A PIVOTAL STUDY EVALUATING SAFETY AND EFFICACY OF THE SHIRATRONICS MIGRAINE THERAPY SYSTEM

Prior treatment

• History of treatments that could confound the results of the study
  • Previously implanted neurostimulator to stimulate the greater occipital and/or supraorbital nerves to treat headache.
  • Have received onabotulinumtoxinA (Botox) for any other medical or cosmetic reasons requiring injections in the head, face, or neck within 3 months prior to screening.
• Subjects with recent brain or facial trauma occurring less than 3 months prior to the Baseline Visit.
• Subjects that may have received sequential multi-day in-patient parenteral infusion for the treatment of a migraine condition (e.g., status migrainosus) within the previous 2 weeks of the initiation of diary screening phase.
• Subjects with any metallic implant located in the head including CSF shunt and surgical clip above the shoulder line (excluding dental implants).
• Use of nerve blocks, acupuncture, neurostimulation and/or transcranial magnetic stimulation) for migraine within 3 months prior to screening and after receiving implant system.
• Any pre-existing or requirement of emergent surgery/procedure that may interfere or confound the results of the study.
• Any known requirement for an MRI scan subsequent to implant of the neurostimulator.
• Currently participating in or planning to participate in other investigational drug or device studies that may interfere or confound the results of the study.

Other illness

• Subject has other implanted electrical stimulation device(s) including:
  • Cardiac pacemakers or defibrillators
  • Cochlear implant
  • Intrathecal pumps
  • Spinal cord stimulator
  • Other stimulator device
• Current or history of following comorbidities:
  • Clinically significant psychiatric illnesses, including suicide attempt, or suicidal ideation with a specific plan in the past 2 years.
  • Cancer in the past 5 years, except for appropriately treated nonmelanoma skin carcinoma.
  • Have a current diagnosis or condition that presents excess risk for performing the procedure, as determined clinically by the Investigator.
  • Substance use disorder of at least moderate severe for substances such as; alcohol, recreational marijuana, or illicit drugs during the past 2 years.

Other

• Type of headache or migraine other than RCM including the following:
  • Post-traumatic headache (e.g., battlefield, accidents, etc.).
  • Regular intake of opioids (including codeine) of ≥ 8 days in the past 3 months and during the 28-day screening/baseline phase and cannot be accounted for by another diagnosis.
  • Regular intake of Barbiturates for ≥ 5 days/month in the past 3 months and during the 28-day screening/baseline phase and cannot be accounted for by another diagnosis.
  • Report experiencing unremitting, continuous headaches with no relief.
  • Have new daily persistent headache (NDPH) defined by iCHD-3 as persistent headache, daily from its onset, which is clearly remembered. The pain lacks characteristic features and may be migraine-like or tension-type like or have elements of both with a CM subtype.
• Have had any cervical radiofrequency ablation within 12 months.
• Unable to participate or successfully complete the study, in the opinion of the investigator.
• Anatomy not suitable for placement of the study device.
• Are currently a study center or Sponsor employee who is directly involved in the study or the relative of such an employee.
• Pregnant or lactating female or planning a pregnancy during participation in the study.
• Patient with life expectancy of less than 1.5 years.

• ≥ 22 years of age.
• Have migraine onset at ≤ 50 years of age.
• Have a history of migraine for ≥ 12 months prior to screening.
• Have 15 - 26 headache days/month, among which ≥ 8 days has the features of probable migraine, and minimum of 2 headache-free days/month during the 28-day screening period.
• Fulfill the criteria for chronic migraine (CM) during the 28-day screening period.
• Have a diagnosis of refractory chronic migraine (RCM), who have inadequate response or no access to, or are intolerant, unwilling, or contraindicated to Onabotulinum toxin A (Botox) therapy, and One of the medications that belong to Calcitonin Gene Related Peptide Monoclonal antibodies (CGRP) therapy or CGRP antagonist therapy.
• Maintain a stable use of preventive(s) migraine medication for ≥ 3 months before screening. Subjects receiving OnabotunlinumtoxinA must stop therapy ≥ 3 months prior to screening visit.
• Demonstrate ≥ 80% compliance with the headache diary during the screening period by entering headache data on a minimum of 22 out of 28 days.
• Be willing and able to comply with all study procedures and return to the clinic for the follow-up evaluation, as specified in this protocol.
• Be able to give voluntary, written informed consent to participate in this study.