Mesial Temporal Lobe Epilepsy
Conditions
Keywords
Epilepsy, MTLE, seizure, EPIC, focal seizures, hippocampus
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, efficacy, tolerability, and effects on reducing seizure frequency and epilepsy disease symptoms will be assessed at regular 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.
Interventions
BIOLOGICALNRTX-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.
PROCEDURESham Comparator
Sham Comparator
Sponsors
Neurona Therapeutics
California Institute for Regenerative Medicine (CIRM)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
This is a two-phase study. Phase 1/2 is open-label and unmasked. Phase 3 is blinded with participant, part of investigator team, and outcomes assessor masked to treatment assignment.
Intervention model description
This is a two-phase study. Phase 1/2 is an open-label, single arm, sequential dose escalation. Phase 3 is a multicenter, double-blind, randomized, parallel group, sham controlled study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion 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 prior to Screening) 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. (Phase 1/2 only) 7. Disabling seizure frequency of ≥2 per 28-day period averaged over 3 months prior to the Screening visit and over a prospective 10-week baseline period prior to Randomization (Phase 3 Only) Key
Exclusion criteria
1. Epilepsy due to other medical conditions 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 3 years prior to screening. 5. Primary or secondary immunodeficiency 6. Suicide attempts in the past year 3 years 7. Severe psychiatric disorders 8. Prior lobectomy or LITT procedure 9. MRI indicating potential malignant lesion 10. Pregnancy, or currently breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of serious or severe AEs (Phase 1/2) | 1 year | The primary endpoint of the study is the frequency of serious or severe AEs over the period of 1 year after administration. |
| Change in disabling seizure frequency (Phase 3) | 4-6 months after surgery | The difference in median percent change from baseline in diary-reported disabling seizure frequency (seizures per 28 days) between subjects that receive NRTX-1001 and those who receive sham treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Responder rate (Phase 3) | 4-6 months after surgery | The difference in the 50% 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 50% reduction from baseline in disabling seizure frequency. |
Countries
United States
Contacts
CONTACTNeurona MedInfo
CONTACTEduardo Dunayevich, MD
STUDY_DIRECTOREduardo Dunayevich, MD
Neurona Therapeutics
Outcome results
None listed