Evaluation of BI 765423 on Lung Function in Idiopathic Pulmonary Fibrosis: A Phase IIa Randomized, Double-Blind, Placebo-Controlled Study

Trial ID: 2025-520658-12-00
Protocol: 1493-0002
Sponsor: Boehringer Ingelheim International GmbH

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Diseases & Conditions

Idiopathic pulmonary fibrosis

Objectives

The primary objective of this study is to estimate the absolute difference in means of forced vital capacity (FVC) change from baseline after 12 weeks between BI 765423 and placebo in patients with idiopathic pulmonary fibrosis. This evaluation is intended to assess the efficacy (5) of the investigational product on lung function. The secondary objective includes:

Estimation of the absolute difference in means of log10-transformed surfactant protein D (SP-D) plasma concentration change from baseline after 12 weeks.

The study also evaluates safety (4), tolerability (13), pharmacokinetics (6), and pharmacodynamics (7).

Participants

This clinical trial involves 52 participants diagnosed with idiopathic pulmonary fibrosis. The study population consists of male and female patients within specific age cohorts. Inclusion requires a documented diagnosis confirmed by clinical guidelines or histopathology, alongside an high-resolution computed tomography pattern of usual interstitial pneumonia. Eligible individuals must demonstrate an extent of fibrosis of at least 20% and a forced vital capacity of at least 45% predicted. Additionally, haemoglobin-corrected diffusing capacity of the lungs for carbon monoxide must be at least 20% predicted at the time of baseline assessment.

Plans and Procedures

This Phase IIa, randomised, double-blind, placebo-controlled, parallel group trial is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of BI 765423 in patients diagnosed with idiopathic pulmonary fibrosis. The investigational product is administered via intravenous use as a solution for infusion, either with or without standard of care. The primary objective is to estimate the absolute difference in means of forced vital capacity (FVC) change from baseline after 12 weeks between the test group and the placebo group. Study procedures begin with a screening visit to confirm eligibility through criteria such as age, high-resolution computed tomography (HRCT) findings, and pulmonary function measurements. Following screening, participants undergo treatment to assess changes in FVC, diffusing capacity of the lungs for carbon monoxide (DLCO), and other secondary endpoints over a 12-week period. The trial includes various follow-up assessments to monitor clinical outcomes and safety. The total duration of participant involvement is dictated by the 12-week treatment period and subsequent clinical monitoring.

Treatment

The experimental medication consists of BI 765423, which is provided as a solution for infusion. This substance is administered via intravenous use.

The control group receives a placebo intended to match BI 765423. This study is conducted in patients with idiopathic pulmonary fibrosis and may involve administration alongside standard of care therapy.

Efficacy

The efficacy of BI 765423 in patients with idiopathic pulmonary fibrosis is evaluated using several parameters. The primary endpoint is the absolute change from baseline in forced vital capacity (FVC) measured in milliliters at 12 weeks. Secondary endpoints include the absolute change from baseline in log10-transformed SP-D plasma concentration, the absolute change in distance walked during the 6 meter walking test (6MWT), and the absolute change from baseline in FVC % predicted at 12 weeks.

Additional efficacy assessments at the 12-week timepoint involve:

Absolute change from baseline in DLCO % predicted.
Absolute change from baseline in oxygen saturation (SpO2) on room air at rest.

Inclusion and Exclusion Criteria

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Inclusion Criteria

40 years of age or older at the time of informed consent signature.
Signed and dated written informed consent in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
"Male or female patients. Male patients must not donate sperm while taking part in this study and for a specific period after the last dose of the IMP. Male patients with Woman of childbearing potential (WOCBP) sexual partners must use contraception (male condom) to avoid exposure via seminal fluid during treatment for a specific period after last drug intake. Women can only be included if they are of non-childbearing potential, defined as meeting at least one of the below conditions: • Permanently surgically sterilised (hysterectomy, bilateral salpingectomy and/or bilateral oophorectomy) • Postmenopausal, defined as no menses for 12 months without an alternative medical cause. In questionable cases wherein the menopausal status is uncertain and cannot be clearly determined, the following should be taken into consideration by the investigator: o Women not using sex hormone medication such as hormone replacement therapy may be included if a blood sample confirms levels of follicle stimulating hormone (FSH) > 40 U/L and estradiol < 30 ng/L"
Patients with a documented diagnosis of IPF prior to Visit 1, confirmed by the investigator as per the 2022 American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) Guideline and, if available, surgical lung biopsy or transbronchial lung cryobiopsy histopathology report.
"Patients with an high-resolution computed tomography (HRCT) taken within 12 months of Visit 1 (or during the screening period, if not available) confirming “UIP” or “probable UIP” HRCT pattern consistent with the clinical diagnosis of IPF by central review (prior to Visit 2). • Patients with an “indeterminate” HRCT finding are eligible if a clinical diagnosis of IPF can be confirmed based on an historical histopathology report of a surgical lung biopsy or cryobiopsy demonstrating a “UIP” or “Probable UIP” pattern or Multidisciplinary Discussion and Diagnosis as per ATS guidelines. • Patients with an “alternative diagnosis” HRCT finding are eligible if a clinical diagnosis of IPF can be confirmed based on an historical histopathology report of a surgical lung biopsy or cryobiopsy demonstrating a “UIP” pattern or Multidisciplinary Discussion and Diagnosis as per ATS guidelines."
Patients with an extent of fibrosis ≥20% as per an HRCT of the chest performed within 12 months prior to Visit 1 or during the screening period (if not available) and confirmed by central review.
Patients with a FVC ≥45% predicted at Visit 1. Predicted normal values will be calculated according to Global Lung Initiative (GLI).
Patients with haemoglobin-corrected diffusing capacity of the lungs for carbon monoxide (DLCO) ≥20% predicted at Visit 1.
Further inclusion criteria apply.

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Exclusion Criteria

Acute exacerbation of IPF within at least 12 weeks prior to Visit 1 and/or during the screening period (investigator-determined).
Relevant airways obstruction (pre-bronchodilator forced expiratory volume in 1 second (FEV1)/FVC <0.7) at Visit 1.
Lower respiratory tract infection requiring treatment within 4 weeks prior to Visit 1 and/or during the screening period.
Significant PH defined by any of the following: • Previous clinical or echocardiographic evidence of significant right heart failure according to investigator’s judgement • History of right heart catheterisation showing a cardiac index ≤2 L/min/m^² • PH requiring parenteral therapy with prostanoids
On nintedanib or pirfenidone treatment for less than 12 weeks prior Visit 1, planning to start nintedanib or pirfenidone within the first 12 weeks of investigational medicinal product (IMP) treatment or on combined nintedanib plus pirfenidone treatment. Newly diagnosed patients considered in need of SoC treatment during the next 12 weeks by the treating physician, who would be withheld SoC treatment only for the sake of participation in the trial, should also be excluded.
Cardiovascular comorbidities including o Severe hypertension (uncontrolled under treatment≥160/100 mmHg at multiple occasions) within 3 months of Visit 1 o Myocardial infarction, stroke, or transient ischemic attack within 6 months of Visit 1 o Unstable cardiac angina within 6 months of Visit 1
Life expectancy for any concomitant disease other than IPF <2.5 years (investigator assessment).
Further exclusion criteria apply.