The SetPoint System as a Pro-Remyelination Therapy for Relapsing-Remitting Multiple Sclerosis: A Pilot Study

The MS pilot study will assess the safety and investigate the remyelinating effects of the SetPoint System (study device) in adult patients with patients diagnosed with relapsing-remitting multiple sclerosis (RRMS). The SetPoint System is intended for adjunctive use with standard of care therapy for RRMS. The study device contains a miniaturized stimulator (implant) that is surgically placed under general anesthesia on the vagus nerve through a small incision on the left side of the neck (implant procedure). The study will enroll up to 60 participants at up to 10 sites. All eligible participants will undergo the implant procedure. Half of the participants will receive active stimulation (treatment) and the other half will receive non-active stimulation (control). Following treatment evaluations at Week 24, there will be a one-way crossover of control subjects to active stimulation and a 72-week open-label follow-up with all subjects (treatment and control) receiving active stimulation to evaluate long-term safety.

TheMS pilot study is a 1:1 randomized, double-blind, sham-controlled, multicenter pivotal study enrolling up to 60 subjects at up to 10 study centers across the U.S. The study will assess the safety and investigate the remyelinating effects of the SetPoint System (study device) in adult patients with patients diagnosed with relapsing-remitting multiple sclerosis (RRMS). The SetPoint System is intended for adjunctive use with standard of care therapy for RRMS.. The study device contains a miniaturized stimulator (implant) that is surgically implanted inside the left side of the neck on the vagus nerve (implant procedure). The implant delivers a small amount of electricity (stimulation) to the nerve. All eligible subjects will undergo the surgery under general anesthesia. Half of the subjects will receive active stimulation (the treatment group) and the other half will receive non-active stimulation (the control group). Stimulation will be delivered for 1 min once per day for 24 weeks. Following treatment evaluations at Week 24, there will be a one-way crossover of control subjects to active stimulation and a 72-week open-label follow-up with all subjects (treatment and control) receiving active stimulation to evaluate long-term safety. Blinding will be maintained until the last enrolled and randomized subject completes Week 24 assessments, and the study database is locked.

Eligibility Criteria:
Inclusion Criteria:

* Age 22-55 years at informed consent.
* Diagnosis of RRMS by revised 2017 McDonald criteria.
* Latency delay \>118 milliseconds on baseline full-field transient pattern reversal visual evoked potential (VEP) in at least one eye. Both eyes can be included if they meet all inclusion criteria.
* Peri-papillary retinal nerve fiber layer (pRNFL) \> 70 microns on Optical Coherence Topography (OCT) in the VEP-qualifying eye (sufficient axons).
* Best corrected high-contrast visual acuity (HCVA) better than LogMAR 1.0 by ETDRS (20/200 Snellen equivalent or letter score of 35).
* Best corrected low-contrast letter acuity (LCLA) by Sloan chart (2.5% black on white) of no better than 40 letters in the VEP-qualifying eye (Snellen equivalent of 20/40). (Best corrected LCLA must be worse than best corrected HCVA.)
* Absence of clinical relapse and/or no sign of MRI activity (1 or more gadolinium enhancing lesions or new T2 lesion developments) for at least 12 months prior to study enrollment while on a stable regimen of high potency disease-modifying therapy (DMT) prior to informed consent: if low-potency DMT, the DMT must have been started and maintained for at least two years prior to consent. If high-potency DMT, DMT must have been started and maintained at least one year prior to consent.
* Score of 2.5 to 6.0 by Expanded Disability Status Scale (EDSS) at baseline, with at least of 2 on the functional systems pyramidal function.

Exclusion Criteria:

* Confounding ophthalmologic disease or impairments/conditions that could interfere with visual testing (e.g., cataracts, disc hemorrhage, macular star, cotton wool spots, macular degeneration, glaucoma, etc.).
* Concurrent neurological disorders, including known moderate or severe cervical myelopathy.
* Clinical optic neuritis within 6 months before screening.
* Documented optic neuritis in the qualifying eye greater than 5 years before screening.
* Change in DMT within 1 year (High-potency DMT) or 2 years (Low-potency DMT) before consent.
* Glucocorticoid use within 30 days before consent.
* Hypersensitivity/allergy to MRI contrast agents and/or unable to perform MRI (e.g., claustrophobia).
* Regular use of or dependency on nicotine products within the past year.
* Not a surgical candidate.