(223 days)
The Magnus Neuromodulation System with SAINT Technology is indicated for the treatment of Maior Depressive Disorder (MDD) in adult patients who have failed to achieve satisfactory improvement from prior antidenressant medication in the current episode.
The Magnus Neuromodulation System (MNS) with SAINT Technology is a non-invasive repetitive transcranial magnetic stimulation (rTMS) system that delivers individualized and navigationally directed repetitive magnetic pulses to the left dorsolateral prefrontal cortex (L-DLPFC) to treat Major Depressive Disorder (MDD) in adult patients who have failed to achieve satisfactory improvement from prior antidepressant medication in the current episode.
The MNS with SAINT Technology is available for prescription use only and is intended for use by trained medical professionals in either an inpatient or outpatient setting.
The Magnus Neuromodulation System consists of hardware devices (stimulator with treatment coil and neuronavigation system) intended to deliver SAINT Technology; that is, rTMS (as intermittent theta burst stimulation (iTBS)) to a target area within the L-DLPFC along with proprietary software informed by structural and functional MRI and designed to identify the individualized target within the L-DLPFC for stimulation. Also included in the system are a coil and monitor for motor threshold determination, which is used to inform patient-specific stimulation settings. SAINT Technology is the combination of using the specific individualized target for treatment along with a proprietary accelerated treatment protocol that condenses treatment to five days. The Magnus Neuromodulation System is designed to support successful delivery of SAINT Technology.
Here's a breakdown of the acceptance criteria and the study details for the Magnus Neuromodulation System (MNS) with SAINT Technology, based on the provided FDA 510(k) summary:
The document does not explicitly state "acceptance criteria" in a quantitative table for this device as it would for a diagnostic AI. Instead, the submission argues for substantial equivalence to a predicate device (Nexstim NBT System 2) by demonstrating comparable safety and effectiveness, meaning the "acceptance criteria" were met by showing performance akin to or exceeding the predicate, without introducing new safety concerns. The performance is primarily evaluated by achieving a high rate of response and remission in Major Depressive Disorder (MDD).
1. Table of Acceptance Criteria (Implied) and Reported Device Performance
| Parameter | Implied Acceptance Criteria (via Predicate Equivalence) | Reported Device Performance (SAINT Technology) |
|---|---|---|
| Effectiveness (Response Rate) | Comparable to predicate (THREE-D iTBS: 49% HDRS reduction ≥50%) | Study #1 (Open-label): 83.3% (MADRS reduction ≥50%) Study #2 (Open-label): 90.5% (MADRS reduction ≥50%), 86.4% (HDRS-17 reduction ≥50%) Study #3 (Active arm, RCT): 85.7% (MADRS reduction ≥50%) Study #4 (Open-label): 92.8% (MADRS reduction ≥50%) |
| Effectiveness (Remission Rate) | Comparable to predicate (THREE-D iTBS: 32% HDRS-17 ≤7) | Study #1 (Open-label): 83.3% (MADRS ≤10) Study #2 (Open-label): 90.5% (MADRS ≤10), 77.3% (HDRS-17 ≤7) Study #3 (Active arm, RCT): 78.6% (MADRS ≤10) Study #4 (Open-label): 78.6% (MADRS ≤10) |
| Safety | No new or increased safety concerns compared to predicate | Zero serious adverse events (SAEs) reported across all four SAINT studies. Non-serious adverse events are similar in type and incidence to the predicate device (THREE-D iTBS), with the exception of increased fatigue (likely due to extended daily treatment time for SAINT) and potentially some back/neck pain due to time spent in clinic. |
| Target Identification | Aid in localization of appropriate target areas within the L-DLPFC for stimulation | Proprietary software utilizing structural and functional MRI data to locate the target area within the L-DLPFC for depression therapy. Provides more individual specificity than historically used external anatomical landmarks. |
| Stimulation Protocol | Delivery of iTBS, comparable efficacy to predicate | Optimized and compressed iTBS treatment schedule over 5 days (90,000 pulses total, 10 sessions/day) compared to predicate (18,000 pulses total, 1 session/day over 6 weeks). Magnetic field intensity at 90% Motor Threshold for SAINT vs. 120% Motor Threshold for predicate, which "may be safer and more focal, and may be more effective." |
Study Proving Acceptance Criteria (Clinical Studies of SAINT Technology)
The device's performance is demonstrated through four clinical studies using SAINT Technology, which are summarized and compared to the predicate device in the provided document.
2. Sample Sizes Used for the Test Set and Data Provenance
The "test set" in this context refers to the participant groups in the clinical trials that evaluated the SAINT Technology.
- Study #1: 6 participants.
- Study #2: 21 participants (22 recruited, 1 ineligible, 1 withdrew on Day 1).
- Study #3 (Randomized Controlled Trial): 29 participants (14 active, 15 sham).
- Study #4 (Open-label Pilot): 14 participants.
Total Participants across all SAINT studies: 70 patients.
Data Provenance: The document states that these studies were "conducted in close geographical proximity." While a specific country is not explicitly named, the context of FDA submission and US-based company suggests these were likely US-based studies. All studies appear to be prospective clinical trials, tracking patients through treatment and follow-up. The note explicitly states: "As a result of studies being performed at a single site, generalizability to the broader United States population has not been evaluated."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The concept of "ground truth" for a diagnostic AI (e.g., expert reads of images) doesn't directly apply here in the same way, as this device is a neuromodulation therapy for MDD, not a diagnostic tool requiring expert interpretation for diagnosis. The "truth" for its effectiveness is based on patient-reported outcomes and clinician-rated scales (MADRS, HDRS), which are standard, validated instruments in psychiatry. The administration and interpretation of these scales would typically be performed by trained clinical staff and psychiatrists involved in the studies, who serve as the evaluators of patient response to treatment. Specific numbers or qualifications of individual "experts" for this "ground truth" (i.e., MADRS/HDRS scoring) are not provided, as it's an inherent part of clinical trial methodology.
4. Adjudication Method for the Test Set
Adjudication methods (like 2+1, 3+1 for discrepancies) are typically used for establishing ground truth in diagnostic studies where multiple readers might interpret data. Since this is a treatment device whose efficacy is measured by standardized psychiatric scales, such an "adjudication method" for the test set is not explicitly described in the context of expert consensus on a diagnosis or finding. The clinicians administering rating scales would be trained and standardized to minimize inter-rater variability as part of good clinical practice. In Study #3, it was a randomized, blinded trial where response and remission were assessed by clinicians blind to treatment allocation.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done in the typical sense this term is used for AI-assisted diagnostic devices (i.e., comparing multiple human readers' diagnostic accuracy with and without AI assistance).
The studies described evaluate the effectiveness of the device (SAINT Technology) as a treatment for MDD, not as an AI-assistance tool for human readers in diagnosis. While the technology involves proprietary software for target identification, the clinical trials focus on the overall clinical outcome of the therapy itself, rather than how the AI component improves human diagnostic performance.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance)
The device, the Magnus Neuromodulation System (MNS) with SAINT Technology, is a treatment system that includes proprietary software for individualized target identification. It's not a standalone diagnostic algorithm. The "SAINT Technology" itself is described as "the combination of using the specific individualized target for treatment along with a proprietary accelerated treatment protocol." Therefore, it inherently involves human medical professionals for its application ("intended for use by trained medical professionals"). The performance data presented are for the entire system in a clinical treatment context, not for the algorithm in isolation.
7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)
The "ground truth" for the effectiveness of the SAINT Technology is established through clinical outcomes data using validated psychiatric rating scales and predefined criteria:
- Montgomery-Asberg Depression Rating Scale (MADRS):
- Response: ≥50% reduction in MADRS score.
- Remission: MADRS score ≤10.
- Hamilton Depression Rating Scale (HDRS-17) / (HDRS-6):
- Response: ≥50% reduction in HDRS score.
- Remission: HDRS-17 score ≤7 or HDRS-6 score ≤4.
Safety is assessed by monitoring and reporting Adverse Events (AEs), including Serious Adverse Events (SAEs).
8. The Sample Size for the Training Set
The document does not specify a separate "training set" for the clinical performance evaluation of the device in the way a machine learning model would have one. The clinical studies (1-4) are the evaluation (test) sets for the device's clinical efficacy and safety.
However, the "proprietary software informed by structural and functional MRI" that "identify the individualized target within the L-DLPFC for stimulation" would have, by its nature, been developed and trained using various datasets. The size and nature of such internal development/training datasets for the software component are not provided in this summary.
9. How the Ground Truth for the Training Set Was Established
As mentioned above, information regarding a specific "training set" for the software component is not detailed in this 510(k) summary. For software that generates individualized targets, the "ground truth" for its development would typically be established based on:
- Neuroanatomical models and expert neuroimaging knowledge: Defining correct anatomical and functional regions in the brain.
- Clinical correlation: Data linking specific MRI features (structural and functional connectivity patterns) to treatment response in previous studies (either published literature or internal pilot data).
This summary focuses on the clinical validation of the entire system as a treatment, assuming the target identification software was developed using robust, scientifically sound methods prior to these clinical trials.
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September 1, 2022
Magnus Medical, Inc. Susan Noriega VP Regulatory Affairs 1350 Old Bayshore Highway, Suite 600 Burlingame, CA 94010
Re: K220177
Trade/Device Name: Magnus Neuromodulation System (MNS) with SAINT Technology, Model Number 1001K Regulation Number: 21 CFR 882.5805 Regulation Name: Repetitive Transcranial Magnetic Stimulation System Regulatory Class: Class II Product Code: OBP Dated: August 2, 2022 Received: August 2, 2022
Dear Susan Noriega:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's
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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
for Pamela Scott Assistant Director DHT5B: Division of Neuromodulation and Physical Medicine Devices OHT5: Office of Neurological and Physical Medicine Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) [not yet assigned] K220177
Device Name
Magnus Neuromodulation System (MNS) with SAINT® Technology
Indications for Use (Describe)
The Magnus Neuromodulation System with SAINT Technology is indicated for the treatment of Maior Depressive Disorder (MDD) in adult patients who have failed to achieve satisfactory improvement from prior antidenressant medication in the current episode.
Type of Use (Select one or both, as applicable)
| Prescription Use (Part 21 CFR 801 Subpart D) |
|---|
| Over-The-Counter Use (21 CFR 801 Subpa |
| Over-The-Counter Use (21 CFR 801 Subpart C)
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510(k) Summary Provided in Accordance with 21 CFR §807.92(c)
magnusmedical
| Date Summary Prepared: | August 30, 2022 |
|---|---|
| 510(k) Number: | K220177 |
| 510(k) Owner: | Magnus Medical, Inc.1350 Old Bayshore Highway, Suite 600Burlingame CA 94010 USA(415) 690-7358 |
| Submitter and Official Contact: | Susan NoriegaMagnus Medical, Inc.1350 Old Bayshore Highway, Suite 600Burlingame CA 94010 USAsusan@magnusmed.com(650) 793-1966 |
| Trade Name: | Magnus Neuromodulation System (MNS) with SAINTTechnology |
| Common Name: | Transcranial Magnetic Stimulation Device |
| Classification Name: | Repetitive Transcranial Magnetic Stimulator for Treatmentof Major Depressive Disorder |
| Primary Classification Regulation: | 21 CFR §882.5805 |
| Primary Product Code: | OBP |
| Secondary Classification and Code: | 21 CFR §882.1870/GWF21 CFR §882.4560/HAW |
| Substantially Equivalent Device: | Nexstim Navigated Brain Therapy (NBT) System 2Nexstim PlcHelsinki, FinlandPremarket Notification K182700Cleared on March 22, 2019 |
| Device Description: | The Magnus Neuromodulation System (MNS) with SAINTTechnology is a non-invasive repetitive transcranialmagnetic stimulation (rTMS) system that deliversindividualized and navigationally directed repetitivemagnetic pulses to the left dorsolateral prefrontal cortex (L- |
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DLPFC) to treat Major Depressive Disorder (MDD) in adult patients who have failed to achieve satisfactory improvement from prior antidepressant medication in the current episode.
The MNS with SAINT Technology is available for prescription use only and is intended for use by trained medical professionals in either an inpatient or outpatient setting.
The Magnus Neuromodulation System consists of hardware devices (stimulator with treatment coil and neuronavigation system) intended to deliver SAINT Technology; that is, rTMS (as intermittent theta burst stimulation (iTBS)) to a target area within the L-DLPFC along with proprietary software informed by structural and functional MRI and designed to identify the individualized target within the L-DLPFC for stimulation. Also included in the system are a coil and monitor for motor threshold determination, which is used to inform patient-specific stimulation settings. SAINT Technology is the combination of using the specific individualized target for treatment along with a proprietary accelerated treatment protocol that condenses treatment to five days. The Magnus Neuromodulation System is designed to support successful delivery of SAINT Technology.
The Magnus Neuromodulation System with SAINT Intended Use: Technology is intended for the delivery of SAINT neuromodulation therapy to treat major depressive disorder (MDD) in adult patients who have failed to achieve satisfactory improvement from prior antidepressant medication in the current episode.
Technology Comparison:
The Magnus Neuromodulation System with SAINT Technology has the same intended use and technological characteristics as the predicate device.
Compatible Hardware: The Magnus Neuromodulation System is a complete set of mutually compatible hardware components that have been specifically selected and evaluated to safely and effectively deliver SAINT Technology in conjunction with the Magnus Cloud Software. The following includes the set of hardware components included with the Magnus Neuromodulation System:
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| Item | Qty | Magnus Part # | Supplier Name/Model | Supplier Part # | 510(k) Clearance |
|---|---|---|---|---|---|
| Stimulator | 1 | 1002 | MagVenture/X100 | 9016E0711 | K173620 |
| Treatment Coil | 1 | 1003 | MagVenture/Cool-B65 | 9016E0491 | K171967 |
| Motor Threshold Coil | 1 | 1004 | MagVenture/C-B60 | 9016E0673 | K171967 |
| Coil Arm | 1 | 1005 | MagVenture/Super FlexibleArm | 9016B0181 | K173620 |
| Stimulator Cart | 1 | 1006 | MagVenture/Trolley withHolding Arrangements | 9016B0383 | K173620 |
| Isolation Transformer | 1 | 1007 | MagVenture/IsolationTransformer | 9016D0031 | K173620 |
| Cooling System | 1 | 1008 | MagVenture/Coil Cooler Unit | 9016B0151 | K173620 |
| Evoked ResponseMonitor | 1 | 1009 | MagVenture/MEP Monitor | 9016C0711 | K162873 |
| NeuronavigationSystem withaccessories (cart andPC) | 1 | 1010 | Brain Science Tools(Soterix)/Neural Navigator | HD-SWN(nav)HD-SWTA(cart)HD-SWAPC(pc) | K191422 |
MagVenture devices and accessories are supplied by Tonica Elektronik / MagVenture Brain Science Tools Neural Navigator is supplied by Soterix Medical
All hardware components were utilized in non-clinical bench performance testing as included in their respective 510(k) clearances. Stimulator, Treatment Coil, Motor Threshold Coil, Coil Arm, Stimulator Cart, Isolation Transformer, Cooling System, and Evoked Response Monitor hardware components were additionally utilized in clinical performance testing.
| Table 1: Technology Comparison for the Magnus Neuromodulation System vs. the Predicate | |||
|---|---|---|---|
| Device | |||
| Predicate Device | Proposed Device | Notes | |
| Characteristic | Nexstim NBT System 2K182700 | Magnus NeuromodulationSystem with SAINTTechnology | |
| Intended Use | The Nexstim NavigatedBrain Therapy (NBT)System 2 is intended for thetreatment of majordepressive disorder in adultpatients who have failed toachieve satisfactoryimprovement from prior | The MagnusNeuromodulation System(MNS) with SAINTTechnology is intended forthe delivery of SAINTneuromodulation therapy totreat major depressivedisorder (MDD) in adult | No difference |
| Predicate Device | Proposed Device | Notes | |
| antidepressant medication inthe current episode. | patients who have failed toachieve satisfactoryimprovement from priorantidepressant medication inthe current episode. | ||
| Main SystemHardware | • TMS Stimulator• Motor Threshold andTreatment Coil• Tracking System for coilpositioning• Evoked response monitorfor motor thresholddetermination• Cooling Unit | • TMS Stimulator• Treatment Coil• Tracking System for coilpositioning• Evoked response monitorfor motor thresholddetermination• Cooling Unit• Motor Threshold Coil | The predicate devicecombines motor thresholdmeasurement and stimulationtreatment in one coil whilethe Magnus System utilizestwo separate dedicatedpurpose coils. |
| Treatment TargetIdentification | Proprietary software utilizingstructural MRI to assist inlocating the target areawithin the L-DLPFC fordepression therapy. | Proprietary software utilizingstructural and functionalMRI data to locate the targetarea within the L-DLPFC fordepression therapy. | The Magnus System usesfunctional MRI connectivitydata in addition to structuralMRI data to inform theindividual treatment targetlocalization software. BothMagnus and predicatemethods aid in localizationof appropriate target areaswithin the L-DLPFC forstimulation and bothmethods provide moreindividual specificity thanthe historically used externalanatomical landmarks. |
| Treatment CoilPositioning | Real time visualization of thetreatment target relative tothe treatment coil positionvia a tracking system(neuronavigation system) | Real time visualization of thetreatment target relative tothe treatment coil positionvia a tracking system(neuronavigation system) | No difference |
| Motor ThresholdDetermination | Visual inspection of fingermovement + EMG | Visual inspection of fingermovement + EMG | No difference |
| Treatment IntensityDetermination | Motor threshold andelectrical field model is usedto adjust stimulationintensity | Motor threshold and depth-correction is used to adjuststimulation intensity | Nexstim and Magnus bothprimarily rely on MT todetermine treatmentintensity. Nexstim also usesa proprietary electrical fieldmodel to orient the rotationof the coil, while Magnususes a depth correction toadjust for differences indistance between motorcortex and frontal cortex atthe target. |
| StimulationProtocol | 10 Hz and iTBS | iTBS | The MagnusNeuromodulation Systemwith SAINT Technologyuses only iTBS; the 10 Hzprotocol is not needed for theMagnus System |
| Predicate Device | Proposed Device | Notes | |
| Area of BrainStimulated | L-DLPFC | L-DLPFC | No difference |
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Treatment Protocol Comparison: The Magnus Neuromodulation System with SAINT Technology utilizes the same type of treatment (intermittent theta burst stimulation/iTBS) as the predicate device but with more pulses (90,000 vs. 18,000) delivered over a shorter period of time (five days vs. six weeks) thus allowing for a more rapid response and more flexibility in terms of where treatment can be delivered; the more compressed schedule makes acute inpatient treatment more feasible.
| Table 2: Treatment Protocol Comparison of SAINT Technology iTBS vs. Predicate iTBS | |||
|---|---|---|---|
| TreatmentParameter | Nexstim NBT System 2K182700(predicate device) | MagnusNeuromodulationSystem with SAINTTechnology (proposeddevice) | Notes |
| StimulationDose | 600 pulses persession/day, 12,000-18,000 pulses total | 1,800 pulses persession, 18,000 pulsesper day, 90,000 pulsestotal | The number of pulses and timing ofsessions are optimized for effectivenessand compressed treatment schedule withno impact on safety. |
| Magnetic FieldIntensity | 120% Motor Threshold | 90% Motor Threshold | iTBS administered at amplitudes less than100% of motor threshold may be saferand more focal, and may be moreeffective than iTBS at amplitudes greaterthan 100% motor threshold. |
| PulseFrequency | 50 Hz | 50 Hz | No difference |
| Pulses perburst | 3 | 3 | No difference |
| BurstFrequency | 5 Hz | 5 Hz | No difference |
| Stimulus TrainDuration | 2 seconds | 2 seconds | No difference |
| Inter-trainInterval | 8 seconds | 8 seconds | No difference |
| MagneticPulses perSession | 600 | 1800 | |
| TreatmentSessionDuration | 3.3 minutes | 10 minutes | The number of pulses and timing ofsessions are optimized for effectiveness |
| TreatmentSessions perDay | 1 | 10 | and compressed treatment schedule withno impact on safety. |
| TreatmentSessions perWeek | 5 | 50 |
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| TreatmentParameter | Nexstim NBT System 2K182700(predicate device) | MagnusNeuromodulationSystem with SAINTTechnology (proposeddevice) | Notes |
|---|---|---|---|
| TotalTreatmentMinutes | 99 | 500 | |
| TotalTreatmentSessions | 30 | 50 | |
| TotalTreatmentPulses | 18,000 | 90,000 | |
| TreatmentDuration | 6 weeks | 5 days | Shorter total treatment duration than thepredicate is possible because of anoptimized and compressed treatmentschedule. |
Summary of Performance Data:
Sterilization and Shelf Life: The Magnus Neuromodulation System with SAINT Technology is not provided as a sterile device and is not intended for sterilization by the user. The shelf life and/or useful life of the hardware components are as indicated in their respective labeling and instructions for use. Software components will have updates managed as appropriate by Magnus Medical or its suppliers and therefore do not have a defined useful life at this time. Biocompatibility: Patient contact materials that are part of the Magnus Neuromodulation System were tested and are compliant with ISO 10993-1, Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process. Software for the Magnus Neuromodulation System with SAINT Software: Technology was designed and developed in accordance with current FDA guidance and industry standards including IEC 62304, Medical Device Software – Software lifecycle processes and ISO 14971, Application of risk management to medical devices. Hardware: The hardware components of the Magnus Neuromodulation System have undergone all applicable electrical safety, electromagnetic compatibility, performance, and usability testing required.
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Clinical: Clinical testing was performed to provide assurance of safety and effectiveness of the Magnus Neuromodulation System with SAINT Technology. The system was evaluated in four clinical studies, three open-label and one randomized and sham controlled. Data from these studies are summarized in the following tables:
| Title of Study | Number ofParticipants | Summary of Results |
|---|---|---|
| High-dose Spaced theta-burst TMSas a Rapid-acting Antidepressant inHighly Refractory Depression1 | 6 | 5/6 (83.3%) responded (≥50% decrease in HamiltonDepression Rating Scale (HDRS-17) and 4/6 remitted(HDRS<7) with no serious adverse events. |
| Stanford Accelerated IntelligentNeuromodulation Therapy forTreatment Resistant Depression2 | 21 | 19/21 (90.5%) of participants met remission criteria (score<11 on the Montgomery-Asberg Depression Rating Scale[MADRS]) with no serious adverse events or negativecognitive side effects. |
| Stanford Neuromodulation Therapy(SNT): A Double-BlindRandomized Controlled Trial3 | 29 (14 active,15 sham) | 12/14 (85.7%) in the active treatment group met responsecriteria (≥50% reduction in MADRS) and 11/14 (78.6%) metremission criteria (MADRS ≤10) vs 4/15 (27%) in the shamgroup met response criteria and 2/15 (13.3%) remitted. Thestudy was terminated early based on clear superiority of activetreatment vs. sham at the planned interim analysis. No seriousadverse events were reported. |
| An Open Label Pilot Trial to Assessthe Feasibility of Using the MagnusNeuromodulation System (MNS)with Magnus IntelligentNeuromodulation Therapy (MINT4)as a Maintenance Treatment forDepression | 14 | 13/14 (92.8%) of subjects responded (≥50% reduction inMADRS) and 11/14 (78.6%) met remission criteria (MADRS≤10) after the initial 5 days of treatment. No serious adverseevents have been reported. |
Table 3: Summary of Clinical Studies Performed with SAINT Technology
Data from four clinical trials using SAINT Technology have demonstrated similar clinical outcomes with equivalent results as compared to the predicate device.
Demographic and effectiveness data are presented separately for the each of the four SAINT studies and compared to the published iTBS data5 in Table 4. Patient demographics in terms of severity of depression and resistance to depression are comparable for the SAINT and THREE-D
3 Cole EJ, Phillips AL, Bentzley BS, et al. Am J Psychiatry. 2021 Oct 29:appiajp202120101429. doi: 10.1176/appi.ajp.2021.20101429. Epub ahead of print. PMID: 34711062.
4 Williams NR, Sudheimer KD, Bentzley BS, et al., High-dose spaced theta-burst TMS as a rapid-acting antidepressant in highly refractory depression. Brain 2018;141:1-5.
2 Cole EJ, Stimpson KH, Bentzley BS, at al., Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment Resistant Depression. Am J Psychiatry 2020;177:716-726.
4 Note that MINT, SNT, and SAINT all refer to the same combination of target identification and treatment delivery that is SAINT Technology.
5 Blumberger DM et al. Effectiveness of theta burst vs. high-frequency repeitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomized non-inferiority trial. Lancet 2018;391:1683-92.
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populations and the outcomes for SAINT trials, both open-label and randomized controlled trials, demonstrate equivalent effectiveness as compared to the results from the THREE-D trial without introduction of any new safety concerns.
| SAINT Technology Compared to the Predicate iTBS (THREE-D) | Study #1 | Study #2 | Study #3 | Study #4 | THREE-D* |
|---|---|---|---|---|---|
| # of Subjects | 6 | 22 (21 per protocol) | 29(15 active/14 sham) | 14 | 209 active |
| Baseline Characteristics | |||||
| Age (mean) | 56 | 45 | 49/52 | 52 | 42 |
| Age (range) | 38-69 | 19-78 | 27-73 | 23-82 | 18-65 |
| Gender (% female) | 67% | 57% | 34% | 50% | 59% |
| Maudsley StagingMethod Score (mean) | 14 | 10 | 9/9 | 9.5 | 6.3 |
| # having prior TMS | 6 | 7 (only 1 previouslyremitted) | 0 | - | 0 |
| # having prior ECT | 6 | 0 | 0 | - | 16 |
| # having prior VNS | 1 | 0 | 0 | - | 0 |
| MADRS at baseline(mean) | 40.3 | 34.86 | 31/35 | 32 | - |
| HDRS at baseline(mean) | 16 (6-item)28.8 (17-item) | 13.9 (6-item)25.9 (17-item) | 14/15 (6-item)24/26 (17-item) | 12.5 (6-item) | 23.7 (17-item) |
| Type of Study | Single arm,Open label | Single armOpen label | Randomized,blinded | Single armOpen label | Randomized,Open label |
| Treatment Arms | Single, active | Single, active | 2 arms - active(n=14) vs.sham (n=15) | Single, active | 2 arms - 10 HzrTMS (n=205)vs. iTBS(n=209) |
| Treatment | 5 days SAINTiTBS | 5 days SAINTiTBS | 5 days SAINTiTBS vs. 5 dayssham SAINT | 5 days SAINTiTBS | 4-6 weeks 10Hz rTMS vs. 6weeks iTBS |
| Outcome | |||||
| Response(MADRS reduction≥50%) | 83.3%(assessed at endof 5 days oftreatment) | 90.5%(assessed at endof 5 days oftreatment) | 85.7% activevs. 26.7% sham(assessedduring themonth aftertreatment) | 92.8%(assessedduring theweek aftertreatment) | - |
| Remission (MADRS≤10) | 83.3%(assessed at endof 5 days oftreatment) | 90.5%(assessed at endof 5 days oftreatment forthe 21 perprotocolsubjects) | 78.6% activevs. 13.3% sham(assessedduring themonth aftertreatment) | 78.6%(assessedduring theweek aftertreatment) | - |
| Response (HDRSreduction ≥50%) | 83.3% | 86.4 %(HDRS-17) | - | 71.4% (HDRS-6) | 49% (HDRS-17) |
| Study #1 | Study #2 | Study #3 | Study #4 | THREE-D* | |
| of 5 days oftreatment) | 81.8% (HDRS-6) | ||||
| 66.7% | 77.3% (HDRS-17) | ||||
| Remission (HDRS-17≤7 or HDRS-6 ≤4) | (assessed at endof 5 days oftreatment) | 81.8% (HDRS-6) | 57.1% (HDRS-6) | 32% (HDRS-17) | |
| Serious AdverseEvents | 0 | 0 | 0 | 0 | 3 (1%) |
| Comments | The single non-respondingsubject waslaterdetermined tohave a primarydiagnosis ofOCD | 23 subjectsrecruited, 1ineligible, 1withdrew ontreatment day 1because ofanxiety | The trial wasterminated atthe plannedinterim analysisdue to thesuperiority ofthe activetreatment | This trial isongoing |
Table 4: Summary of Demographic and Effectiveness Data for Clinical Studies Performed with SAINT Technology Compared to the Predicate iTBS (THREE-D)
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*The predicate device, Nexstim Navigated Brain Therapy (NBT) System 2, relied on the THREE-D Clinical Study data for clearance, via its own predicate (K173620).
Note: The clinical performance data for the Magnus Neuromodulation System (MNS) with SAINT Technology were obtained from a total of 70 patients enrolled in four clinical trials (one randomized double-blind, sham-controlled study and three open-label studies) conducted in close geographical proximity. As a result of studies being performed at a single site, generalizability to the broader United States population has not been evaluated.
Note: The Magnus Neuromodulation System (MNS) with SAINT Technology has been evaluated at four weeks post treatment in all four clinical trials. Effectiveness has not been established beyond the timepoints evaluated in the four clinical studies.
Note: Blinding Assessment Study #3
The adequacy of blinding utilized in the investigation was assessed by asking participants to guess their treatment allocation and to report their confidence in their guess (on a scale of 1 to 5) on the last day of treatment. This guess and confidence level were translated to a guess metric that ranged from 0 (participant had full confidence that he or she received the sham treatment) to 1 (participant had full confidence he or she received the active treatment). Twenty-three (23) participants provided guesses as to which treatment they received, and 19 indicated their confidence in their guess. One-way t tests indicated no significant differences from chance (chance guess metric=0.50) in the sham (mean guess metric=0.39, p=0.56) and active (mean guess metric=0.43, p=0.52) treatment groups. Because not all participants indicated their confidence in their guess, binomial tests were also used to determine whether the number of correct guesses exceeded chance. Binomial tests indicated no significant differences from chance in proportion of correct guesses in the sham (6 of 10 correct, p=0.38) and active (7 of 13 correct, p=0.50) treatment groups. Finally, linear regression analysis detected no relationship between the guess metric and the change in depression severity as indicated by magnitude of proportional change in MADRS scores (=0.11. p=0.66). Since only 19 of 29 participants completed both parts of the blinding assessment. uncertainty remains as to the adequacy of the blinding for the remainder of the study population.
Adverse events from the Study #3 active treatment arm and the open label study (Study #4) of SAINT are listed in Table 5 below along with the adverse events reported in the THREE-D iTBS Study. (Note that Study #1 and Study #2 are not shown in the table, because these universitybased studies did not formally tabulate non-serious adverse events; zero serious adverse events were observed in either study.) All the adverse events reported for SAINT are similar to those
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reported for THREE-D iTBS in type and incidence with the exception that fatigue is reported more frequently with SAINT, likely because of the increased time spent in the clinic for the five days of SAINT treatment. Notably, rates of fatigue were the same for active and sham SAINT groups.
| Event | Number participants reporting event (%)6 | ||
|---|---|---|---|
| SAINT n=14 (active armfrom Study #3) | SAINT n=14 (Study #4) | iTBS (THREE-D) n=209 | |
| Headache | 8 (57%) | 6 (43%) | 136 (65%) |
| Nausea | - | - | 14 (7%) |
| Dizziness | - | 1 (7%) | 18 (9%) |
| Unrelated medicalproblem | - | 5 (36%) | 46 (22%) |
| Fatigue | 8 (57%) | 5 (36%) | 16 (8%) |
| Insomnia | - | 5 (36%) | 10 (5%) |
| Anxiety or agitation | 4 (29%) | 2 (14%) | 9 (4%) |
| Back or neckpain/discomfort | 7 (50%) | 3 (21%) | 6 (3%) |
| Unrelated accidents | - | 1 (7%) | 3 (1%) |
| Vomiting | - | - | 1 (<1%) |
| Tinnitus | - | 2 (14%) | 3 (1%) |
| Migraine aura | - | - | 4 (2%) |
| Abnormal sensations | - | - | 4 (2%) |
| Pain/discomfort attreatment site | 5 (36%) | 4 (29%) | - |
| Other head/neck areapain | 3 (21%) | 3 (21%) | - |
| Any serious adverseevents | 0 | 0 | 3 (1%) |
Table 5: Adverse Events: SAINT compared to THREE-D iTBS
In summary, the clinical study results indicate that iTBS delivered using the Magnus Neuromodulation System with SAINT Technology is safe, effective, and substantially equivalent to iTBS delivered using the predicate device, the Nexstim NBT System 2 (K182700), and without introduction of any new risks or safety concerns.
Conclusion: The Magnus Neuromodulation System (MNS) with SAINT Technology has equivalent hardware components, the same general principle for target identification, the same intended use, and the same technological features as the predicate device. The Magnus Neuromodulation System (MNS) with SAINT Technology does not raise any new issues of safety and effectiveness and is substantially equivalent to the predicate device.
6 Shown here are outcomes from the active SAINT arm (Study #3), active SAINT (Study #4), and the iTBS arm from the THREE-D study.
§ 882.5805 Repetitive transcranial magnetic stimulation system.
(a)
Identification. A repetitive transcranial magnetic stimulation system is an external device that delivers transcranial repetitive pulsed magnetic fields of sufficient magnitude to induce neural action potentials in the prefrontal cortex to treat the symptoms of major depressive disorder without inducing seizure in patients who have failed at least one antidepressant medication and are currently not on any antidepressant therapy.(b)
Classification. Class II (special controls). The special control is FDA's “Class II Special Controls Guidance Document: Repetitive Transcranial Magnetic Stimulation System.” See § 882.1(e) for the availability of this guidance document.