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

• ClinicalTrials.gov Identifier: NCT05135091
• Recruitment Status: Recruiting
• First Posted: November 26, 2021
• Last Update Posted: April 19, 2023
• Sponsor: Neurona Therapeutics
• Collaborator: California Institute for Regenerative Medicine (CIRM)
• Information provided by (Responsible Party): Neurona Therapeutics

Study Description

Brief Summary:

This clinical trial is designed to test whether a single stereotactic intracerebral administration of inhibitory nerve cells into subjects with drug-resistant mesial temporal lobe epilepsy is safe (frequency of adverse events) and effective (seizure frequency).

Condition or disease	Intervention/treatment	Phase
Mesial Temporal Lobe Epilepsy With Hippocampal Sclerosis	Biological: NRTX-1001; Procedure: Sham Comparator	Phase 1; Phase 2

Detailed Description:

Subjects will undergo a single stereotactic intracerebral administration of neural cells, called interneurons, that secrete the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).

Subjects will then take medicines to partially suppress their immune system (aimed to prevent the body from rejecting the cells) for 1 year. Safety, tolerability, evidence of neural cell viability and local inflammation (using MRI scans of the brain), and effects on epilepsy disease symptoms will be assessed for 2 years post-transplant. Subjects will be followed for an additional 13 years with quarterly phone contact and annual visits.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a two-stage study. Stage 1 is an open-label, single arm, sequential dose escalation. Stage 2 is a parallel, randomized, 2-arm, sham controlled study.
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: This is a two-stage study. Stage 1 is open-label and unmasked. Stage 2 is masked with participant, part of investigator team, and outcomes assessor masked to treatment assignment.
• Primary Purpose: Treatment
• Official Title: A First-In-Human (FIH) Study of Inhibitory Interneurons (NRTX- 1001) in Drug-Resistant Unilateral Mesial Temporal Lobe Epilepsy (MTLE)
• Actual Study Start Date: June 16, 2022
• Estimated Primary Completion Date: May 2025
• Estimated Study Completion Date: May 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: NRTX-1001 (Stage 1); Up to 10 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 Name: GABA-secreting interneurons
Experimental: NRTX-1001 (Stage 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 Name: GABA-secreting interneurons
Sham Comparator: Sham Comparator (Stage 2); Up to 10 subjects.	Procedure: Sham Comparator; Sham Comparator.

Outcome Measures

Primary Outcome Measures :

1. Frequency of serious or severe AEs [ Time Frame: 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 (Stage 1 + Stage 2) with all subjects who receive sham treatment.

Secondary Outcome Measures :

1. Change in seizure frequency [ Time Frame: 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 Stage 2.
2. Responder rate [ Time Frame: 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 Stage 2.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

1. Male or Female, age ≥18 to 55
2. Focal seizures, clinically defined as TLE
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 as within one temporal lobe
6. For subjects entering Stage 1, the seizure focus is either a) in the non-dominant hemisphere, or b) in the dominant hemisphere and the subject has a Rey Auditory Verbal Learning Test (RAVLT) assessed within one year of screening, or at the screening visit, that is at least 1.5 standard deviations below the population mean.
7. Seizure frequency averages ≥2 per 28-day period over the 6 months prior to screening.

Key Exclusion Criteria:

1. Epilepsy due to other and/or progressive neurologic disease
2. Significant other medical condition which would impair safe participation
3. Primary or secondary immunodeficiency
4. Suicide attempt in the past year
5. Severe psychiatric disorders
6. Chronic indwelling intracranial device
7. MRI indicating potential malignant lesion
8. Pregnancy, or currently breastfeeding

Contacts and Locations

Contacts

Contact: Sheri Madrid, BS, BA; 650-255-6885; sheri.madrid@neuronatx.com

Contact: C Priest, PhD; 650-392-0372; cpriest@neuronatx.com

Locations

United States, California

Stanford University; Recruiting

Palo Alto, California, United States, 94304

Contact: Jordan Seliger, CRC, MA 650-460-9260 jseliger@stanford.edu

Contact: Ruba Shaik, CRC, BS 650-546-1436 rubas@stanford.edu

Principal Investigator: Kevin Graber, MD

Sub-Investigator: Vivek Buch, MD

Sub-Investigator: Jaimie Henderson, MD

Sub-Investigator: Richard Lafayette, MD

Sub-Investigator: Jordan Seliger

University of California San Diego; Recruiting

San Diego, California, United States, 92037

Contact: Christian P Fulinara, BS 858-249-3038 chfulinara@health.ucsd.edu

Contact: Alpha Stem Cell Clinic 844-317-7836 alphastemcellclinic@ucsd.edu

Principal Investigator: Jerry J Shih, MD

United States, Colorado

University of Colorado Anschutz Medical Campus; Recruiting

Aurora, Colorado, United States, 80045

Contact: Trey Jouard, MS 970-817-4272 Trey.Jouard@cuanschutz.edu

Contact: Christopher Mizenko, MS 303-724-4117 Christopher.Mizenko@cuanschutz.edu

Principal Investigator: Lesley Kaye, MD

Sub-Investigator: Steven Ojemann, MD

Sub-Investigator: Daniel Kramer, MD

Sub-Investigator: Amanda Piquet, MD

Sub-Investigator: Naveed Chaudhry, MD

Sub-Investigator: Thomas Wodushek, PhD

Sub-Investigator: Christopher Mizenko

Sub-Investigator: Trey Jouard

Sub-Investigator: Michelle Sandoval

United States, Illinois

Rush University Medical Center; Recruiting

Chicago, Illinois, United States, 60612

Contact: Amanda Sremac, BS 312-942-0539 Amanda_C_Sremac@rush.edu

Contact: Rebecca McWilliams, BS 312-563-1025 Rebecca_McWilliams@rush.edu

Principal Investigator: Rebecca O'Dwyer, MD

Sub-Investigator: Travis Stoub, PhD

Sub-Investigator: Sepehr B Sani, MD

United States, New York

NYU Langone Comprehensive Epilepsy Center; Recruiting

New York, New York, United States, 10016

Contact: Latoya T King, MBS, MS, MPH 646-558-0838 Latoya.King@nyulangone.org

Contact: Irene Jun, BS 646-558-0818 Irene.Jun@nyulangone.org

Principal Investigator: Orrin Devinsky, MD

Sub-Investigator: Daniel Friedman, MD

Sub-Investigator: Werner Doyle, MD

Sub-Investigator: Thomas Wisniewski, MD

Sub-Investigator: Bruce Solitar, MD

SUNY Upstate Medical University; Recruiting

Syracuse, New York, United States, 13210

Contact: Lena F Deb, BA 315-464-9756 debl@upstate.edu

Contact: Marielle N De Masi, BS 315-464-9756 demasim@upstate.edu

Principal Investigator: Robert L Beach, MD, PhD

Sub-Investigator: Corey A McGraw, MD

Sub-Investigator: Harish Babu, MD, PhD

Sub-Investigator: Shahram Izadyar, MD

Sub-Investigator: Xiangping Zhou, MD, PhD

United States, North Carolina

Duke University Hospital; Recruiting

Durham, North Carolina, United States, 27710

Contact: Jodi Lennon, BSN, RN 919-613-9129 jodi.lennon@duke.edu

Contact: Beth Perry, RN, CCRP 919-681-2695 beth.perry@duke.edu

Principal Investigator: Derek Southwell, MD, PhD

Sub-Investigator: Joanne Kurtzberg, MD

Sub-Investigator: Austin Dixon, MD, MBA

Sub-Investigator: Sidney Gospe III, MD, PhD

Sub-Investigator: Jill Stuart, PhD

Sub-Investigator: Mitchell E Horwitz, MD

Sub-Investigator: Beth Shaz, MD, MBA

Sub-Investigator: Matthew Luedke, MD

United States, Oregon

Oregon Health and Science University; Recruiting

Portland, Oregon, United States, 97239

Contact: Monica Dolan, R.N. 503-494-7224 dolan@ohsu.edu

Contact: Megan Pattle, R.N. 503-494-7191 rossme@ohsu.com

Principal Investigator: David C Spencer, MD

Sub-Investigator: Kim Burchiel, MD

Sub-Investigator: Paul Motika, MD

Sub-Investigator: Lia Ernst, MD

Sub-Investigator: David Pettersson, MD

Sub-Investigator: Michael Lane, MD

Sub-Investigator: Tyler Duffield, PhD

United States, Pennsylvania

Thomas Jefferson University Hospital; Recruiting

Philadelphia, Pennsylvania, United States, 19107

Contact: Mary E Sweeney, BA 215-955-2524 Mary.Sweeney2@jefferson.edu

Contact: Emily Patunas, CRC 215-955-8648 Emily.Patunas@jefferson.edu

Principal Investigator: Michael Sperling, MD

United States, Utah

University of Utah Health; Recruiting

Salt Lake City, Utah, United States, 84108

Contact: Laura Beeler, BS 801-585-9266 laura.beeler@hsc.utah.edu

Contact: Marissa Castillo, BS 801-585-9266 marissa.castillo@hsc.utah.edu

Principal Investigator: Amir Arain, MD

Sub-Investigator: Sindhu Richard, MD

Sub-Investigator: Brian Johnson, MD

Sub-Investigator: Blake Newman, MD

Sub-Investigator: Angela Peters, MD

Sub-Investigator: Katherine Krulisky, MD

Sub-Investigator: Shervin Rahimpour, MD

Sub-Investigator: Michelle Miranda, PhD, MPH

Sub-Investigator: Jonathan Galli, MD

United States, Wisconsin

Medical College of Wisconsin; Recruiting

Milwaukee, Wisconsin, United States, 53226

Contact: Sarah Cornell, MS 414-955-0989 scornell@mcw.edu

Contact: Kaitlin Goetschel, BS 414-955-7398 kgoetschel@mcw.edu

Principal Investigator: Sean Lew, MD

Sponsors and Collaborators

Neurona Therapeutics

California Institute for Regenerative Medicine (CIRM)

Investigators

• Study Director: David Blum, MD; Neurona Therapeutics

More Information

• Responsible Party: Neurona Therapeutics
• ClinicalTrials.gov Identifier: NCT05135091
• Other Study ID Numbers: NTE001
• First Posted: November 26, 2021
• Last Update Posted: April 19, 2023
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Epilepsy; Epilepsy, Temporal Lobe; Hippocampal Sclerosis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsies, Partial; Epileptic Syndromes; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Congenital Abnormalities