Long-term Safety and Efficacy Evaluation of Oral BI 1015550 in Patients with Idiopathic and Progressive Pulmonary Fibrosis

The primary objective of this study is to assess the long-term **tolerability**, safety, and efficacy of oral nerandomilast treatment in patients with **idiopathic pulmonary fibrosis** (IPF) and other types of **progressive pulmonary fibrosis** (PPF) who have completed planned treatment in the pivotal Phase III parent trials. The primary focus is to descriptively assess the incidence of patients experiencing any adverse event while on treatment. This is clinically relevant as it provides insights into the long-term safety profile of nerandomilast, which is crucial for managing chronic conditions like IPF and PPF.

Secondary objectives include a descriptive assessment of the efficacy of nerandomilast treatment. This evaluation is important to understand the potential benefits of the treatment in improving patient outcomes over an extended period.

The clinical trial involves a total of **1307 participants** who have been diagnosed with **idiopathic pulmonary fibrosis (IPF)** or other types of **progressive pulmonary fibrosis (PPF)**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on their completion of treatment in the parent trials (1305-0014 or 1305-0023) without prematurely discontinuing treatment permanently. The trial includes a vulnerable population, indicating that special considerations are in place for their participation. Participants are required to have signed and dated written informed consent in accordance with ICH-GCP and local legislation. Women of childbearing potential must adhere to strict birth control measures to ensure safety during the trial. The study does not specify particular lifestyle considerations such as diet or physical activity, focusing instead on the long-term tolerability, safety, and efficacy of oral nerandomilast treatment in the specified patient population.

The clinical trial is designed to evaluate the long-term tolerability, safety, and efficacy of **nerandomilast** in patients with **idiopathic pulmonary fibrosis** (IPF) and **progressive pulmonary fibrosis** (PPF) who have completed treatment in previous Phase III trials. This open-label extension trial will not involve treatment comparisons and will focus on the incidence of adverse events while on treatment. The trial is expected to commence recruitment on September 26, 2024, and conclude by May 5, 2027, with a total duration of approximately 99 weeks for each participant.

Participants will be required to attend several study visits throughout the trial. The initial visit will serve as a screening to confirm eligibility, ensuring that participants have completed the parent trials without prematurely discontinuing treatment. Subsequent visits will be scheduled to monitor the participants' health status, assess the primary endpoint of adverse events, and evaluate secondary endpoints such as changes in forced vital capacity (FVC) and time to exacerbation or hospitalization. The end-of-study visit will occur at week 99, marking the completion of the trial for each participant.

Participant involvement is expected to last for the entire duration of the trial, approximately 99 weeks, unless early termination is warranted. Conditions that may lead to early termination include the occurrence of significant adverse events, withdrawal of consent, or any protocol deviations that compromise the integrity of the trial. The trial will adhere to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines and local regulations, ensuring the safety and well-being of all participants.

The clinical trial involves the administration of the experimental medication **BI 1015550**, which is provided in the form of a **film-coated tablet**. The active substance in this medication is **1-[[(5R)-2-[4-(5-chloro-2-pyrimidinyl)-1-piperidinyl]-6,7-dihydro-5-oxidothieno[3,2-d]pyrimidin-4-yl]amino]-cyclobutanemethanol**, a chemical compound developed by Boehringer Ingelheim International. The medication is administered orally, with a maximum daily dose of 18 mg, and a total maximum dose of 13,140 mg over a treatment period of 98 days. The medication is not formulated for pediatric use and is not classified as an orphan drug.

Another formulation of **BI 1015550** is also utilized in the trial, similarly provided as a **film-coated tablet**. This formulation contains the active substance **BI 1015550**, also of chemical origin, and is administered orally. The maximum daily dose for this formulation is 36 mg, with a total maximum dose of 26,280 mg over the same 98-day treatment period. This formulation is likewise not intended for pediatric use and is not designated as an orphan drug.

Both formulations of **BI 1015550** are used to assess the long-term safety and efficacy in patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF). The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen.

The efficacy of the clinical trial will be assessed through a series of predefined endpoints. The primary endpoint is the incidence of any adverse event over the course of the extension trial, which will be monitored up until the follow-up or end-of-study visit planned at week 99. Secondary endpoints include the absolute change from baseline in Forced Vital Capacity (FVC) measured in milliliters and as a percentage of predicted FVC over time. Additionally, the time to an absolute decline in FVC % predicted of greater than 10% from baseline, time to first acute exacerbation of **idiopathic pulmonary fibrosis (IPF)** or progressive pulmonary fibrosis (PPF), first hospitalization for a respiratory cause, or death will be evaluated. Other secondary endpoints involve the time to hospitalization for respiratory causes or death, and the time to a relative decline in FVC % predicted of greater than 10% from baseline or death over the duration of the trial.