Efficacy and Safety Evaluation of Nerandomilast in Systemic Autoimmune Rheumatic Diseases-Associated Interstitial Lung Diseases: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this study is to evaluate the effect of **nerandomilast** on the extent of pulmonary involvement in patients with Systemic Autoimmune Rheumatic Diseases associated Interstitial Lung Diseases (SARD-ILD) over a 26-week period. This will be assessed using the quantitative interstitial lung disease (QILD) score derived from quantitative high-resolution computed tomography (qHRCT). The clinical relevance of this objective lies in its potential to provide insights into the efficacy of nerandomilast in reducing lung involvement, which is a critical aspect of managing SARD-ILD.

Secondary objectives include exploring the efficacy of nerandomilast based on additional qHRCT parameters, assessing changes in lung function via forced vital capacity (FVC), and evaluating its effect on patient-reported symptoms of dyspnoea and cough. Additionally, the study will focus on the safety profile of nerandomilast by examining the risk of infections through the occurrence of infection-related adverse events (AEs). These secondary objectives aim to provide a comprehensive understanding of both the therapeutic benefits and safety of nerandomilast in this patient population.

The clinical trial involves a total of **242 participants** diagnosed with **Systemic Autoimmune Rheumatic Diseases associated Interstitial Lung Diseases (SARD-ILD)**. The study population includes both male and female subjects, with an age range encompassing adults and older adults. Participants were selected based on specific inclusion criteria, including a confirmed diagnosis of SARD-ILD by a rheumatologist and the presence of fibrotic interstitial lung disease on high-resolution computed tomography. The trial does not involve a vulnerable population. Participants are required to have stable treatment with immunosuppressive agents or nintedanib, with no planned changes in their background standard of care treatment. The selection process ensures that participants have not shown significant lung function improvement or clinically significant improvement in interstitial lung disease as a response to prior therapy. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria.

The clinical trial is designed to evaluate the efficacy and safety of **nerandomilast** in patients with **Systemic Autoimmune Rheumatic Diseases associated Interstitial Lung Diseases (SARD-ILD)**. This study is a randomized, double-blind, placebo-controlled trial with a duration of 26 weeks. Participants will be randomly assigned to receive either the active treatment, **BI 1015550**, or a placebo, both administered as film-coated tablets for oral use. The primary objective is to assess the effect of the treatment on pulmonary involvement, measured by the quantitative interstitial lung disease (QILD) score using quantitative high-resolution computed tomography (qHRCT) from baseline to Week 26.

The trial will commence with an inclusion (screening) visit to determine eligibility based on specific criteria, such as the presence of fibrotic interstitial lung disease (ILD) and stable treatment with immunosuppressive agents. Following successful screening, participants will undergo baseline assessments before randomization. Study visits will occur at regular intervals to monitor safety, efficacy, and any adverse events. These visits will include assessments of lung function, imaging, and symptom evaluation. The end-of-study visit will occur at Week 26, where final evaluations will be conducted to assess the primary and secondary endpoints, including changes in lung fibrosis and ground glass opacity scores, as well as functional and symptomatic outcomes.

Participant involvement is expected to last for the entire 26-week duration of the trial. However, early termination may occur if participants experience significant adverse events, fail to adhere to the study protocol, or if the investigator deems it necessary for the participant's safety. The trial aims to provide comprehensive data on the potential benefits and risks of **nerandomilast** in this patient population, contributing to the understanding of its role in managing SARD-ILD.

The clinical trial involves the administration of **BI 1015550**, an experimental medication formulated as a **film-coated tablet**. The active substance in BI 1015550 is **1-[[(5R)-2-[4-(5-chloro-2-pyrimidinyl)-1-piperidinyl]-6,7-dihydro-5-oxidothieno[3,2-d]pyrimidin-4-yl]amino]-cyclobutanemethanol**, which is of chemical origin. The medication is intended for **oral use**. The trial is designed to evaluate the efficacy and safety of BI 1015550 over a period of 26 weeks in patients with Systemic Autoimmune Rheumatic Diseases associated Interstitial Lung Diseases (SARD-ILD). The dosing schedule and specific dosage amounts are not explicitly detailed in the provided data, but the maximum treatment period is specified as 26 weeks.

In addition to the experimental medication, a **placebo** is used as a comparator treatment in this double-blind, randomized, placebo-controlled trial. The placebo is designed to match the appearance of the nerandomilast (BI 1015550) film-coated tablet, ensuring blinding of both participants and investigators. The placebo does not contain any active pharmaceutical ingredients and serves as a control to assess the true efficacy and safety of the experimental treatment. The administration route and frequency for the placebo are intended to mirror those of the experimental medication, although specific details are not provided in the data.

The efficacy of nerandomilast in patients with Systemic Autoimmune Rheumatic Diseases associated **Interstitial Lung Diseases** (SARD-ILD) will be assessed through a double-blind, randomized, placebo-controlled trial over a period of 26 weeks. The primary endpoint for evaluating efficacy is the absolute change from baseline in the quantitative interstitial lung disease (QILD) score at Week 26, as measured by quantitative high-resolution computed tomography (qHRCT). This primary endpoint will provide insights into the extent of pulmonary involvement and the effect of the treatment.

Secondary endpoints include the absolute change from baseline in quantitative lung fibrosis (QLF) score, quantitative ground glass opacity (QGGO) score, and forced vital capacity (FVC) in milliliters at Week 26. Additionally, patient-reported outcomes will be assessed through changes in the Living with Pulmonary Fibrosis (L-PF) Symptoms Dyspnoea and Cough domain scores at Week 26. The occurrence of infection-related adverse events from baseline to Week 26 will also be monitored as part of the secondary efficacy assessments.