FIH Study of NRTX-1001 Neural Cell Therapy in Drug-Resistant Unilateral Mesial Temporal Lobe Epilepsy

Purpose

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).

Condition

  • Mesial Temporal Lobe Epilepsy

Eligibility

Eligible Ages
Between 18 Years and 75 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Male or Female, age ≥18 to 75 2. Focal seizures, clinically defined as unilateral MTLE 3. Has failed to achieve seizure control despite adequate trials of at least 2 ASDs at appropriate doses 4. Currently on stable doses (at least 1 month) of approved ASDs 5. Single seizure focus confirmed within one hippocampus 6. 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. 7. 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).

Exclusion Criteria

  1. Epilepsy due to other and/or progressive neurologic disease 2. Evidence of seizure focus outside of the hippocampus or evidence of seizures of non- focal origin. 3. Significant other medical conditions which would impair safe participation 4. History of status epilepticus in the year prior to screening. A history of cluster seizures is permitted. 5. Primary or secondary immunodeficiency 6. Suicide attempts in the past year 7. Severe psychiatric disorders 8. Prior lobectomy or LITT procedure 9. MRI indicating potential malignant lesion 10. Pregnancy, or currently breastfeeding.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
This is a two-phase study. Phase 1 is an open-label, single arm, sequential dose escalation. Phase 2 is a parallel, randomized, 2-arm, sham controlled study.
Primary Purpose
Treatment
Masking
Triple (Participant, Investigator, Outcomes Assessor)
Masking Description
This is a two-phase study. Phase 1 is open-label and unmasked. Phase 2 is blinded with participant, part of investigator team, and outcomes assessor masked to treatment assignment.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
NRTX-1001 (Phase 1)
Up to 28 subjects
  • Biological: NRTX-1001
    Biological: NRTX-1001 is an experimental neural cell therapy product candidate derived from an allogeneic human embryonic stem cell line. The stem cells were converted into inhibitory nerve cells that produce GABA.
    Other names:
    • GABA-secreting interneurons
Experimental
NRTX-1001 (Phase 2)
Up to 20 subjects
  • Biological: NRTX-1001
    Biological: NRTX-1001 is an experimental neural cell therapy product candidate derived from an allogeneic human embryonic stem cell line. The stem cells were converted into inhibitory nerve cells that produce GABA.
    Other names:
    • GABA-secreting interneurons
Sham Comparator
Sham Comparator(Phase 2)
Up to 10 subjects.
  • Procedure: Sham Comparator
    Sham Comparator

Recruiting Locations

Mayo Clinic Arizona Epilepsy Center
Phoenix, Arizona 85054
Contact:
Kayla N Haeger, BSN, RN
480-342-5075
Haeger.Kayla@mayo.edu

Banner-University of Arizona Medical Center Tucson Comprehensive Epilepsy Program
Tucson, Arizona 85724-5023
Contact:
Faten Sebaali, BA/MA
520-626-3576
fsebaali@arizona.edu

University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205
Contact:
Shellah Rogers, Nurse
501-398-8622
Scrogers2@uams.edu

University of Southern California Keck Hospital
Los Angeles, California 90033
Contact:
Zoe B Durkin, SC
323-422-6625
zoe.durkin@med.usc.edu

University of California Los Angeles
Los Angeles, California 90095
Contact:
Suchi Tiwari, MBBS
310-825-4321
stiwari@mednet.ucla.edu

UC Irvine Medical Center
Orange, California 92868
Contact:
UCI Alpha Clinic
949-824-3990
alphaclinic@hs.uci.edu

Stanford University
Palo Alto, California 94304
Contact:
Jordan Seliger, CRC, MA
650-460-9260
jseliger@stanford.edu

University of California Davis
Sacramento, California 95817
Contact:
Evan Y Shen, BA
916-734-3009
evshen@ucdavis.edu

University of California San Diego
San Diego, California 92037
Contact:
Christian P Fulinara, BS
858-249-3038
chfulinara@health.ucsd.edu

University of California San Francisco
San Francisco, California 94143
Contact:
Vanessa R Anderson, BA
vanessa.anderson@ucsf.edu

University of Colorado Anschutz Medical Campus
Aurora, Colorado 80045
Contact:
Trey Jouard, MS
970-817-4272
Trey.Jouard@cuanschutz.edu

University of Miami
Miami, Florida 33136
Contact:
Letitia Fisher
305-243-3056
lfisher@miami.edu

Rush University Medical Center
Chicago, Illinois 60612
Contact:
Amanda Sremac, BS
312-942-0539
Amanda_C_Sremac@rush.edu

University of Chicago
Chicago, Illinois 60637
Contact:
Agnieszka Stadnik, MS
773-702-8996
astadnik@bsd.uchicago.edu

University of Iowa Health Care
Iowa City, Iowa 52242
Contact:
Loraine Brenner, MSN
319-356-4361
loraine-brenner@uiowa.edu

Ochsner Clinic Foundation
New Orleans, Louisiana 70121
Contact:
Neydin Osorio, BS, CRC
504-703-5577
neydin.tejeda@ochsner.org

Beth Israel Deaconess Medical Center
Boston, Massachusetts 02215
Contact:
Anna George, MSc
617-632-7031
ageorge5@bidmc.harvard.edu

Wayne State University/Detroit Medical Center Comprehensive Epilepsy Program
Detroit, Michigan 48201
Contact:
Kelly X Jia, MD
313-966-9407
xjia@med.wayne.edu

University of Nebraska
Omaha, Nebraska 68198
Contact:
Olga Taraschenko, MD, PhD
402-559-4086
olha.taraschenko@unmc.edu

NYU Langone Comprehensive Epilepsy Center
New York, New York 10016
Contact:
Jack C Carter, BS
646-558-0841
jack.carter@nyulangone.org

SUNY Upstate Medical University
Syracuse, New York 13210
Contact:
Lena F Deb, BA
315-464-9756
debl@upstate.edu

Atrium Health
Charlotte, North Carolina 28204
Contact:
Dianelis Diaz, RN, BSN, CRC
704-446-1900
dianelis.diaz@atriumhealth.org

Duke University Hospital
Durham, North Carolina 27710
Contact:
Hazani Benitez-Rosas
919-681-4974
Hazani.benitez-rosas@duke.edu

Atrium Wake Forest Baptist
Winston-Salem, North Carolina 27157
Contact:
Carolyn W Hedrick, RMA, CCRP
336-716-8694
cwhedric@wakehealth.edu

Oregon Health and Science University
Portland, Oregon 97239
Contact:
Claire Dorfman, BA
971-413-9201
dorfman@ohsu.edu

Thomas Jefferson University Hospital
Philadelphia, Pennsylvania 19107
Contact:
Latasha Adams, MBS
215-955-2606
Latasha.adams2@jefferson.edu

UTHealth Houston
Houston, Texas 77030
Contact:
Eliana M Klier, PhD
713-500-5442
Eliana.Klier@uth.tmc.edu

University of Utah Health
Salt Lake City, Utah 84108
Contact:
Laura Beeler, BS
801-585-9266
laura.beeler@hsc.utah.edu

Medical College of Wisconsin
Milwaukee, Wisconsin 53226
Contact:
Sarah Cornell, MS
414-955-0989
scornell@mcw.edu

More Details

NCT ID
NCT05135091
Status
Recruiting
Sponsor
Neurona Therapeutics

Study Contact

Sheri Madrid, BS, BA
949-500-0027
sheri@neuronatx.com

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.