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	Validación clínica de un algoritmo de inteligencia artificial para el cálculo automático de la gravedad y evolución de heridas crónicas / Clinical validation of an artificial intelligence algorithm for the automatic calculation of the severity and evolution of chronic wounds
Device under investigation	Legit.Health Plus
Protocol version	Version 1.0
Date	23/01/2026
Protocol code	Legit.Health_DAO_wounds
Sponsor	AI LABS GROUP, S.L (Legit.Health)
Coordinating Investigator	Jose Francisco Villalba Salazar
Principal Investigator(s)	Jose Francisco Villalba Salazar
Collaborating Investigator(s)	Jose Luis Coves, Miriam López Nicolás, Ovidia López Pérez, Patricia rodenas García, Lidia Aibar Rubio, Alfonso Medela, Andy Aguilar, Taig Mac Carthy, Jordi Barrachina
Investigational site(s)	Vinalopó University Hospital, Toscar Health Centre
Ethics Committee	Comité Ético de Investigación con medicamentos (CEIm) del Hospital Universitario del Vinalopó

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

Jose Francisco Villalba Salazar Vinalopó Health Department Vinalopó University Hospital Tonico Sansano Mora Street, 14, 03293 Elche (Alicante)

Coordinating Investigator(s)

Jose Francisco Villalba Salazar

Collaborating Investigator(s)

• Jose Luis Coves (Vinalopó Health Department)
• Miriam López Nicolás (Vinalopó Health Department)
• Ovidia López Pérez (Vinalopó Health Department)
• Patricia rodenas García (Vinalopó Health Department)
• Lidia Aibar Rubio (Vinalopó Health Department)
• Alfonso Medela (AI LABS GROUP SL)
• Andy Aguilar (AI LABS GROUP SL)
• Taig Mac Carthy (AI LABS GROUP SL)
• Jordi Barrachina (AI LABS GROUP SL)

Investigational sites

• Vinalopó University Hospital. Calle Tonico Sansano Mora, 14, 03293 Elche (Alicante)
• Toscar Health Centre. Calle Vicente Fuentes Sansano 36, 03205 Elche (Alicante)

Funding

Sponsor: AI LABS GROUP, S.L. No external funding sources are anticipated. The associated costs of project execution are privately managed.

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 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

Pressure ulcers (PU), also known as bedsores, are localized areas of tissue damage resulting from sustained pressure or friction on the skin and underlying tissues. They represent a significant burden on healthcare systems, affecting patients' quality of life and increasing treatment costs. In Spain, up to 13% of nursing consultations are estimated to be caused by pressure ulcers.

Traditionally, wound evaluation relies on manual visual analysis to assess characteristics like size, developmental stage, and tissue composition. However, this is subjective, time-consuming, and prone to inconsistencies. To improve precision and consistency, AI-powered Computer-Aided Diagnosis (CADx) systems are increasingly integrated into clinical workflows. These systems provide automated segmentation, classification, and severity assessment of wounds.

Legit.Health has developed the AWOSI (Automatic WOund Severity Index) system, a CADx designed to support clinicians using advanced deep learning methods. It includes models that segment tissue types such as erythema, granulation tissue, slough, necrotic tissue, macerated areas, orthopedic materials, and bone. It calculates an automated severity score aligned with the RESVECH index, identifying 23 specific visual signs.

Evaluation of preclinical and clinical data

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

Hypothesis

The central hypothesis posits that the Legit.Health AWOSI system is capable of automatically evaluating wound severity with an accuracy similar to the current reference standard, represented by an expert healthcare professional using the WOSI (Wound Severity Index) scale on paper. This involves accurately identifying affected areas, standardizing measurements independently of the observer, determining extension, and assessing severity based on image patterns.

Objectives

Primary objetive(s)

Develop and validate an automatic wound severity measurement system (AWOSI) based on artificial intelligence, aiming to evaluate the severity of various types of wounds accurately, efficiently, and standardized in a hospital environment, equaling or surpassing the precision of the current "gold standard" (a professional using the WOSI tool on paper).

Secondary objective(s)

• Validate that using the AWOSI system significantly reduces the time needed to evaluate wound severity compared to the conventional paper-based WOSI method.
• Validate if the AWOSI system offers comparable or superior accuracy and performance to WOSI evaluated by a clinical expert.
• Determine the perceived clinical utility and degree of satisfaction of healthcare professionals using AWOSI.
• Determine the perceived degree of usability (SUS) of the AWOSI system.

Summary of the study

This is an observational, prospective, and cross-sectional study. The target population consists of adult patients (≥ 18 years) with different types of wounds (chronic wounds, pressure ulcers or burns, traumatic, vascular, or surgical tumors) treated at the El Toscar health center. The study includes a maximum of 6 nurses, each attending 4-5 patients (maximum 30 patients in total). The study duration is 1 month, including a 2-week recruitment period and 2 weeks for analysis.

Design and Methods

Type of clinical research

Observational, prospective, and cross-sectional study.

Population

Adult patients (≥ 18 years) with different types of wounds treated at the El Toscar health center by the participating investigators.

Duration

Recruitment period: 2 weeks. Total study duration: 1 month (including recruitment, database closure, and analysis).

Acceptance criteria

• AWOSI measurements present a Mean Squared Error (MSE) and correlation that is comparable or superior to the expert WOSI measurements.
• Statistically significant reduction in the time needed to assess a wound with AWOSI compared to WOSI on paper (p < 0.05).
• High usability and satisfaction scores measured by the CUS and SUS scales.

Inclusion and exclusion criteria

Inclusion Criteria:

• Patients with wounds being treated at the El Toscar health center.
• Patients aged 18 years or older.

Exclusion Criteria:

• Patients under 18 years of age.

Variables

Primary Variable:

• Severity of chronic wounds or ulcers, measured by:
  1. The reference standard WOSI, used by a specialist in paper format.
  2. The AWOSI system of the Legit.Health medical device.

Secondary Variables:

• Demographic data: sex and age.
• Measurement time: Duration of the ulcer severity evaluation process using WOSI and the AWOSI system.
• Accuracy in severity: Comparison of precision between the WOSI system and the AWOSI system against the gold standard (an expert in ulcer evaluation).
• Annotations of the visible signs of the WOSI questionnaire.
• Clinical Utility and Satisfaction (CUS) degree of the healthcare professional.
• System Usability Scale (SUS).

Condition of interest

Evaluation of the severity and evolution of chronic wounds using an AI automatic calculation algorithm.

Quality control

The Principal Investigator will review and approve the protocol, ensure confidentiality, and oversee 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

Limitations include the quantity and quality of collected images. Variability in illumination, color, shape, size, and focus are determinant. Inadequate delimitation of the lesion in the photograph could confuse the algorithm. The "Hawthorne effect" may also be present, where observers might change their judgments knowing they are being evaluated.

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 or their legal representatives must provide written consent before inclusion in the study after fully understanding the objectives, risks, benefits, and conditions. They will be informed objectively in a non-technical language. Every signed consent will be kept securely by the research team, and a copy will be provided to the subject.

Bias minimization measures

To minimize bias from the investigator evaluating the image with Legit.Health, the principal investigator (gold standard) will take a different photograph with a corporate smartphone for the expert evaluation, preventing conditioning from the collaborating investigator's prior actions.

Calendar

Recruitment: 2 weeks. Total duration: 1 month.

Monitoring plan

Legit.Health will conduct a training session with the investigators prior to the study. Legit.Health will also oversee the correct execution of the protocol and ensure proper data collection, offering technical support throughout the study.

Subject follow-up procedures

Cross-sectional nature; patients are recruited and evaluated during their routine visit for wound treatment. Their standard wound care will not be altered.

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, SD, IQR) for quantitative variables. To validate the AWOSI system, the Mean Squared Error (MSE) will be calculated between the gold standard and the AWOSI model. A Pearson or Spearman correlation analysis will be performed depending on the distribution. T-Student or Mann-Whitney tests will evaluate the reduction in measurement time. Significance will be set at p < 0.05.

Procedures

Nurses will evaluate the wound using the paper WOSI, timing the process. They will then take a photograph and process it with Legit.Health's AWOSI, also timing this process. Later, an expert will take a separate photograph and evaluate the wound using the paper WOSI (acting as the gold standard). The results, times, and visible signs will be entered into the electronic CRD. Upon study completion, investigators will fill out the CUS and SUS questionnaires.

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: Jose Francisco Villalba Salazar
• Professional role: Principal Investigator
• E-mail: jfvillalba@vinaloposalud.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

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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