R-TF-015-004 Clinical Investigation Plan

Scope

The purpose of this Clinical Investigation Plan (CIP) is to set out the rationale, objectives, design, methodology, conduct, implementation, record-keeping and the method of analysis for the clinical investigation.

CIP Identification

	CIP
Title of the clinical investigation	Pilot study for the clinical validation of artificial intelligence algorithms for the quantification of severity and monitoring of the evolution of patients with FFA (Frontal Fibrosing Alopecia)
Device under investigation	Legit.Health Plus
Protocol version	Version 9.0
Date	07/02/2026
Protocol code	LEGIT_AFF_EVCDAO_2026x
Sponsor	AI LABS GROUP, S.L (Legit.Health)
Coordinating Investigator	Dr. Daniel Ortega Quijano
Principal Investigator(s)	Dr. Daniel Ortega Quijano
Collaborating Investigator(s)	Dr. David Saceda, Dr. Óscar Muñoz, Dra. Ángela Hermosa, Dr. Sergio Vañó, Alfonso Medela, Andy Aguilar, Taig Mac Carthy, Ignacio Hernández
Investigational site(s)	Hospital Universitario Ramón y Cajal
Ethics Committee	Comité de Ética de la Investigación -CEI- del Hospital Universitario Ramón y Cajal

Table of contents

• Scope
• CIP Identification
• Compliance statement
• Abbreviations and Definitions
• CIP or protocol specifications
  • Principal Investigator
  • Coordinating Investigator(s)
  • Collaborating Investigator(s)
  • Investigational sites
  • Funding
• Product Identification and Description
  • Device accountability
• Justification of the design
  • Background and rationale
  • Evaluation of preclinical and clinical data
• Hypothesis
• Objectives
  • Primary objetive(s)
  • Secondary objective(s)
• Summary of the study
• Design and Methods
  • Type of clinical research
  • Population
  • Duration
  • Acceptance criteria
  • Inclusion and exclusion criteria
  • Variables
  • Condition of interest
  • Quality control
  • Limitations of clinical research
• Ethical considerations
  • Data confidentiality
  • Information to subjects and informed consent
  • Bias minimization measures
  • Calendar
  • Monitoring plan
  • Subject follow-up procedures
  • Completition of the investigation
  • Statistical analysis
  • Procedures
  • Data management
• CIP Modification
• CIP Deviations
• Start, follow-up and end reports
• Statements of compliance
• Adverse events, adverse product reactions and product deficiencies
  • Adverse Events (AE) and Adverse Event to Product (AEP)
  • Product deficencies
  • Serious Adverse Events, serios adverse events to product and serious and unexpected adverse event to the product
  • Non-reportable Adverse Events
  • Notification Process
  • Foreseeable adverse events and adverse events to product
  • Emergency contact
  • Data Monitoring Committee (DMC)
• Vulnerable population (if applicable)
• Suspension or early termination of clinical research
• Publication policy
• Bibliography

Compliance statement

The clinical investigation will be conducted according to the Clinical Investigation Plan (CIP) and other applicable guidances and regulations. This includes compliance with:

• The ethical principles originating from the World Medical Association's Declaration of Helsinki
• Harmonized standard UNE-EN ISO 14155:2020
• Regulation (EU) 2017/745 on medical devices (MDR), including the applicable General Safety and Performance Requirements (GSPR) as outlined in Annex I, and the requirements of Annex XV (Chapter I and Chapter II, Section 3)
• Harmonized standard UNE-EN ISO 13485:2016
• MDCG 2024-3 for its structural and content expectations, MDCG 2021-8 concerning application requirements, and MDCG 2020-10/1 Rev 1 for safety reporting timelines and definitions
• Regulation (EU) 2016/679 (GDPR)
• Spanish Organic Law 3/2018 on the Protection of Personal Data and guarantee of digital rights.

All data processing within the device is carried out in accordance with the highest standards of data protection and privacy. Patient information is managed in an encrypted manner to ensure confidentiality and security.

The research team assumes the role of Data Controller, responsible for the collection and management of study data. Legit.Health acts as the Data Processor and is not involved in the processing of patient data.

The storage and transfer of data comply with European data protection regulations. At the conclusion of the study, all information stored in the device will be permanently and securely deleted.

The device employs robust technical and organizational security measures to safeguard personal data against unauthorized access, alteration, loss, or processing.

Abbreviations and Definitions

• AE: Adverse Event
• AEMPS: Spanish Agency of Medicines and Medical Devices
• AEP: Adverse Reaction to Product
• AUC: Area Under the ROC Curve
• CAD: Computer-Aided Diagnosis
• CMD: Data Monitoring Committee
• CIP: Clinical Investigation Plan
• CUS: Clinical Utility Questionnaire
• DLQI: Dermatology Quality of Life Index
• GCP: Standards of Good Clinical Practice
• ICH: International Conference of Harmonization
• IFU: Instructions For Use
• IRB: Institutional Review Board
• N/A: Not Applicable
• NCA: National Competent Authority
• PI: Principal Investigator
• PPV: Positive Predictive Value
• NPV: Negative Predictive Value
• SAE: Serious Adverse Events
• SAEP: Serious Adverse Event to Product
• SUAEP: Serious and Unexpected Adverse Event to the Product
• SUS: System Usability Scale

CIP or protocol specifications

Principal Investigator

Dr. Daniel Ortega Quijano Dermatology Service University Hospital Ramón y Cajal Carretera Colmenar Viejo, S/N Km 9, 28034 MADRID

Coordinating Investigator(s)

Dr. Daniel Ortega Quijano Dermatology Service University Hospital Ramón y Cajal

Collaborating Investigator(s)

• Dr. David Saceda (Dermatology Service)
• Dr. Óscar Muñoz (Dermatology Service)
• Dra. Ángela Hermosa (Dermatology Service)
• Dr. Sergio Vañó (Dermatology Service)
• Alfonso Medela (AI LABS GROUP, S.L.)
• Andy Aguilar (AI LABS GROUP, S.L.)
• Taig Mac Carthy (AI LABS GROUP, S.L.)
• Ignacio Hernández (AI LABS GROUP, S.L.)

Investigational sites

University Hospital Ramón y Cajal Carretera Colmenar Viejo, S/N Km 9, 28034 MADRID

Funding

Sponsor: AI LABS GROUP, S.L. No external funding sources are anticipated.

Product Identification and Description

	Information
Device name	Legit.Health Plus (hereinafter, the device)
Model and type	NA
Version	1.1.0.0
Basic UDI-DI	8437025550LegitCADx6X
Certificate number (if available)	MDR 792790
EMDN code(s)	Z12040192 (General medicine diagnosis and monitoring instruments - Medical device software)
GMDN code	65975
EU MDR 2017/745	Class IIb
EU MDR Classification rule	Rule 11
Novel product (True/False)	TRUE
Novel related clinical procedure (True/False)	TRUE
SRN	ES-MF-000025345

Device accountability

Given that the investigational device is a Software as a Medical Device (SaMD), product accountability is managed through strict access control to the platform. Access to the software is granted exclusively to authorized investigators and registered patients during the clinical investigation through secure credentials (username and password). The sponsor will maintain a log of all active accounts and usage metrics associated with the clinical investigation. Upon completion, early termination, or temporary halt of the study, or if a user withdraws consent, their access credentials will be immediately revoked to prevent further use. Malfunctioning software versions or "expired" access rights are similarly managed by restricting access and disabling accounts, ensuring no unauthorized or obsolete product use occurs.

Justification of the design

Background and rationale

Frontal fibrosing alopecia (FFA) was first described in 1994 as a form of lymphocytic cicatricial alopecia characterized by selectively affecting the frontotemporal hairline and eyebrows. The pathogenesis, histology, and treatments for this disease are still to be definitively determined. FFA occurs mostly in postmenopausal white women, suggesting a hormonal origin, though it can also affect individuals of any ethnicity, premenopausal women, and even men.

Patients with FFA usually present an advancing recession of the frontotemporal hairline, which progresses around 0.6 and 1.1 cm per year. Trichoscopy reveals a reduction in the follicular ostia, as well as follicular hyperkeratosis and perifollicular erythema.

Patient-reported outcome (PRO) scoring system questionnaires play a fundamental role in the treatment of affected patients. The evaluation of the hairline recession (HLR) is considered the most appropriate and objective measure of severity. To evaluate the severity of FFA, different scoring systems are used, primarily using systems or questionnaires like the Severity of Alopecia Tool III (SALT III), the FFA Global Staging Score, the perifollicular erythema classification, the count of shed hairs, and the classification of hairline recession patterns.

However, the methods currently used to quantify, stage or measure the involvement of patients present major limitations. The most undeniable limitation is the inherent difficulty for humans to quantify parameters objectively, stably, and precisely. This is where Artificial Intelligence (AI) and Computer-Aided Diagnosis (CAD) algorithms provide immense value. AI allows an automatic and more precise quantification of visual signs and severity. The study aims to clinically validate a novel AI tool by Legit.Health Plus for the automatic counting of hairs to assess FFA severity.

Evaluation of preclinical and clinical data

These evaluations can be consulted in the T-015-005 Investigator's brochure.

Hypothesis

The hypothesis guiding this study is that the algorithm of the medical device with artificial intelligence developed by AI LABS GROUP S.L. is capable of quantifying the severity and tracking the evolution of frontal fibrosing alopecia (FFA). This is based on the notion that AI introduces significant changes in the diagnosis and monitoring process:

1. Automated counting of the number of hairs to estimate capillary density and determine the severity of FFA.
2. Automated determination of the severity and follow-up of the evolution associated with the pathology. In short, the tool is capable of recognizing follicles with high precision in trichoscopic images and counting them, calculating hair density (hairs per cm²), thereby offering less inter-observer variability, greater sensitivity to change, and better interpretability.

Objectives

Primary objetive(s)

The main objective of the present study is to validate that the algorithm developed by Legit.Health is capable of measuring the severity of frontal fibrosing alopecia by means of automatic hair counting and to verify that it does so with a capacity equal to or superior to the respective "gold standard" filled in by the specialist, obtaining the following value:

• MAPE (Mean Absolute Percentage Error) equal to or less than 10% for the counting of hair shafts.

Secondary objective(s)

The secondary objective includes:

• Validation of the automatic hair segmentation algorithm, so that when compared with the respective gold standard, the following value is obtained:
  • F1 Score greater than or equal to 70% in hair segmentation.

Summary of the study

This is a prospective observational diagnostic validation study of a case series. It aims to include 100 adult patients (≥ 18 years) with frontal fibrosing alopecia treated at the Dermatology Service of the Hospital Universitario Ramón y Cajal. The recruitment period is estimated at 12 months. The total duration of the study is estimated at 24 months, with each patient participating for 12 months.

Design and Methods

Type of clinical research

Prospective observational diagnostic test validation study of a case series.

Population

Adult patients (≥ 18 years) with frontal fibrosing alopecia treated at the Dermatology Service of the Hospital Universitario Ramón y Cajal.

Duration

Recruitment period: 12 months. Total study duration: 24 months, including database closure, analysis, and final report preparation. Duration of participation of each patient: 12 months from the date of inclusion.

Acceptance criteria

• MAPE (Mean Absolute Percentage Error) equal to or less than 10% for the counting of hair shafts.
• F1 Score greater than or equal to 70% in hair segmentation.

Inclusion and exclusion criteria

Inclusion Criteria (Patients):

• Patients with frontal fibrosing alopecia diagnosed following the guidelines established by the International FFA Cooperative Group.
• Patients aged 18 years or older.
• Patients who have signed the informed consent of the study.

Inclusion Criteria (Data):

• Images that exceed a score of 70 in the Dermatology Image Quality Assessment (DIQA).

Exclusion Criteria (Patients):

• Patient who, at the investigator's discretion, will not comply with the study procedures.

Exclusion Criteria (Data):

• Images that do not exceed a score of 70 in the Dermatology Image Quality Assessment (DIQA).

Variables

Primary Variable:

• Number of hair shafts. The algorithm's performance, trained with trichoscopic images, will be measured by comparing its detections with human annotations.

Secondary Variables:

• Demographic data: sex, age and phototype.
• Clinical data: patient code, inclusion date, previous diseases, pregnancy, menopause, facial sunscreen use, diagnosis, diagnosis date, start circumstances, and triggers.
• FFA Global Staging Score.
• Severity of Alopecia Tool III (SALT III) score.
• Classification of perifollicular erythema.
• Classification of the number of shed hairs.
• Classification of frontal hairline recession patterns (linear, diffuse, pseudo-fringe).
• Hair segmentation: classification of each pixel in hair and non-hair categories.

Condition of interest

Quantification of severity and monitoring of Frontal Fibrosing Alopecia (FFA).

Quality control

The Principal Investigator is responsible for reviewing and approving the study protocol and ensuring data quality. Data will be entered into an electronic Database using double data entry by collaborating investigators. Validation processes using computerized filters based on validation rules will be executed to identify missing or incongruent values.

Limitations of clinical research

The main limitation is the quantity and quality of the collected images. Variability in illumination, color, shape, size, and focus are determinant. High intra-patient variability combined with an insufficient number of images could lead to lower precision.

Ethical considerations

This study adhered to international Good Clinical Practice (GCP) guidelines, the Declaration of Helsinki in its latest amendment, and applicable international and national regulations. As applicable, approval from the relevant Ethics Committee was obtained prior to the initiation of the study. When applicable, modifications to the protocol were reviewed and approved by the Principal Investigator (PI) and subsequently evaluated by the Ethics Committee before subjects were enrolled under a modified protocol.

This study was conducted in compliance with European Regulation 2016/679, of 27 April, concerning the protection of natural persons with regard to the processing of personal data and the free movement of such data (General Data Protection Regulation, GDPR), and Organic Law 3/2018, of 5 December, on the Protection of Personal Data and the guarantee of digital rights. In accordance with these regulations, no data enabling the personal identification of participants was collected, and all information was managed securely in an encrypted format.

Participants were informed both orally and in writing about all relevant aspects of the study, with the information being tailored to their level of understanding. They were provided with a copy of the informed consent form and the accompanying patient information sheet. Adequate time was given to patients to ask questions and fully comprehend the details of the study before providing their consent.

The PI was responsible for the preparation of the informed consent form, ensuring it included all elements required by the International Conference on Harmonisation (ICH), adhered to current regulatory guidelines, and complied with the ethical principles of GCP and the Declaration of Helsinki.

The original signed informed consent forms were securely stored in a restricted access area under the custody of the PI. These documents remained at the research site at all times. Participants were provided with a copy of their signed consent form for their records.

Data confidentiality

Current legislation will be complied with in terms of data confidentiality protection (European Regulation 2016/679, of 27 April, on the protection of natural persons with regard to the processing of personal data and the free movement of such data and Organic Law 3/2018, of 5 December, on Personal Data Protection and guarantee of digital rights). For this purpose, when applicable, each participant will receive an alphanumeric identification code in the study that will not include any data allowing personal identification (coded CRD). The Principal Investigator will have an independent list that will allow the connection of the identification codes of the patients participating in the study with their clinical and personal data. This document will be filed in a secure area with restricted access, under the custody of the Principal Investigator and will never leave the centre.

Once the paper CRDs are completed and closed by the Principal Investigator, the data will be transferred to a database.

As in the CRDs, the Database will comply with current legislation in terms of data confidentiality protection (European Regulation 2016/679, of 27 April, on the protection of natural persons about the processing of personal data and the free movement of such data and Organic Law 3/2018, of 5 December, on the Protection of Personal Data and guarantee of digital rights) in which no data allowing personal identification of patients will be included.

Information to subjects and informed consent

Patients will be informed orally and in writing about all information regarding the study. The patient will be provided with a copy of the consent form and the information sheet. The investigator will grant the patient the necessary time to ask questions about the study details. The investigator will keep the original signed informed consent in a secure restricted access area.

Bias minimization measures

To minimize bias, automatic image quality checks (DIQA > 70) are implemented to ensure only adequate data is analyzed. The investigational team will be blind to algorithm's result, avoiding bias in the measuremnt of FFA severity assessment.

Calendar

Recruitment period of 12 months. Total study duration estimated at 24 months. Each patient followed for 12 months.

Monitoring plan

A clinical monitoring plan has been established to oversee the progress of the clinical investigation, ensuring that it is conducted, recorded, and reported in accordance with the protocol, Good Clinical Practice, and the applicable regulatory requirements. The Legit.Health team will meet with the investigators periodically to review the collected data and ensure the collection procedure is carried out correctly.

Subject follow-up procedures

Patients will attend a total of two review visits with the investigator. Follow-up visits will be carried out every 6 months from the inclusion visit.

Completition of the investigation

The database will be considered closed after completing all data management processes and resolving discrepancies. Following this, the statistical analysis and final study report will be executed.

Statistical analysis

Variables will be characterized using frequency distributions for qualitative variables and measures of central tendency and variability (mean, median, standard deviation, interquartile range) for quantitative ones. For the automatic hair counting task, a comparison of the MAPE metric with the respective gold standard will be performed, along with a correlation analysis. For the segmentation task, the F1 Score will be compared with the gold standard.

Procedures

Patients will be recruited in the Dermatology Service of the Hospital Universitario Ramón y Cajal. The Principal Investigator or collaborators will explain the study, obtain informed consent, and assign a study ID. In each consultation, clinical and demographic data, FFA Global Staging Score, SALT III, erythema, shed hairs, and recession patterns will be recorded. Photographs (trichoscopic images of left lateral, right lateral, left medial, right medial, and midline) will be taken every 6 months using specific nomenclature and stored pseudonymously. The dataset will be used to validate the AI algorithms.

Data management

The data will be managed and tabulated with consistency rules and logical ranges to control inconsistencies during data tabulation. A validation process of the clinical data will be carried out by running computer filters based on validation rules, which will automatically identify missing values or inconsistencies of clinical data according to the protocol. Additionally, manual editing and validation will be performed using descriptive and exploratory statistical techniques to complement the detection of logical errors and inconsistent values.

The database will be considered closed upon completion of all data management processes and satisfactory resolution of discrepancies and errors in the data. Any changes in the database after its closure can only be made after written agreement between the Principal Investigator and the technical coordinators of the project.

AI Labs Group, S.L. (hereinafter, the manufacturer) is the owner of the device. During the period of validity of this study, the manufacturer will grant a license to use the device by the research team free of charge. The research team will be the administrator of the account. Both patients and members of the medical team will have login credentials. The manufacturer will not have access to the account or patient information.

According to the definitions and roles set out in Regulation (EU) 2016/679 (GDPR), the Data Controller is the research team and the manufacturer is the Data Processor.

The storage of data and photographs will be in line with the European Regulation 2016/679 (GDPR) and the Organic Law 3/2018 of 5 December on the Protection of Personal Data and guarantee of digital rights. At the end of the study, all information stored in the device will be totally and permanently deleted.

The device complies with current legislation on the protection and confidentiality of personal data European Regulation 2016/679 (GDPR). Appropriate technical and organizational security measures are adopted to ensure the security of personal data and prevent its alteration, loss, unauthorized processing or access, given the state of technology, the nature of the data and the risks to which they are exposed, whether from human action or the natural physical environment.

CIP Modification

As indicated in the UNE-EN ISO 14155:2021 standard, the Clinical Investigation Plan (CIP) may be modified as necessary during the clinical investigation. The changes made must be described, along with their justification, potential impact on clinical performance, efficacy, safety, or other evaluation criteria, and identification of other affected documents.

CIP modifications will be prepared by the sponsor and agreed upon and accepted between the sponsor and the principal investigator. The modifications will be recorded with a justification for each one in the form of an amendment or addendum.

The required regulatory authority (AEMPS) and the Ethics Committee or Institutional Review Board (IRB) will be notified, if necessary. Modifications to the clinical investigation may only be implemented once favourable feedback and the corresponding approval have been obtained.

In accordance with Article 75 of Regulation (EU) 2017/745, substantial modifications to the clinical investigation must be approved by both the Ethics Committee for investigation with medicines (CEIm) and the Competent Authority (AEMPS) prior to their implementation.

• In the case of substantial modifications to authorized clinical investigations, a request must be submitted to the AEMPS and the CEIm.
• For non-substantial modifications to authorized clinical investigations, until the corresponding module is available in the EUDAMED database, the updated documentation will be sent to the AEMPS for inclusion in their file.

CIP Deviations

As indicated in the UNE-EN ISO 14155:2021 standard, the investigator may not deviate from the Clinical Investigation Plan (CIP), except in emergencies (section 4.5.4.b of the standard). In such cases, the investigator may proceed without prior approval from the sponsor and the Ethics Committee to protect the rights, safety, and well-being of human subjects. The use of waivers from the Clinical Investigation Plan is strictly prohibited.

These deviations must be documented by the principal investigator and notified to the sponsor and the IRB as soon as possible, and always within a maximum of 15 days. Immediately after receiving the notification, the sponsor will record and analyze the deviations carried out and their potential impact. Depending on the findings, the sponsor will take the necessary corrective and/or preventive measures.

In other circumstances, when deviations affect the rights, safety, and well-being of the subject or the scientific integrity of the clinical investigation, deviation requests and reports must be provided to the IRB if required.

Start, follow-up and end reports

The start of the study will be notified to the ethics committee.

Upon obtaining the study conclusions, a final report (T-015-006 Clinical Investigation Report (CIR)) will be prepared and submitted to the ethics committee.

Statements of compliance

The present clinical investigation will be conducted following the ethical principles originating from the Declaration of Helsinki.

Additionally, the clinical investigation will comply with the harmonized standard UNE-EN ISO 14155:2021 and the European Regulation MDR 2017/745. The statement specifying compliance with the general safety and performance requirements in accordance with MDR can be found in the document Manufacturer's Declaration of Compliance with Requirements.

As appropiate, clinical investigation will not commence until approval/favourable opinion has been obtained from the Clinical Research Ethics Committee (CREC) and the required regulatory authority (Spanish Agency for Medicines and Medical Devices, AEMPS), and it must comply with any additional requirements imposed by the CREC and/or AEMPS.

The statement regarding the funding of the clinical investigation, along with the description of the agreement between the sponsor and the research centers and between the sponsor and the principal investigator, can be found in the Clinical Trial Agreement (CTA) and can be accessed upon request.

Adverse events, adverse product reactions and product deficiencies

Adverse Events (AE) and Adverse Event to Product (AEP)

An AE is any unintended medical event, unanticipated illness or injury, or unintended clinical signs (including abnormal laboratory findings) in subjects, users, or other persons, whether or not related to the investigational product and whether intended or unintended.

A AEP is an adverse event related to the use of an investigational medical device.

Given these definitions, potential AEPs or AEs are documented in the product's IFU.

Product deficencies

Possible inadequacies of a medical device may relate to its identity, quality, durability, reliability, safety, or performance.

Considering this definition, the following issues could arise:

• Malfunctions, such as application crashes or failure to process images.
• Use errors, such as capturing poor quality photographs or incorrect data entry.
• Inadequate information provided by the manufacturer, such as a complex IFU and/or labeling.

Product deficiencies in the investigation will be managed by the sponsor according to non-conforming product control procedures. When appropriate, corrective and/or preventive actions will be taken to protect the safety of subjects, users, and individuals.

Serious Adverse Events, serios adverse events to product and serious and unexpected adverse event to the product

According to UNE-EN ISO 14155:2021:

• A Serious Adverse Product Reaction (SAEP) is a SAE that has produced any consequence characteristic of a serious adverse event.
• A Serious Adverse Event (SAE) is an AE that resulted in any of the following events: death, serious deterioration of the health status of the subject, users or other persons, or fetal distress, fetal death, congenital anomaly or birth defect.
• A Serious Unexpected Adverse Event to the Product (SUAEP) is a SAE that, due to its nature, incidence, intensity or consequences, has not been identified in the updated risk assessment.

Taking into account these definitions, there are no SAEP, SAEs or SUAEPs related to the use of the product.

Non-reportable Adverse Events

note

List non-reportable adverse events, if applicable, including justification.

There are no specific non-reportable adverse events defined for this study. Since this is an observational study using a digital tool without therapeutic intervention, subjects are not exposed to any procedures that could endanger their safety, and no adverse events related to the investigational product are expected.

Notification Process

Any SAEP, product deficiency or finding related to the above will be duly documented and reported in accordance with the provisions of document MDCG 2020-10/1 “Safety reporting in clinical investigations of medical devices under the Regulation (EU) 2017/745”

In the situations detailed in the previous paragraph, the principal investigator must notify the sponsor immediately (but no later than 3 days after becoming aware of the event). The sponsor will then use the form published as an annex to said document, MDCG 2020-10/2 “Guidance safety report form”.

This form must be completed or updated for each reportable event or for new findings or updates of events already reported. It will be transmitted to all National Competent Authorities (NCA) where the clinical investigation is being conducted. In this case, the AEMPS.

The notification period of the sponsor to the NCA(s) will be immediately (but no later than 2 days after becoming aware of the event) for reportable events that involve an imminent risk of death, serious injury or serious illness and that require immediate corrective action, or new findings or updates of related events. For the rest of reportable events or new findings or updates, the notification period will be immediately (but no later than 7 days after becoming aware of the event).

Likewise, as indicated in the UNE-EN ISO 14155:2021 regulation, the IRB must be notified of the SAEs, if the IRB so requires.

Foreseeable adverse events and adverse events to product

The foreseeable adverse events and expected adverse reactions to the product, as well as their incidence, mitigation and treatment are documented in the T-013-002 Risk management record of the product under study.

Emergency contact

The emergency contact person for reporting serious adverse events and serious adverse effects of the product:

• Name: Dr. Daniel Ortega Quijano
• Professional role: Principal Investigator
• E-mail: daniel-oq@hotmail.com

Data Monitoring Committee (DMC)

Information on the DMC (Data Monitoring Committee), if established. This is an independent committee that the sponsor may establish to evaluate, at indicated intervals, the progress of the clinical investigation, the safety data or the critical clinical performance or efficacy endpoints and to recommend to the sponsor whether to continue, suspend, modify, or stop the clinical investigation.

Vulnerable population (if applicable)

N/A

Suspension or early termination of clinical research

As indicated in the UNE-EN ISO 14155:2021 regulation, the sponsor may suspend or terminate the clinical research early for significant and documented reasons. These are:

• If during the clinical research the suspicion of an unacceptable risk arises, including a serious threat to the health of the subjects. It must be suspended while the risk is determined.
• If an unacceptable risk that cannot be controlled is confirmed.
• Due to the impossibility of including a minimum number of subjects that allows the final assessment of the study within a reasonable period according to the characteristics of the study.
• When instructed by the IRB or the required regulatory authority (AEMPS).
• Due to non-compliance with the obligations assumed in the contract by any of the contracting parties.
• By mutual agreement between the parties, expressed in writing.
• By the will of one of the parties, expressed in writing at least one month in advance.

In the event of a suspension or early termination of the clinical research, the sponsor will inform the AEMPS. The sponsor must provide the resources to comply with the obligations of the CIP and with the existing agreements. The principal investigator must inform the subjects if so stipulated in the agreement between the sponsor and the research centre.

If the clinical investigation is resumed, the sponsor must inform the principal investigator and, where appropriate, the AEMPS. Approval from the IRB and, where appropriate, from the AEMPS will be required for such resumption. The principal investigator must inform the subjects.

In accordance with Article 77 of Regulation (EU) 2017/745, the sponsor must notify the Member States in which the clinical investigation is being conducted of the end of the clinical investigation, its temporary halt, or its early termination, within the deadlines specified by the regulation (within 15 days of the end, or within 24 hours in case of early termination or temporary halt for safety reasons). This notification must be accompanied by a justification in case of early termination or temporary halt.

Publication policy

Statement indicating the conditions and time periods in which the results of the clinical research will be offered for publication, including the role played by the sponsor and the criteria for authorship of the publication.

The description of the clinical research will be recorded in a publicly accessible database before the recruitment of the first subject. Its content will be updated during the conduct of the clinical research.

In accordance with the legal requirements and ethical principles established in Section 1 of Chapter I of Annex XV of Regulation (EU) 2017/745, a Clinical Investigation Report (T-015-006 Clinical Investigation Report (CIR)) will be prepared within one year of the end of the clinical investigation or within three months of its early termination or temporary halt. The CIR will be provided to the IRB and the AEMPS.

The results of the clinical investigation will be published in the aforementioned public database. The summary of the clinical investigation report and its results (whether positive, negative, or inconclusive) will be made available to the public within 1 year from the end of the clinical investigation, or within 3 months in the event of early termination or temporary halt.

In addition, if deemed appropriate, the results obtained will be published in scientific journals. The CEIC that has approved this clinical research will be mentioned, and the funds obtained by the author for or for its conduct and the source of funding will be stated. The anonymity of the subjects participating in the clinical research will be maintained at all times.

After the completion of the study, the results of the clinical utility and satisfaction surveys carried out according to the model in Annex I may be communicated at congresses and scientific meetings with prior authorization from both parties. Communications and press releases may also be made to communicate the results of the study. All publications and communications must be accepted and approved by the parties involved.

Bibliography

References can be consulted in the original PDF protocol document.

Signature meaning

The signatures for the approval process of this document can be found in the verified commits at the repository for the QMS. As a reference, the team members who are expected to participate in this document and their roles in the approval process, as defined in Annex I Responsibility Matrix of the GP-001, are:

• Author: Team members involved
• Reviewer: JD-003 Design & Development Manager, JD-004 Quality Manager & PRRC
• Approver: JD-001 General Manager

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