Trial Investigating the Safety and Efficacy of BRC-003 in Refractory Post-Traumatic Epilepsy (PTE)

A Randomized Controlled Trial Investigating the Safety and Efficacy of BRC-003 in Refractory Post-Traumatic Epilepsy

This prospective double blind phase II study seeks to evaluate the safety and efficacy of BRC-003, a high CBD investigational product, in the treatment of refractory PTE (Post-Traumatic Epilepsy). The research is divided into two phases: an open-label dose-finding phase (Part A) and a subsequent randomized controlled phase (Part B). This design aims to provide a thorough understanding of the investigational product's impact on seizure frequency, seizure severity, mood, anxiety, sleep, and quality of life.

Study Overview

• Status: Withdrawn
• Conditions: Post-traumatic Epilepsy
• Intervention / Treatment: Drug: Placebo; Drug: PO BRC-003 (High Cannabidiol Cannabis Extract)

Detailed Description

Post-traumatic epilepsy (PTE) is a debilitating disorder characterized by recurrent seizures that develop following traumatic brain injury (TBI). Approximately 30 to 50% of patients with PTE may develop refractory epilepsy, wherein seizures persist despite treatment with multiple antiseizure medications (ASMs) or other therapeutic intervention. Moreover, the debilitating side effects of some ASMs can impact treatment compliance and patient quality of life; the side effects of ASMs may be more severe in patients with PTE.

Cannabis sativa L. has an extensive history of medical and therapeutic use. Growing interest in the utility of cannabinoids for medical indications including epilepsy, pain, nausea, appetite stimulation, muscle spasticity, and psychological disorders has led to its legalization in at least 14 countries as well as the regulatory approval of cannabis extract preparations, synthetic cannabinoids, and analogues. Cannabidiol (CBD), a non-intoxicating cannabinoid, has shown significant anticonvulsant properties and has received FDA (Food and Drug Administration) approval in three refractory seizure disorders.

This prospective study seeks to evaluate the safety and efficacy of BRC-003, a high CBD investigational product, in the treatment of refractory PTE. The research is divided into two phases: an open-label dose-finding phase (Part A) and a subsequent randomized controlled phase (Part B). This design aims to provide a thorough understanding of the investigational product's impact on seizure frequency, seizure severity, mood, anxiety, sleep, and quality of life.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Winchester, Virginia, United States, 22601
      • Winchester Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants must meet all of the following criteria to be eligible for enrollment into the study:

1. Diagnosis consistent with PTE,

   - and -

2. History of a trial of at least two AEDs, including one trial of a combination of two concomitant AEDs, without successful seizure control. Vagus nerve stimulation (VNS), RNS, deep brain stimulation (DBS), or the ketogenic diet can be considered an equivalent to a drug trial,
3. Between 1-4 baseline anti-epileptic drugs at stable doses for a minimum of 4 weeks prior to enrollment,
4. VNS, DBS, or RNS must be on stable settings for a minimum of 3 months,
5. If on ketogenic diet, must be on stable ratio for a minimum of 3 months.
6. If applicable, documentation (including date of surgery) of prior VNS, DBS, RNS, Corpus Callosotomy, or other epilepsy surgery the patient has received.
7. Age 18 years and older
8. Acceptable method of contraception (or abstinence) for women of childbearing potential and for male patients with partners of childbearing potential; female patients must have a negative urine pregnancy test on the day of initiating IMP.
9. Weight ≥ 40 kg

Exclusion Criteria:

• Participants meeting any of the following criteria will not be eligible for participation in the study:

  1. Active psychogenic non-epileptic seizures (PNES),
  2. Patients who are pregnant, breastfeeding, or not using acceptable methods of contraception during the course of the study and for three months thereafter,
  3. Male patient's partner is of childbearing potential; unless willing to ensure that they (male patients) or their partner(s) are using acceptable methods of contraception during the course of the study and for three months thereafter,
  4. Use of medical marijuana, cannabis, hemp, or CBD based product in the previous 30 days, or during the study.
  5. Weight ≤ 40 kg
  6. Initiation of felbamate within the last 12 months,
  7. Allergy to CBD or any cannabis-type products,
  8. ALT >5 × ULN or AST >5 × ULN, as seen in participant's laboratory results,
  9. Hemoglobin <10 or hematocrit <30 or WBC < 2000, as seen in participant's laboratory results,
  10. Current (as assessed via C-SSRS) or history of suicidal ideation or attempt,
  11. In PI's judgment, active medical condition/treatment that impacts study activities,
  12. Unable to provide consent,
  13. No access to a mobile phone, and internet, not willing or able to download the eDiary application,
  14. Inability or failure to comply with study visits, requirements and/or instructions, and
  15. For Part B, prior enrollment in Part A of the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A and Part B; Interventions: Drug: BRC-003 (High Cannabidiol Botanical Extract) 100 mg/mL	Drug: PO BRC-003 (High Cannabidiol Cannabis Extract); The research is divided into two phases: an open-label dose-finding phase (Part A) and a subsequent randomized controlled phase (Part B).; Other Names: CBD, Cannabis Extract, Cannabinoids
Placebo Comparator: Part B; Placebo Comparator: 1 Placebo Half of the patients will receive PO placebo Interventions: Drug: Placebo	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety assessment	Adverse events (AEs) and serious AEs (SAEs). The incidence of adverse events as measure of subject safety [Time Frame: Day 0 - Day 84] The number of subjects who experienced an adverse event during the study.; Vital signs; Laboratory assessments	Day 84
Efficacy assessment	Change from baseline to 12 weeks (post-treatment) in number of Post-Traumatic Epilepsy (PTE) -associated seizures	Day 84

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients considered treatment responders defined as those with a ≥ 50% reduction in PTE-associated seizure frequency.	Measured by the number of patients considered treatment responders	Day 84
Number of patients considered treatment responders defined as those with a ≥ 25%, ≥ 50%, ≥ 75% or 100% reduction in PTE-associated seizure frequency.	Measured by the number of patients considered treatment responders	Day 84
Number of patients experiencing a > 25% worsening, - 25 to + 25% no change, 25-50% improvement, 50-75% improvement or > 75% improvement in PTE-associated seizure frequency	Measured by the number of patients considered treatment responders	Day 84
Change in number of PTE-associated seizure-free days.	per medical chart review	Day 84
Seizure severity	via the Seizure Severity Questionnaire (SSQ). Minimum value: 11, Maximum value: 77. The lower the score, the better the outcome.	Day 84
Emotional distress/depression Information System (PROMIS) Short Form	via the Patient-Reported Outcomes Measurement. Minimum score: 4, Maximum score: 20. The lower the score, the better the outcome.	Day 84
Sleep disturbance	via the PROMIS Short Form. Minimum score: 4, Maximum score: 20. The lower the score, the better the outcome.	Day 84
Performance of Social Roles and Activities	via the PROMIS Short Form. Minimum score: 4, Maximum score: 20. The lower the score, the better the outcome.	Day 84
Anxiety	via the General Anxiety Disorder-7 (GAD-7) scale. 0-4: minimal anxiety, 5-9: mild anxiety, 10-14: moderate anxiety, 15-21: severe anxiety	Day 84
Quality of life measurement	via QOLIE-31. Contains 17 multi-item measures of overall quality of life, emotional well-being, role limitations due to emotional problems, social support, social isolation, energy/fatigue, worry about seizure, medication effects, health discouragement, work/driving/social function, attention/concentration, language, memory, physical function, pain, role limitations due to physical problems, and health perceptions.	Day 84
Use and effectiveness and of concomitant and frequency of rescue medications.	per medical chart review	Day 84

Collaborators and Investigators

• Sponsor: Dr. Paul Lyons
• Collaborators: Biopharmaceutical Research Company
• Investigators: Principal Investigator: Paul D Lyons, MD. PhD, Valley Health System

Publications and helpful links

General Publications

• (Irimia & Van Horn, 2015; Wang et al., 2017)
• (Ding et al., 2016).

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2024
• Primary Completion (Actual): April 15, 2025
• Study Completion (Actual): April 15, 2025

Study Registration Dates

• First Submitted: July 15, 2024
• First Submitted That Met QC Criteria: July 22, 2024
• First Posted (Actual): July 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2025
• Last Update Submitted That Met QC Criteria: April 18, 2025
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Epilepsy; Epilepsy, Post-Traumatic; Anticonvulsants; Cannabidiol
• Other Study ID Numbers: VHS-LY01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes