Study of BI 1015550 and nerandomilast to assess safety, dosing and efficacy in children and adolescents with fibrosing interstitial lung disease

Primary objective: characterize the dose‑exposure relationship and evaluate the safety of nerandomilast in children and adolescents (2 – < 18 years) with fibrosing interstitial lung disease, generating data to inform age‑appropriate dosing. Secondary objectives: • continued assessment of safety parameters during treatment; • investigation of exploratory efficacy outcomes, such as changes in lung function, symptom scores, and disease‑related biomarkers; • collection of pharmacokinetic data to support the dose‑exposure analysis.

Twenty‑one participants were enrolled, comprising both female and male children and adolescents aged 2 years up to but not including 18 years. All subjects had a confirmed diagnosis of fibrosing interstitial lung disease based on high‑resolution computed tomography performed within 12 months prior to screening and central radiologic review. Eligibility required evidence of clinically significant disease, such as a Fan score ≥ 3 or documented progression indicated by relative declines in forced vital capacity % predicted, worsening symptoms, increased fibrosis on imaging, or heightened oxygen requirement. For participants aged ≥6 years, a forced vital capacity ≥25 % of predicted was required. Subjects were selected from the patient population meeting these criteria, with no additional lifestyle restrictions reported. The cohort included vulnerable participants as defined by age, and all were otherwise in a health status consistent with the presence of progressive fibrosing lung disease.

The trial is a phase‑5 study evaluating the dose‑exposure, safety, and exploratory efficacy of nerandomilast in children and adolescents with fibrosing interstitial lung disease. Part A uses a randomized, double‑blind, placebo‑controlled design for participants aged 6 to < 18 years, while children aged 2 to < 6 years receive open‑label active treatment. After Part A, all subjects enter Part B, an open‑label extension with active drug. Participant involvement lasts up to 52 weeks. The visit schedule includes a screening visit to confirm eligibility, a baseline/randomization visit to start study medication, and follow‑up visits at Week 2, Week 26, Week 28 (pharmacokinetic sampling in Part B), and Week 52 (end‑of‑study). Safety assessments continue after the final visit. Primary endpoints comprise steady‑state pharmacokinetic exposure and occurrence of treatment‑emergent adverse events through Week 26; secondary endpoints assess changes in oxygen saturation, growth, quality of life, lung function, and time‑to‑event outcomes. Early termination may occur for medically significant adverse events, lack of protocol compliance, withdrawal of consent, or investigator decision based on safety concerns.

The investigational agent BI 1015550 is supplied as a film‑coated tablet for oral use. Each tablet contains 0 mg of the active substance (as specified in the protocol) and is administered orally; the specific dosing schedule is defined by the study protocol for each age cohort.

The second investigational product, nerandomilast, is also provided as a film‑coated tablet intended for oral administration. The tablet contains 0 mg of the active ingredient according to the study labeling, with dosing determined by the protocol for participants aged 2 years to less than 18 years.

A matching placebo tablet, containing no active pharmaceutical ingredient, is used as a comparator in the double‑blind portion of the study. The placebo is identical in appearance to the active tablets and is administered orally under the same conditions as the active treatments.

The trial enrolls children and adolescents with fibrosing interstitial lung disease. Participants aged 6 years to less than 18 years receive either the active tablet or placebo in a double‑blind, placebo‑controlled design (Part A). Children aged 2 years to less than 6 years receive open‑label active treatment during Part A, followed by an open‑label extension (Part B) in which all participants receive active therapy.

Efficacy will be evaluated using a set of secondary endpoints that quantify functional, physiological, and patient‑reported outcomes. The primary efficacy parameters include the absolute change from baseline in oxygen saturation (SpO₂) [%] on room air at rest measured at Week 26 and Week 52, the absolute change from baseline in forced vital capacity (FVC) [% predicted] at the same time points for participants aged ≥ 6 years, and the absolute change from baseline in 6‑minute walk distance (m) at Week 26 and Week 52 for participants aged ≥ 6 years. Additional efficacy measures comprise the absolute change from baseline in height (cm) and in the Pediatric Quality of Life Inventory™ (PedsQL™) score, both assessed at Week 26 and Week 52.

These parameters will be collected using validated clinical tools: SpO₂ will be obtained with a pulse oximeter on room air while the participant is at rest; FVC will be measured by standard spirometry in accordance with accepted guidelines; the 6‑minute walk test will be performed on a flat, straight course with standardized instructions; height will be recorded with a calibrated stadiometer; and the PedsQL™ questionnaire will be administered as a patient‑reported outcome instrument. Acceptability of the oral formulation will be assessed by recording the number/size of tablets and the use of the dispenser at Week 2 and Week 26.

Time‑to‑event analyses will also contribute to efficacy assessment. The trial will capture the time from randomisation to the first respiratory‑related hospitalisation, the time to the first acute interstitial lung disease (ILD) exacerbation or death, and overall time to death, with events monitored continuously throughout the study period.