FIH Study of NRTX-1001 Neural Cell Therapy in Drug-Resistant Unilateral Mesial Temporal Lobe Epilepsy
- Conditions
- Mesial Temporal Lobe Epilepsy
- Interventions
- Biological: NRTX-1001Procedure: Sham Comparator
- Registration Number
- NCT05135091
- Lead Sponsor
- Neurona Therapeutics
- Brief Summary
This clinical trial is designed to test whether a single image-guided intracerebral administration of inhibitory nerve cells, called interneurons (NRTX-1001), into subjects with drug-resistant unilateral mesial temporal lobe epilepsy (MTLE), with or without mesial temporal sclerosis (MTS), is safe (frequency of adverse events) and effective (seizure frequency). NRTX-1001 comprises human interneurons that secrete a neurotransmitter, gamma-aminobutyric acid (GABA).
- Detailed Description
Subjects will undergo a single CT or MRI-guided intracerebral administration of human interneurons that secrete the inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), into the temporal lobe region of the brain where the seizures are thought to arise. NRTX-1001 is intended to suppress the onset and spread of seizures. Safety, tolerability, and effects on reducing seizure frequency and epilepsy disease symptoms will be assessed at quarterly intervals for 2 years after the administration of NRTX-1001. After the two-year period, subjects will be followed with quarterly phone calls and annual visits in years 3 through 5, and then annual visits in years 6 through 15. Subjects will be placed on an immunosuppressant medication regimen for a duration of one year to partially suppress the subjects' immune system to promote the intended long-term persistence of NRTX-1001. This immunosuppressant medication is intended to be discontinued after the first year; however, the NRTX-1001 cells are intended to persist long-term.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 58
- Male or Female, age ≥18 to 75
- Focal seizures, clinically defined as unilateral MTLE
- Has failed to achieve seizure control despite adequate trials of at least 2 ASDs at appropriate doses
- Currently on stable doses (at least 1 month) of approved ASDs
- Single seizure focus confirmed within one hippocampus
- Seizure frequency averages ≥4 per 28-day period, including at least 2 clinical focal seizures per 28-day period with objective manifestations or more severe types, over the 6 months prior to the Screening Visit.
- Considered (by Investigator) to be a candidate for temporal lobectomy (TL) or Laser Interstitial Thermal Therapy (LITT) following evaluation at a qualified epilepsy surgery program (National Association of Epilepsy Centers [NAEC] Level 4).
Key
- Epilepsy due to other and/or progressive neurologic disease
- Evidence of seizure focus outside of the hippocampus or evidence of seizures of non- focal origin.
- Significant other medical conditions which would impair safe participation
- History of status epilepticus in the year prior to screening. A history of cluster seizures is permitted.
- Primary or secondary immunodeficiency
- Suicide attempts in the past year
- Severe psychiatric disorders
- Prior lobectomy or LITT procedure
- MRI indicating potential malignant lesion
- Pregnancy, or currently breastfeeding.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description NRTX-1001 (Stage 2) NRTX-1001 Up to 20 subjects. Sham Comparator (Stage 2) Sham Comparator Up to 10 subjects. NRTX-1001 (Stage 1) NRTX-1001 Up to 10 subjects. NRTX-1001 (Phase 1) NRTX-1001 Up to 28 subjects NRTX-1001 (Phase 2) NRTX-1001 Up to 20 subjects Sham Comparator(Phase 2) Sham Comparator Up to 10 subjects.
- Primary Outcome Measures
Name Time Method Frequency of serious or severe AEs 1 year The primary endpoint of the study is the frequency of serious or severe AEs over the period of 1 year after administration, comparing all subjects treated with NRTX-1001 (Phase 1 + Phase 2) with all subjects who receive sham treatment.
- Secondary Outcome Measures
Name Time Method Change in seizure frequency 1 year The difference in the median percentage change from baseline in seizure frequency (seizures per 28 days) between subjects that receive NRTX-1001 and those who receive sham treatment, assessed in Phase 2.
Responder rate 1 year The difference in the 75% responder rate, e.g., the difference between the fraction of subjects who receive NRTX-1001 and those that receive sham treatment who experience at least a 75% reduction from baseline in seizure frequency, assessed in Phase 2.
Trial Locations
- Locations (29)
Mayo Clinic Arizona Epilepsy Center
🇺🇸Phoenix, Arizona, United States
Banner-University of Arizona Medical Center Tucson Comprehensive Epilepsy Program
🇺🇸Tucson, Arizona, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
University of Southern California Keck Hospital
🇺🇸Los Angeles, California, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
UC Irvine Medical Center
🇺🇸Orange, California, United States
Stanford University
🇺🇸Palo Alto, California, United States
University of California Davis
🇺🇸Sacramento, California, United States
University of California San Diego
🇺🇸San Diego, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
University of Colorado Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
University of Miami
🇺🇸Miami, Florida, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
University of Iowa Health Care
🇺🇸Iowa City, Iowa, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Wayne State University/Detroit Medical Center Comprehensive Epilepsy Program
🇺🇸Detroit, Michigan, United States
University of Nebraska
🇺🇸Omaha, Nebraska, United States
NYU Langone Comprehensive Epilepsy Center
🇺🇸New York, New York, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Atrium Health
🇺🇸Charlotte, North Carolina, United States
Duke University Hospital
🇺🇸Durham, North Carolina, United States
Atrium Wake Forest Baptist
🇺🇸Winston-Salem, North Carolina, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
UTHealth Houston
🇺🇸Houston, Texas, United States
University of Utah Health
🇺🇸Salt Lake City, Utah, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States