, the dosage was 5 mg/time; and for BSA >=2.2 m^2, the dosage was 7.5 mg/time.; Other Names: Afinitor; Drug: Placebo; Vitamin C
Placebo Comparator: placebo; The study participants will orally receive placebo both within 1 hour and at 8-9 hours after each seizure event, but with intervals longer than 24 hours.	Drug: Placebo; Vitamin C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline frequency of epileptic discharge	Comparing frequency of epileptic discharge during video-EEG monitoring after versus before treatment	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline seizure frequency	Comparing number of seizures in 3 months after treatment versus baseline	6 months
Change from baseline seizure types	Comparing types of seizures in 3 months after treatment versus baseline	6 months
Change from baseline frequency of seizure-free days	Comparing seizure-free days in 3 months after treatment versus baseline	6 months
Seizure-free rate	Patients remaining seizure free in 3 months after treatment	3 months
Change from baseline occurrence of secondary generalized seizure and status epilepticus	Comparing number of occurrence of secondary generalized seizure and status epilepticus in 3 months after treatment versus baseline	6 months
Quality of life questionnaire (QOLIE-31-Chinese version) scores	Comparing the scores at 3 months after treatment versus before treatment	3 months

Collaborators and Investigators

• Sponsor: National Institute on Drug Dependence, China
• Collaborators: Peking University; Shengjing Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2022
• Primary Completion (Anticipated): January 1, 2023
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: November 5, 2022
• First Submitted That Met QC Criteria: November 5, 2022
• First Posted (Actual): November 14, 2022

Study Record Updates

• Last Update Posted (Actual): November 14, 2022
• Last Update Submitted That Met QC Criteria: November 5, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: everolimus
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Drug Resistant Epilepsy; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: PKU-SJ-01-2021-V1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No