Clinical trial NCT05135091: FIH Study of NRTX-1001 Neural Cell Therapy in Drug-Resistant Unilateral Mesial Temporal Lobe Epilepsy
Official title: A First-In-Human (FIH) Study of Inhibitory Interneurons (NRTX- 1001) in Drug-Resistant Unilateral Mesial Temporal Lobe Epilepsy (MTLE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Mesial Temporal Lobe Epilepsy
Keywords: Epilepsy
MTLE
seizure
Lead sponsor: Neurona Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: California Institute for Regenerative Medicine (CIRM)
First posted: 2021-11-26
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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.

Eligibility criteria: Key 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).

Key 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.

Primary outcomes:
measure: Frequency of serious or severe AEs
timeFrame: 1 year
Secondary outcomes:
measure: Change in seizure frequency
timeFrame: 1 year
measure: Responder rate
timeFrame: 1 year
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona Epilepsy Center
state: Arizona
city: Tucson
country: United States
facility: Banner-University of Arizona Medical Center Tucson Comprehensive Epilepsy Program
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Los Angeles
country: United States
facility: University of Southern California Keck Hospital
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Health Care
state: Iowa
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University/Detroit Medical Center Comprehensive Epilepsy Program
state: Michigan
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: New York
country: United States
facility: NYU Langone Comprehensive Epilepsy Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Charlotte
country: United States
facility: Atrium Health
state: North Carolina
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Atrium Wake Forest Baptist
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Houston
country: United States
facility: UTHealth Houston
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health
state: Utah
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Neurona Therapeutics
name: John Hixson, MD
role: STUDY_DIRECTOR
References: