CONFIDENTIAL — CONTAINS PROPRIETARY INFORMATION OF SOLSTICE BIOMEDICAL DEVICES LTD. NOT FOR PUBLIC DISCLOSURE
PRE-SUBMISSION MEETING PACKAGE
PROPOSED CLINICAL STUDY PROTOCOL SUMMARY
Solstice Lumina™ Continuous Glucose Monitoring System Lumina C14 Implantable Sensor and Lumina R7 Wearable Reader/Transmitter
Protocol Number: SBD-LUM-CL-001 Protocol Title: "LUMINA-US"
Prepared by: Calderwood & Harkness LLP 1401 K Street NW, Suite 900 Washington, D.C. 20005
On behalf of: Solstice Biomedical Inc. 220 Westbrook Drive, Suite 400 Cambridge, MA 02142
Date: June 16, 2025
Prepared for Submission to: U.S. Food and Drug Administration Center for Devices and Radiological Health (CDRH) Office of Health Technology 2 (OHT2) Division of Chemistry and Toxicology Devices
Document Classification: Pre-Submission (Q-Sub) Meeting Package — Section 5
Confidential — Contains proprietary information of Solstice Biomedical Devices Ltd.
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1. Introduction and Purpose
This section of the Pre-Submission (Q-Sub) meeting package provides a clinical study protocol synopsis for Protocol SBD-LUM-CL-001 ("LUMINA-US"), a prospective, multicenter clinical study designed to generate clinical evidence supporting a traditional 510(k) premarket notification submission covering both the Lumina C14 implantable continuous glucose monitoring sensor and the Lumina R7 wearable reader/transmitter, evaluated and cleared as a complete, integrated system. The clinical study protocol described herein has been developed in consultation with the Sponsor's regulatory affairs, clinical operations, biostatistics, and quality assurance teams, with input from external regulatory consultants and regulatory counsel. This protocol synopsis is submitted in advance of the requested Pre-Submission meeting to facilitate meaningful dialogue with the U.S. Food and Drug Administration ("FDA") regarding the clinical study design, primary and secondary endpoints, statistical analysis plan, and regulatory pathway considerations.
The LUMINA-US study is specifically intended to evaluate three critical dimensions of device performance: (i) sensor accuracy, as measured by Mean Absolute Relative Difference ("MARD") and Consensus (Clarke) Error Grid Analysis against established laboratory and fingerstick reference glucose methods; (ii) safety, as assessed through systematic monitoring of device-related adverse events, sensor insertion site reactions, and device malfunctions; and (iii) user labeling comprehension, including the ability of representative intended users to correctly follow sensor insertion instructions, interpret real-time glucose readings and trend arrows, and respond appropriately to hypo- and hyperglycemia alerts generated by the system.
The Solstice Lumina™ Continuous Glucose Monitoring System has been commercially available in the European Union since September 2024, following issuance of EU Medical Device Regulation (MDR) CE Certificate No. MCA-2024-07319, dated September 12, 2024, by Meridian Conformity Assessment GmbH (Notified Body No. 0483), an EU-recognized Notified Body with competence in active implantable and in vitro diagnostic medical devices. The EU clinical evaluation and post-market clinical follow-up plan supporting the CE marking included clinical performance data collected from a European multicenter accuracy study (Protocol SBD-LUM-EU-001, n = 225 subjects), which demonstrated an overall MARD of 8.2% across the full 14-day sensor wear period and a Clarke Error Grid Zones A+B rate of 99.4%. These EU clinical data are referenced as supportive evidence in the overall regulatory strategy; however, the LUMINA-US study described herein is designed as a standalone U.S. clinical study adequate to independently support the 510(k) submission.
Solstice Biomedical Inc. (State of Delaware, File No. 7834291), a wholly owned U.S. subsidiary of Solstice Biomedical Devices Ltd. (Ireland, Companies Registration Office No. 648231), is the intended 510(k) holder and the clinical study sponsor. Solstice Biomedical Inc. was incorporated in Delaware on March 8, 2023, and maintains its principal office at 220 Westbrook Drive, Suite 400, Cambridge, Massachusetts 02142. The U.S. subsidiary serves as the legal entity responsible for all U.S. regulatory submissions, clinical study sponsorship obligations, and post-market activities. The parent company, Solstice Biomedical Devices Ltd., headquartered at Unit 14, Liffey Innovation Park, Chapelizod, Dublin D20 FX72, Ireland, retains responsibility for product development, manufacturing, and global regulatory strategy.
The purpose of presenting this protocol synopsis within the Pre-Submission meeting package is to seek FDA feedback on the following: (a) the adequacy of the proposed clinical study design, including the single-arm, paired-measurement accuracy study methodology; (b) the appropriateness of the primary and secondary study endpoints, including the MARD performance target; (c) the sufficiency of the proposed sample size and statistical analysis plan; (d) the acceptability of the Investigational Device Exemption (IDE) regulatory pathway analysis, specifically whether the study qualifies for the diagnostic device IDE exemption under 21 C.F.R. § 812.2(c)(3) or, alternatively, as a Non-Significant Risk (NSR) investigation under 21 C.F.R. § 812.2(b); and (e) any additional study design elements, safety monitoring requirements, or labeling comprehension assessment methodologies that FDA would recommend.
The proposed 510(k) submission will reference the following predicate devices: (i) primary predicate: NovaSense GlucoTrack NX-500 Continuous Glucose Monitoring System (510(k) No. K211034, cleared June 18, 2022, product code QKQ), which established substantial equivalence for a subcutaneously implanted electrochemical CGM sensor with a wearable reader/transmitter for continuous glucose monitoring in adults with diabetes mellitus; and (ii) secondary predicate: NovaSense GlucoTrack NX-700 Continuous Glucose Monitoring System (510(k) No. K230489, cleared March 7, 2024, product code QKQ), which established additional predicate support for a 14-day sensor wear duration with Bluetooth Low Energy data transmission and configurable glucose alerts. Both predicate devices are classified under 21 C.F.R. § 862.1355 (Glucose test system) and were assigned product code QKQ (Electrode, Glucose, Subcutaneous). The Solstice Lumina™ CGM System shares the same intended use, technological characteristics, and performance expectations as these predicate devices, and the clinical data generated by the LUMINA-US study is expected to demonstrate that the Solstice Lumina™ CGM System is at least as safe and effective as the identified predicates.
2. Sponsor Information
The following entities and individuals are responsible for the sponsorship, regulatory oversight, and conduct of the LUMINA-US clinical study:
Sponsor / 510(k) Applicant:
Solstice Biomedical Inc. 220 Westbrook Drive, Suite 400 Cambridge, MA 02142 United States Telephone: (617) 555-4200
VP of U.S. Operations:
Marcus Hale Primary U.S. operational contact for regulatory correspondence, site agreements, and study logistics. Mr. Hale serves as the designated point of contact for FDA communications related to the Pre-Submission meeting and subsequent regulatory interactions. Mr. Hale reports directly to the CEO of the parent company and coordinates with the VP of Regulatory Affairs at Dublin headquarters.
Sponsor's Parent Company:
Solstice Biomedical Devices Ltd. Unit 14, Liffey Innovation Park Chapelizod, Dublin D20 FX72 Ireland Telephone: +353 (1) 555-7800
CEO:
Dr. Eoin Gallagher, Ph.D. Dr. Gallagher serves as Chief Executive Officer of Solstice Biomedical Devices Ltd. and is responsible for overall corporate strategy, including the U.S. market entry plan for the Lumina™ CGM System. Dr. Gallagher has over 20 years of experience in medical device development and commercialization, with prior leadership roles at several European medical device companies focused on diabetes management technologies.
VP of Regulatory Affairs (Sponsor Representative for this Protocol):
Dr. Niamh Tierney, RAC Based at Dublin HQ. Dr. Tierney holds Regulatory Affairs Certification (RAC) from the Regulatory Affairs Professionals Society and serves as the Sponsor's designated regulatory representative for the LUMINA-US clinical study protocol. Dr. Tierney is responsible for regulatory strategy development, protocol review, and interactions with regulatory authorities, including FDA and EU Notified Bodies. Dr. Tierney led the EU MDR conformity assessment process that resulted in CE marking of the Solstice Lumina™ CGM System in September 2024.
Chief Technology Officer:
Dr. Aisling Burke, Ph.D. Dr. Burke oversees all aspects of device engineering, firmware and algorithm development, and manufacturing technology for the Lumina™ CGM System. Dr. Burke's team is responsible for the proprietary PtIr-4G electrode coating technology, the LuminaPredict algorithm, and all software verification and validation activities. Dr. Burke is available to address technical questions raised by FDA during the Pre-Submission meeting.
Quality Assurance Director:
Fiona Drennan Ms. Drennan oversees the quality management system for Solstice Biomedical Devices Ltd. in accordance with ISO 13485:2016 and 21 C.F.R. Part 820. Ms. Drennan is responsible for ensuring that clinical study devices are manufactured, released, and tracked in accordance with applicable quality system requirements and that all clinical study documentation meets quality standards.
Regulatory Counsel:
Calderwood & Harkness LLP 1401 K Street NW, Suite 900 Washington, D.C. 20005 United States
• Miriam Calloway — Responsible Partner
• Amy Whitfield — Lead Associate
• Sean Morrissey — Working Associate
Calderwood & Harkness LLP provides regulatory counsel to Solstice Biomedical Inc. with respect to the 510(k) premarket notification strategy, Pre-Submission meeting preparation, IDE/NSR analysis, clinical study agreement review, and overall FDA regulatory compliance. Calderwood & Harkness LLP prepared this Pre-Submission meeting package on behalf of the Sponsor.
Regulatory Consultancy:
Pinnacle Regulatory Consulting Group LLC 9500 Medical Center Drive, Suite 210 Rockville, MD 20850 United States
• Dr. Sandra Ellison — Managing Director
• Thomas Greenbaum — Senior Regulatory Specialist
Engagement commenced January 15, 2025. Pinnacle Regulatory Consulting Group LLC provides technical regulatory consulting services, including predicate device analysis, substantial equivalence assessment, clinical study design consultation, and preparation of 510(k) submission components. Dr. Ellison has over 25 years of experience advising medical device companies on FDA submissions for in vitro diagnostic and continuous monitoring devices, including multiple CGM systems.
3. Device Description Summary
3.1 Solstice Lumina™ CGM System Overview
The Solstice Lumina™ Continuous Glucose Monitoring System ("Solstice Lumina™ CGM System" or "Lumina System") is a two-component integrated system comprising the Lumina C14 implantable sensor and the Lumina R7 wearable reader/transmitter. These two components work together to provide continuous, real-time glucose monitoring for persons with diabetes mellitus. The Lumina C14 sensor is inserted subcutaneously and measures interstitial fluid glucose concentrations using enzymatic electrochemical biosensing technology. The Lumina R7 wearable reader/transmitter receives glucose measurement data wirelessly from the C14 sensor via Bluetooth Low Energy (BLE) communication, processes the data using the LuminaPredict proprietary algorithm, and displays real-time glucose values, trend arrows, and trend graphs to the user. The system is also capable of communicating with the Solstice Lumina™ mobile application installed on a compatible smartphone or tablet.
The anticipated product code for the Solstice Lumina™ CGM System is QKQ (Electrode, Glucose, Subcutaneous), consistent with the product code assigned to the primary and secondary predicate devices. The anticipated regulatory classification is Class II, under 21 C.F.R. § 862.1355 (Glucose test system).
Intended Use: The Solstice Lumina™ CGM System is intended for continuous glucose monitoring in persons aged 18 years and older with Type 1 or Type 2 diabetes mellitus. The system is intended to replace fingerstick blood glucose testing for diabetes treatment decisions, including insulin dosing. The system is indicated for use by patients at home and in healthcare settings. The system is intended for single-patient use and is a prescription device.
The Lumina System provides real-time glucose measurements, glucose trend information (including directional trend arrows and graphical trend display), and configurable alerts for hypo- and hyperglycemic conditions. The system is not intended for use in critically ill patients, for diagnosis of diabetes mellitus, or in persons under 18 years of age.
3.2 Lumina C14 Implantable Sensor
The Lumina C14 is a subcutaneously implantable continuous glucose monitoring sensor designed for insertion into the subcutaneous tissue of the upper arm using a proprietary single-use applicator device (the "Lumina Applicator"). The sensor is designed for a maximum wear duration of 14 days (336 hours) before replacement with a new sensor.
The C14 sensor employs a fourth-generation enzymatic electrochemical biosensor architecture featuring the proprietary platinum-iridium electrode coating, designated "PtIr-4G" technology. This electrode coating is a key differentiating feature of the Lumina System and was developed to enhance signal stability, reduce interference from common electroactive species (including acetaminophen, ascorbic acid, and uric acid), and extend functional sensor life. The PtIr-4G electrode coating is a multi-layer structure consisting of a platinum-iridium alloy base electrode, an enzymatic sensing layer containing glucose oxidase, an interference-rejection membrane, and a biocompatible outer membrane designed to minimize foreign body response and tissue encapsulation during the 14-day wear period.
Key technical specifications of the Lumina C14 sensor include:
• Sensor wear duration: 14 days (336 hours)
• Wireless data transmission: Bluetooth Low Energy (BLE) 5.2
• Measurement range: 40–400 mg/dL
• Warm-up time: ≤ 60 minutes from sensor insertion to first glucose reading
• Glucose measurement interval: Every 1 minute (internal measurement); glucose value transmitted to the R7 reader/transmitter every 5 minutes
• Sensor insertion depth: 5.0 mm ± 0.5 mm subcutaneous
• Sensor filament material: Platinum-iridium alloy with PtIr-4G coating
• Sensor filament diameter: 0.35 mm
• Applicator: Single-use, spring-loaded automatic insertion applicator; ethylene oxide (EO) sterilized
• Software: Lumina Firmware v3.4.2; LuminaPredict Algorithm v2.1
The LuminaPredict Algorithm v2.1 is an embedded software algorithm that processes raw electrochemical signals from the C14 sensor and converts them into calibrated glucose concentration values. The algorithm incorporates signal processing, noise filtering, drift compensation, temperature correction, and predictive trending functions. The algorithm has been validated against reference glucose values in benchtop and clinical testing, including the EU multicenter clinical study (Protocol SBD-LUM-EU-001). The algorithm does not require fingerstick calibration by the user during the 14-day sensor wear period (factory-calibrated).
3.3 Lumina R7 Wearable Reader/Transmitter
The Lumina R7 is an arm-worn reader/transmitter device designed to be worn on the upper arm in proximity to the implanted C14 sensor. The R7 receives real-time glucose data from the C14 sensor via BLE 5.2 communication, processes the received data, and presents the information to the user through an integrated display and audible/haptic alerts.
The R7 reader/transmitter features include:
• Display: Real-time glucose values (displayed in mg/dL), directional trend arrows (indicating the rate and direction of glucose change), and 8-hour glucose trend graphs
• Configurable alerts: User-configurable hypo- and hyperglycemia alert thresholds with audible, visual, and haptic notification modalities; alert latency ≤ 5 minutes from sensor measurement to user notification
• Connectivity: Communicates with the Solstice Lumina™ mobile application (compatible with iOS 15.0 and later; Android 12.0 and later) via BLE for data display, storage, and sharing with healthcare providers
• Battery: Rechargeable lithium-polymer battery; battery life ≥ 14 days on a single charge under normal operating conditions
• Water resistance: IP67 rated
• Weight: Approximately 28 grams (including adhesive patch)
• Software: Lumina Reader OS v2.1.0; Lumina Mobile App v1.0.3
The Lumina Mobile App provides additional functionality including extended glucose trend history (up to 90 days), glucose statistics and reports (time in range, average glucose, glucose management indicator), data sharing with healthcare providers via the Solstice Lumina™ cloud platform, and integration with compatible insulin delivery systems (future feature, not included in the initial 510(k) submission scope).
The Lumina R7 reader/transmitter is designed for reusable operation across multiple sensor wear periods and has an expected service life of approximately 2 years under normal use conditions.
4. Study Synopsis
4.1 Protocol Identification
The protocol version will be finalized and dated following the Pre-Submission meeting with FDA, currently targeted for August 14, 2025. Any substantive modifications to the study design, endpoints, or statistical analysis plan resulting from FDA feedback will be incorporated into Protocol Version 1.0 prior to finalization. The protocol will be submitted to the Clearwater Institutional Review Board for review and approval prior to study initiation.
4.2 Study Design
Design: The LUMINA-US study is a prospective, single-arm, multicenter clinical study conducted at six (6) U.S. clinical sites. The study is designed to evaluate the accuracy, safety, and user labeling comprehension of the Solstice Lumina™ CGM System in adults with Type 1 or Type 2 diabetes mellitus.
No control arm: The study employs a single-arm design in which each enrolled subject serves as his or her own reference. Accuracy is assessed through paired sensor glucose measurements and reference glucose measurements obtained concurrently from the same subject. There is no comparator device arm and no randomization. This design is appropriate because the primary study objective is to characterize the measurement accuracy of the Lumina System against an established reference standard, rather than to compare the Lumina System to another CGM device or to evaluate a therapeutic intervention.
Reference methods: Glucose reference values for accuracy assessment will be obtained using two complementary reference methods:
(a) In-clinic accuracy sessions: Adriatic Partners LLC (YSI) 2900 Biochemistry Analyzer (or equivalent laboratory glucose analyzer meeting the analytical performance requirements specified in the protocol) will be used as the primary reference glucose method during supervised in-clinic accuracy sessions. Venous blood samples will be collected at approximately 15-minute intervals during 10–12 hour in-clinic sessions and analyzed immediately on the YSI analyzer. The YSI analyzer is a well-established laboratory reference method for CGM accuracy studies and is consistent with the reference methods used in predicate device clinical studies.
(b) Home-use period: During the home-use periods between in-clinic sessions, subjects will perform daily fingerstick capillary blood glucose measurements using an FDA-cleared blood glucose meter (model to be specified in the final protocol) to generate additional paired sensor–reference data points under real-world use conditions.
Rationale for single-arm design: The proposed single-arm, paired-measurement accuracy study design is consistent with FDA-recognized study designs for CGM accuracy studies, as reflected in the FDA guidance document "Integrated Continuous Glucose Monitoring Systems" (September 2023). This guidance document describes the clinical study design expectations for CGM systems seeking marketing authorization, including the use of paired sensor–reference glucose measurements for MARD calculation and Clarke Error Grid Analysis. The single-arm design is also consistent with the clinical study designs that supported the clearance of the primary and secondary predicate devices (NovaSense GlucoTrack NX-500, 510(k) No. K211034, and NovaSense GlucoTrack NX-700, 510(k) No. K230489). Solstice believes that the proposed study design is adequate to generate the clinical evidence necessary to support a substantial equivalence determination.
4.3 Study Objectives
4.3.1 Primary Objective. The primary objective of the LUMINA-US study is to evaluate the accuracy of the Solstice Lumina™ CGM System by determining the Mean Absolute Relative Difference (MARD) between glucose values reported by the Lumina System and corresponding reference glucose values obtained from the YSI 2900 analyzer (in-clinic sessions) and fingerstick blood glucose meter (home-use sessions).
The MARD performance target for the primary objective is an overall MARD of ≤ 9.0%, calculated across all glucose concentration ranges (40–400 mg/dL) and across the full 14-day sensor wear period. This performance target is consistent with FDA's current expectations for integrated continuous glucose monitoring (iCGM) classification, as articulated in the FDA guidance document "Integrated Continuous Glucose Monitoring Systems" (September 2023), and is consistent with the accuracy performance demonstrated by the predicate devices at the time of their clearance. The 9.0% MARD target represents a clinically meaningful level of accuracy that supports the intended use of the Lumina System for diabetes treatment decisions, including insulin dosing.
4.3.2 Secondary Objectives. The secondary objectives of the LUMINA-US study are designed to provide a comprehensive characterization of device performance, safety, and usability:
(a) Clarke Error Grid Analysis: Evaluate the proportion of paired sensor–reference glucose data points falling within Zones A and B of the Consensus (Clarke) Error Grid Analysis. The performance target is ≥ 99% of all paired data points falling within Zones A+B. Data points in Zone A represent clinically accurate measurements (within 20% of the reference value for glucose ≥ 70 mg/dL, or within 20 mg/dL for glucose < 70 mg/dL). Data points in Zone B represent measurements that would not lead to inappropriate treatment decisions.
(b) Sensor functional life: Evaluate sensor functional life over the full 14-day (336-hour) wear duration by determining the proportion of sensors that remain functional and continue to provide glucose readings throughout the intended 336-hour sensor wear period. Sensor survival will be assessed using Kaplan-Meier methodology, and the proportion of sensors completing the full wear period will be reported.
(c) Device safety: Assess the safety of the Solstice Lumina™ CGM System by systematically monitoring and documenting all device-related adverse events, including but not limited to: sensor insertion site reactions (pain, erythema, edema, bruising, bleeding, infection, scarring, allergic or irritant contact dermatitis), systemic reactions, device malfunctions, and any other adverse events that occur during the 14-day sensor wear period and the 7-day post-removal follow-up period.
(d) User labeling comprehension: Evaluate user labeling comprehension by assessing subjects' ability to correctly follow sensor insertion instructions, interpret real-time glucose readings and trend arrows displayed on the R7 reader/transmitter, and respond appropriately to hypo- and hyperglycemia alerts. Labeling comprehension will be assessed using validated questionnaires administered at pre-use (screening or Day 0 visit) and post-use (Day 14 visit) time points, with a target of ≥ 90% correct responses on key comprehension items.
4.4 Study Endpoints
4.4.1 Primary Endpoint. The primary endpoint of the LUMINA-US study is the overall Mean Absolute Relative Difference (MARD) between sensor glucose values and reference glucose values, calculated across all glucose concentration ranges (40–400 mg/dL) and across the full 14-day sensor wear period. MARD is calculated as the mean of the absolute values of the relative differences between each paired sensor glucose measurement and the corresponding reference glucose measurement, expressed as a percentage. For reference glucose values below 70 mg/dL, absolute difference (in mg/dL) may be reported in addition to relative difference, consistent with established conventions for CGM accuracy assessment.
The pre-specified success criterion for the primary endpoint is that the upper bound of the 95% confidence interval (CI) for the overall MARD must be ≤ 9.0%.
4.4.2 Key Secondary Endpoints. The key secondary endpoints are:
1. MARD stratified by glucose concentration range:
• Hypoglycemic range: < 70 mg/dL
• Euglycemic range: 70–180 mg/dL
• Hyperglycemic range: > 180 mg/dL
2. MARD stratified by day of sensor wear:
• Days 1–3 (early wear period, including sensor stabilization)
• Days 4–7 (mid-early wear period)
• Days 8–10 (mid-late wear period)
• Days 11–14 (late wear period, approaching end of sensor life)
3. Percentage of paired data points in Clarke Error Grid Zones A, B, C, D, and E, with the pre-specified success criterion that ≥ 99% of paired data points fall within Zones A+B combined.
4. Sensor survival rate: Proportion of sensors completing the full 336-hour wear period, analyzed using Kaplan-Meier methodology with censoring for non-device-related discontinuations.
5. Incidence and severity of device-related adverse events: Tabulated by event type (insertion site reactions, systemic reactions, device malfunctions, other), severity (mild, moderate, severe), and causality (related, possibly related, unrelated).
6. User labeling comprehension scores: Percentage of subjects achieving ≥ 90% correct responses on the pre-use and post-use labeling comprehension questionnaires, analyzed separately for key comprehension domains (sensor insertion, glucose value interpretation, trend arrow interpretation, alert response).
4.5 Study Population
4.5.1 Enrollment Target. The total planned enrollment for the LUMINA-US study is 350 subjects, distributed equally between the two diabetes types:
• 175 subjects with Type 1 diabetes mellitus (T1D)
• 175 subjects with Type 2 diabetes mellitus (T2D)
This balanced enrollment is intended to ensure adequate representation of both diabetes types in the accuracy analysis and to enable stratified analyses by diabetes type. The sample size was determined based on statistical power calculations (described in Section 10.1) and is consistent with the sample sizes used in clinical studies supporting the clearance of the predicate devices.
Enrollment will be distributed across the six clinical sites to achieve geographic and demographic diversity representative of the intended use population. The Sponsor and CRO will implement enrollment monitoring procedures to ensure appropriate representation of both diabetes types and to avoid excessive concentration of enrollment at any single site.
4.5.2 Key Inclusion Criteria. Subjects must meet all of the following criteria to be eligible for enrollment:
1. Age ≥ 18 years at the time of informed consent.
2. Confirmed diagnosis of Type 1 or Type 2 diabetes mellitus, documented in the subject's medical record.
3. Currently receiving insulin therapy (multiple daily injections or continuous subcutaneous insulin infusion) or oral antidiabetic medications (or a combination thereof) for at least 3 months prior to screening.
4. Glycated hemoglobin (HbA1c) between 6.0% and 12.0%, inclusive, measured at the screening visit or within 30 days prior to screening using a laboratory-based HbA1c assay.
5. Willing and able to comply with all study procedures for the 14-day sensor wear period, including attendance at all scheduled in-clinic accuracy sessions, daily fingerstick blood glucose measurements during the home-use period, and completion of study questionnaires.
6. Able to provide written informed consent in English prior to any study-related procedures.
4.5.3 Key Exclusion Criteria. Subjects meeting any of the following criteria will be excluded from enrollment:
1. Known allergy or hypersensitivity to adhesives, medical-grade adhesive tapes, or any component material of the Lumina CGM System, including but not limited to platinum, iridium, sensor membrane materials, or the adhesive patch material.
2. Skin conditions at proposed sensor insertion sites (upper arm) that would interfere with sensor placement, adhesion, or clinical assessment of insertion site reactions, including but not limited to: dermatitis, psoriasis, eczema, excessive scarring, lipodystrophy, or tattoos at the insertion site.
3. Current participation in another clinical study involving an investigational drug, device, or biologic, or participation in such a study within 30 days prior to screening.
4. Pregnancy, currently breastfeeding, or intent to become pregnant during the study period. Female subjects of childbearing potential must have a negative urine pregnancy test at screening.
5. Use of acetaminophen (paracetamol) at doses exceeding 1 gram per day on a regular basis. Acetaminophen is a known potential interferent with electrochemical glucose sensing technology and may affect sensor accuracy. Occasional use of acetaminophen at doses ≤ 1 g/day is permitted, provided it is documented in the subject's diary.
6. Severe renal impairment, defined as estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m², calculated using the CKD-EPI equation at screening.
7. Medical conditions that may interfere with study glucose monitoring or confound the interpretation of study results, including but not limited to: current dialysis treatment, hydroxyurea therapy, severe anemia (hemoglobin < 8 g/dL), or any condition known to cause clinically significant discrepancies between interstitial and blood glucose concentrations.
8. Any condition or circumstance that, in the opinion of the investigator, would make the subject unsuitable for study participation or would compromise the subject's ability to comply with study procedures.
4.6 Clinical Study Sites
The LUMINA-US study will be conducted at six (6) U.S. clinical sites. Sites will be selected from academic medical centers, endocrinology/diabetes specialty clinics, and clinical research centers with demonstrated experience in conducting CGM clinical trials and device accuracy studies.
Sites will be geographically distributed across the United States to ensure that the enrolled study population is demographically diverse and representative of the intended use population, including adequate representation of racial and ethnic minorities, a range of ages, and a mix of urban and suburban/rural populations. The Sponsor and CRO will implement a site selection process that includes the following qualification criteria:
• Prior experience conducting CGM accuracy studies or similar medical device clinical trials
• Availability of a Adriatic Partners LLC (YSI) 2900 Biochemistry Analyzer or equivalent laboratory glucose analyzer that meets the analytical performance specifications required by the study protocol
• Adequate research infrastructure, including research staff, dedicated clinic space, laboratory facilities, electronic data capture capabilities, and regulatory document management systems
• Availability of a qualified Principal Investigator (physician with expertise in diabetes/endocrinology) and adequate clinical research staff (study coordinators, phlebotomists, clinical research nurses)
• Institutional capacity to enroll and retain the required number of subjects within the planned enrollment period
• Institutional willingness to accept central IRB oversight from Clearwater Institutional Review Board (or, where institutional policies require local IRB review, willingness to coordinate with the central IRB)
Site initiation visits will be conducted by the CRO (Veltrano Clinical Research Organization Inc.) prior to study initiation to ensure that each site meets all qualification criteria, that all required regulatory documents (IRB approval, informed consent, investigator agreements, financial disclosure forms) are in place, and that site staff have been trained on all study procedures.
4.7 Study Duration and Timeline
Estimated total study duration: Approximately 6 months from first subject enrolled to clinical study report completion.
The major phases and estimated durations are as follows:
• Enrollment period: Approximately 14 weeks, during which all 350 subjects are expected to be enrolled across the 6 clinical sites. This assumes an average enrollment rate of approximately 4–5 subjects per site per week.
• Per-subject sensor wear period: 14 days (336 hours) of active sensor wear, plus a 7-day post-removal follow-up period (total per-subject study duration approximately 21 days).
• Data analysis and database lock: Approximately 8 weeks after the last subject last visit (LSLV), during which all study data will be entered, verified, queried, resolved, and locked. Statistical analyses will be performed on the locked database.
Key milestone dates:
• Planned study start (first subject enrolled): September 15, 2025, subject to receipt of FDA Pre-Submission meeting feedback and IRB approval prior to study initiation.
• Planned enrollment completion: Approximately late December 2025.
• Planned last subject last visit: Approximately mid-February 2026.
• Planned database lock: Approximately mid-March 2026.
• Planned study completion (clinical study report): March 15, 2026.
These timelines are estimates and are subject to change based on FDA feedback from the Pre-Submission meeting, IRB review timelines, site activation timelines, and enrollment pace. The Sponsor will provide updated timelines as appropriate.
4.8 Study Procedures Overview
The following is a summary of the major study procedures. Detailed procedures, visit schedules, and data collection requirements will be specified in the full study protocol (Appendix A).
Screening Visit:
The screening visit will occur within 30 days prior to the sensor insertion visit (Day 0). At the screening visit, the following procedures will be performed: informed consent discussion and signing of the informed consent form; collection of demographic information and medical history; review of inclusion and exclusion criteria; HbA1c measurement (if not performed within 30 days prior to screening); urine pregnancy test for female subjects of childbearing potential; assessment of potential sensor insertion sites on the upper arm; and baseline skin assessment. Subjects who meet all inclusion criteria and none of the exclusion criteria will be eligible for enrollment and scheduling of the Day 0 sensor insertion visit.
Sensor Insertion Visit (Day 0):
At the Day 0 visit, the following procedures will be performed: confirmation of continued eligibility; insertion of the Lumina C14 sensor subcutaneously into the posterior upper arm using the Lumina Applicator; application of the Lumina R7 reader/transmitter to the upper arm in proximity to the C14 sensor; sensor warm-up period (≤ 60 minutes); training of the subject on device use, including interpretation of glucose values, trend arrows, and alerts, operation of the R7 reader/transmitter, and use of the Lumina Mobile App (if applicable); provision of study supplies (blood glucose meter, test strips, lancets, sensor diary, adverse event diary); and administration of the pre-use labeling comprehension questionnaire.
In-Clinic Accuracy Sessions:
At least three (3) in-clinic accuracy sessions will be conducted for each subject during the 14-day sensor wear period, scheduled on Days 1, 7, and 14 (± 1 day). Each in-clinic session will last approximately 10–12 hours, during which frequent venous blood glucose sampling will be performed for YSI reference glucose analysis. Paired sensor–reference glucose measurements will be obtained at intervals of approximately 15 minutes throughout each in-clinic session, yielding approximately 40–48 paired data points per session. During each in-clinic session, subjects will be managed to include periods of euglycemia, hyperglycemia (induced by meal challenges or reduced insulin dosing under medical supervision), and, where clinically safe and feasible, mild hypoglycemia (achieved through controlled insulin dosing under close medical supervision with glucose available for rescue). The goal of the glucose manipulation protocol is to obtain an adequate number of paired data points across the full measurement range (40–400 mg/dL), including the clinically important hypoglycemic range.
Home-Use Period:
Between in-clinic accuracy sessions, subjects will wear the C14 sensor and R7 reader/transmitter continuously at home. During the home-use period, subjects will perform daily fingerstick capillary blood glucose measurements using the provided blood glucose meter for additional paired sensor–reference data. Subjects will be instructed to log any device issues, adverse events, or sensor alerts in the study diary. Subjects will continue their usual diabetes management regimen (insulin therapy, oral antidiabetic medications, diet, and exercise) as directed by their personal healthcare provider; the study does not alter subjects' diabetes treatment.
Sensor Removal Visit (Day 14 or Sensor End-of-Life):
At the Day 14 visit (or earlier if the sensor reaches end-of-life or is discontinued for any reason), the following procedures will be performed: final in-clinic accuracy session (if Day 14); sensor removal; insertion site assessment (evaluation of erythema, edema, pain, infection, scarring, or other local reactions using a standardized scoring system); adverse event evaluation; collection of the R7 reader/transmitter and any unused study supplies; and administration of the post-use labeling comprehension questionnaire.
Labeling Comprehension Assessment:
The user labeling comprehension assessment will consist of validated questionnaires administered at two time points: (i) at screening or Day 0 (pre-use questionnaire), assessing subjects' ability to correctly follow sensor insertion instructions, interpret glucose values and trend arrows, and understand alert functions based on the device labeling and instructions for use provided to them; and (ii) at Day 14 (post-use questionnaire), assessing subjects' comprehension of the same domains after 14 days of device use. The questionnaires will cover key comprehension domains including sensor insertion technique, glucose value interpretation, trend arrow interpretation, hypo/hyperglycemia alert response, and device troubleshooting. The target is for ≥ 90% of subjects to achieve ≥ 90% correct responses on the key comprehension items.
Follow-Up:
A follow-up contact (telephone call or in-person visit, at the investigator's discretion) will be conducted 7 days (± 2 days) after sensor removal to assess for any delayed insertion site reactions, including delayed hypersensitivity reactions, infection, or persistent skin irritation. Any adverse events identified during the follow-up period will be documented and reported in accordance with the study safety monitoring plan.
5. Contract Research Organization
The Sponsor has engaged a contract research organization (CRO) to support the operational conduct of the LUMINA-US clinical study.
CRO: Veltrano Clinical Research Organization Inc.
Address: 500 North Capitol Street, Suite 700, Indianapolis, IN 46204
Key Contact: Dr. Lisa Fontaine, VP of Clinical Operations
Dr. Fontaine will serve as the primary CRO contact for the LUMINA-US study and will be responsible for overseeing all aspects of CRO-managed study operations. Dr. Fontaine has over 15 years of experience in clinical trial management for medical device studies, including extensive experience with in vitro diagnostic and continuous monitoring device studies.
CRO Responsibilities:
Veltrano Clinical Research Organization Inc. will be responsible for the following activities under the LUMINA-US study:
• Site selection and qualification: Identification, assessment, and qualification of clinical study sites in accordance with the site qualification criteria described in Section 4.6; conduct of site initiation visits.
• Study monitoring: Assignment of trained clinical research associates (CRAs) for routine monitoring visits, interim monitoring visits, and close-out visits; source data verification; protocol compliance oversight; and investigator site file maintenance.
• Data management: Implementation and management of a validated, 21 C.F.R. Part 11–compliant electronic data capture (EDC) system for clinical data collection, query generation and resolution, medical coding (MedDRA for adverse events), and database management.
• Statistical analysis: Performance of pre-specified statistical analyses in accordance with the Statistical Analysis Plan, including MARD calculations, Clarke Error Grid analyses, sensor survival analyses, safety data tabulations, and labeling comprehension analyses.
• Regulatory document management: Management of essential regulatory documents, including IRB correspondence, investigator agreements, financial disclosure forms, and regulatory submission documents.
• Safety reporting support: Assistance with the collection, processing, and reporting of adverse events, serious adverse events, and unanticipated adverse device effects in accordance with applicable regulatory requirements.
• Study close-out: Conduct of site close-out visits, reconciliation of study supplies and investigational devices, final data verification, and archiving of study records.
Clinical study budget (estimated): $4,200,000 (based on 350 subjects at an estimated per-subject cost of $12,000, which includes all CRO management fees, clinical monitoring, data management, statistical analysis, and operational support). This budget estimate is subject to adjustment based on final site budgets, enrollment pace, and any protocol amendments resulting from FDA Pre-Submission meeting feedback.
CRO agreement: A comprehensive master services agreement (MSA) between Solstice Biomedical Inc. and Veltrano Clinical Research Organization Inc. is currently under review by Calderwood & Harkness LLP. The MSA covers, among other provisions: scope of services and detailed task orders; payment milestones and invoicing terms; intellectual property ownership and data access rights; regulatory compliance obligations, including compliance with 21 C.F.R. Parts 11, 50, 56, and 812, as applicable; data integrity requirements; confidentiality and non-disclosure provisions; indemnification and limitation of liability; insurance requirements; representations and warranties; dispute resolution; and termination provisions. The MSA is expected to be fully executed prior to study initiation.
6. Institutional Review Board
Central IRB: Clearwater Institutional Review Board LLC
Address: 3200 Bayshore Boulevard, Tampa, FL 33629
IRB Registration No.: IRB-2019-04821
Clearwater Institutional Review Board LLC is an independent, commercial institutional review board registered with the U.S. Department of Health and Human Services, Office for Human Research Protections (OHRP), and is accredited by the Association for the Accreditation of Human Research Protection Programs (AAHRPP). Clearwater IRB has extensive experience reviewing protocols for medical device clinical studies, including CGM and other diabetes device studies.
IRB Approval Strategy: The Sponsor proposes a central IRB approval model, with Clearwater Institutional Review Board LLC serving as the IRB of record for all six (6) U.S. clinical study sites. This centralized model is intended to promote consistency in human subjects protection review, streamline the review process, and avoid unnecessary duplication of effort. Where site-specific institutional requirements mandate local IRB review (e.g., at academic medical center sites with established institutional review requirements), the Sponsor will coordinate with the local IRB and Clearwater IRB to establish an appropriate reliance arrangement or co-review process, consistent with applicable regulations and institutional policies.
Required submissions to Clearwater IRB: The following study documents will be submitted to Clearwater IRB for review and approval prior to study initiation:
• Study protocol (Protocol SBD-LUM-CL-001, Version 1.0)