Clinical trial NCT04839601: RNS System RESPONSE Study
Official title: RNS® System Responsive Stimulation for Adolescents With Epilepsy Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Epilepsy
Partial Seizure
Neurostimulator; Complications
Drug Resistant Epilepsy
Focal Epilepsy
Keywords: Adolescent
Medically refractory
Responsive neurostimulation
Focal onset seizures
RNS System
Lead sponsor: NeuroPace
Sponsor class: INDUSTRY
First posted: 2021-04-09
Enrollment: 9
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To demonstrate that the RNS System is safe and effective as an adjunctive therapy in individuals age 12 through 17 years with medically refractory partial onset epilepsy.

Detailed description: NeuroPace is sponsoring the RESPONSE Study with the RNS System in individuals age 12 through 17 with partial (focal) onset seizures who have undergone diagnostic testing that localized no more than 2 epileptogenic foci, are refractory to two or more antiepileptic medications, and currently have frequent and disabling seizures. For the purposes of this study, disabling seizures are defined as motor partial seizures, complex partial seizures, and/or secondarily generalized seizures. The RNS System is currently approved by the FDA for use in patients 18 years and older with hard-to-treat partial-onset seizures. The same device will be used in the RESPONSE Study.

The study is a prospective open label single arm pivotal study and participants will be followed for 2 years after placement of the RNS System. The study will enroll a maximum of 200 subjects within the United States to ensure that at least 150 subjects are implanted with the RNS System.

The study design includes one interim analysis which will occur after the 75th implanted patient reaches 12 months post-implant. If the study achieves its primary safety and effectiveness endpoint goals at the interim analysis, the study will be considered successful and enrollment will be stopped.

If the interim analysis does not achieve the primary safety and effectiveness endpoint goals, the study will continue enrolling up to the maximum of 200 patients. A final analysis will be conducted after the 150th implanted patient reaches 12 months post-implant.

Eligibility criteria: Inclusion Criteria:

* Subject has disabling motor simple partial seizures, complex partial seizures, and/or secondarily generalized seizures. Disabling refers to seizures that are severe enough to cause injuries, or significantly impair functional ability in domains including employment, psychosocial education and mobility.
* Subject has seizures that are distinct, stereotypical events that can be reliably counted, in the opinion of the investigator, by the subject or parent/caregiver.
* Subject had an average of three or more disabling motor simple partial seizures, complex partial seizures and/or secondarily generalized seizures over the two most recent consecutive 30-day periods, with no 30-day period with less than two seizures per subject and/or parent/caregiver report.
* Subject failed treatment with a minimum of two anti-seizure medications (used in appropriate doses) with adequate monitoring of compliance and the effects of treatment, as determined by the investigator.
* Subject has undergone diagnostic testing as part of his/her standard care that has identified no more than two epileptogenic regions.
* Subject is male or a female of childbearing potential using a reliable method of contraception (hormonal, barrier method, surgical or abstention).
* Subject is age 12 or older but will be less than age 18 (has not reached 18th birthday) at the time of implantation with the RNS System.
* Subject is able to maintain an electronic diary alone or with the assistance of a competent individual.
* Subject is able to attend clinic appointments in accordance with the study schedule.
* Subject and/or parent/guardian must be willing and able to provide informed consent and assent when appropriate.
* Subject is not currently implanted with an RNS Neurostimulator or NeuroPace Leads.
* In the investigator's opinion, subject is able to tolerate a neurosurgical procedure.

Exclusion Criteria:

* Subject has been diagnosed with primarily generalized seizures.
* Subject requires procedures that are contraindicated based on current RNS System labeling.
* In the opinion of the investigator, the subject has a clinically significant or unstable medical condition (including alcohol and/or drug abuse) or a progressive central nervous system disease.
* Subject has been diagnosed with active psychosis, major depression or suicidal ideation in the preceding year. Subjects with post-ictal psychiatric symptoms need not be excluded.
* Subject is pregnant.
* Subject is participating in a therapeutic investigational drug or other device study.
* Subject is implanted with an electronic medical device that delivers electrical energy to the brain.
* Subject has been diagnosed with psychogenic or non-epileptic seizures.
* Subject has experienced unprovoked status epilepticus in the preceding year.
* Subject is taking chronic anticoagulants.

Note: For contraindications, refer to current physician labeling (manuals) for the RNS System available at the NeuroPace website (www.neuropace.com).

Primary outcomes:
measure: Short-term chronic serious adverse device effect (SADE) rate
timeFrame: 84-days post-implant
measure: Responder rate at 12 months post implant
timeFrame: The primary effectiveness endpoint is the percent of subjects with a ≥ 50% reduction in seizures at 12 months post-implant compared to the pre-implant baseline.
Secondary outcomes:
Other outcomes:
measure: Device-related Serious Adverse Event (SADE) event rate
timeFrame: Implant through 2 years post-implant
measure: Event rate of Serious Adverse Events (SAEs) of particular relevance
timeFrame: Implant through 2 years post-implant
measure: Affective status as measured by the Beck Depression Inventory
timeFrame: Implant through 2 years post-implant
measure: Neuropsychological functioning as assessed by a sub-set of tests in the NIH Toolbox Cognition Battery
timeFrame: Implant through 2 years post-implant
measure: Percentage change in seizure frequency
timeFrame: Implant through 2 years post-implant
measure: Quality of life as assessed by the Quality of Life in Epilepsy Inventory (QOLIE)
timeFrame: Implant through 2 years post-implant
Locations:
city: Grand Rapids
country: United States
facility: Spectrum Health System
state: Michigan
city: Hawthorne
country: United States
facility: Westchester Medical Center
state: New York
Study officials:
affiliation: NeuroPace, Inc.
name: Martha Morrell, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nair DR, Laxer KD, Weber PB, Murro AM, Park YD, Barkley GL, Smith BJ, Gwinn RP, Doherty MJ, Noe KH, Zimmerman RS, Bergey GK, Anderson WS, Heck C, Liu CY, Lee RW, Sadler T, Duckrow RB, Hirsch LJ, Wharen RE Jr, Tatum W, Srinivasan S, McKhann GM, Agostini MA, Alexopoulos AV, Jobst BC, Roberts DW, Salanova V, Witt TC, Cash SS, Cole AJ, Worrell GA, Lundstrom BN, Edwards JC, Halford JJ, Spencer DC, Ernst L, Skidmore CT, Sperling MR, Miller I, Geller EB, Berg MJ, Fessler AJ, Rutecki P, Goldman AM, Mizrahi EM, Gross RE, Shields DC, Schwartz TH, Labar DR, Fountain NB, Elias WJ, Olejniczak PW, Villemarette-Pittman NR, Eisenschenk S, Roper SN, Boggs JG, Courtney TA, Sun FT, Seale CG, Miller KL, Skarpaas TL, Morrell MJ; RNS System LTT Study. Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy. Neurology. 2020 Sep 1;95(9):e1244-e1256. doi: 10.1212/WNL.0000000000010154. Epub 2020 Jul 20.