Evaluation of Allogeneic Wharton's Jelly-Derived Mesenchymal Stem Cells, Pirfenidone, and Nintedanib in Fibrotic Interstitial Lung Disease Treatment

The primary objective of this study is to evaluate the **safety** and potential therapeutic efficacy of allogeneic mesenchymal stem cells derived from Wharton's jelly in the treatment of fibrotic interstitial lung diseases, with a particular focus on idiopathic pulmonary fibrosis and pulmonary fibrosis following COVID-19. This is clinically relevant as these conditions are characterized by progressive lung scarring, leading to significant morbidity and mortality, and current treatment options are limited.

Secondary objectives include the assessment of: - Changes in forced vital capacity (FVC), which is a critical measure of lung function. - Quality of life of patients, providing insight into the broader impact of the treatment on daily living. - Number of exacerbations during the annual follow-up, which can indicate the treatment's effect on disease stability. - Survival during the annual follow-up, offering data on the potential life-extending benefits of the treatment. - Pharmacokinetics and pharmacodynamics of the mesenchymal stem cell preparation post-administration, which are essential for understanding the drug's behavior in the body and its mechanism of action.

The clinical trial focuses on evaluating the usage and safety of allogenic Mesenchymal cells of Wharton Jelly as a potential treatment for **fibrotic interstitial lung disease**, including idiopathic pulmonary fibrosis and pulmonary fibrosis following COVID-19. The study population comprises both male and female participants over the age of 18, with no vulnerable populations included. Participants are divided into two groups: those diagnosed with idiopathic pulmonary fibrosis and those with restrictive fibrosis post-COVID-19. The trial does not specify the total number of participants, as the sponsor has not provided this information. Participants were selected based on specific criteria, including a confirmed diagnosis of interstitial lung fibrosis and, for the post-COVID-19 group, a history of severe COVID-19 pneumonia with a negative SARS-COV2 antigenic test at least four weeks prior to inclusion. The study does not emphasize any particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the **safety** and efficacy of allogeneic Wharton's jelly-derived mesenchymal stem cells (WJMSCs) in the treatment of **fibrotic interstitial lung disease**, including idiopathic pulmonary fibrosis and pulmonary fibrosis following COVID-19. This trial is structured as a randomized, double-blind, controlled study, integrating Phase I and Phase IIa components. The trial is expected to span from January 2022 to March 2025, with participant involvement lasting approximately one year. The study will include multiple visits: an initial screening visit, regular follow-up visits, and a final end-of-study visit.

During the screening visit, eligibility criteria will be assessed, including age, diagnosis, and lung function parameters. Participants will be randomly assigned to receive either the investigational product, WJMSCs, or a comparator. Follow-up visits will occur at regular intervals to monitor the number and severity of adverse events, changes in forced vital capacity (FVC), quality of life, and survival rates. The primary endpoints include the assessment of adverse events and the inhibition of FVC decline. Secondary endpoints focus on pharmacokinetics, pharmacodynamics, and overall survival.

Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with study procedures, or withdraw consent. The trial aims to provide comprehensive data on the potential of WJMSCs as a therapeutic option for fibrotic interstitial lung diseases, contributing to the understanding of their role in managing these conditions.

The clinical trial involves the administration of several treatments, including **pirfenidone**, which is marketed under the name Esbriet. This medication is provided in the form of 267 mg **film-coated tablets**. The route of administration is **oral**, and the frequency of administration is determined according to the study protocol. Pirfenidone is a chemical substance and is used as a comparator in the trial. Participant compliance with the dosing schedule will be monitored throughout the study.

Another treatment used in the trial is **allogeneic Wharton's jelly-derived mesenchymal stem cells**. This investigational product is provided as a **suspension for injection**. The route of administration is via **injection**, and it is classified as an advanced therapy investigational medicinal product, specifically a somatic cell therapy medicinal product. This treatment is the primary test substance in the study, and its administration schedule is outlined in the trial protocol. Compliance with the administration schedule will be closely monitored.

The trial also includes the use of **nintedanib**, marketed as Ofev, which is provided in the form of 100 mg **soft capsules**. The route of administration is **oral**, and it serves as a comparator in the study. The dosing schedule is specified in the study protocol, and participant adherence to the regimen will be assessed regularly.

A placebo is also utilized in the trial, consisting of a solution of 10% dimethylsulfoxide in 5% human albumin. This solution does not have a specified pharmaceutical form or route of administration in the provided data. The placebo is used to ensure the validity of the trial results by providing a control for comparison with the active treatments. Compliance with placebo administration will be monitored as part of the study procedures.

The clinical trial aims to assess the efficacy of **allogeneic Wharton's jelly-derived mesenchymal stem cells** in the treatment of fibrotic interstitial lung diseases, including idiopathic pulmonary fibrosis and pulmonary fibrosis following COVID-19. Efficacy will be evaluated using both primary and secondary endpoints. The primary endpoints include the number and severity of adverse events in the treated group compared to the control/placebo group, inhibition of the decline in forced vital capacity (FVC) with a reduction of less than 10% over the course of the study, improvement in quality of life, and annual survival rates.

Secondary endpoints will focus on evaluating changes in FVC, quality of life, the number of exacerbations during the annual follow-up, overall survival during the annual follow-up, and the pharmacokinetics and pharmacodynamics of the mesenchymal stem cell preparation after administration. These parameters will be measured and collected at specified intervals throughout the trial to ensure comprehensive data analysis. The trial is designed as a Phase I and Phase IIa integrated clinical trial, with an estimated end date of March 23, 2025.