A Study to Test How Taking BI 1015550 for 12 Weeks Affects Lung Function in People With Idiopathic Pulmonary Fibrosis (IPF)

• BI 1015550 (Drug): 18 milligram (mg) BI 1015550 taken orally as film-coated tablets (1x 6mg tablet, 1x 12 mg tablet) twice daily (36 mg daily), in the morning and in the evening for 12 weeks.
• Placebo (Drug): placebo matching BI 1015550 taken orally as film-coated tablets (matching the respective BI 1015550 tablets) twice daily, in the morning and in the evening for 12 weeks.

Primary outcomes

• The Change From Baseline in Forced Vital Capacity (FVC) at 12 Weeks [Baseline (day 1) and week 12.]: The change from baseline in Forced vital capacity (FVC) at 12 weeks. Data were analysed with a restricted maximum likelihood (REML)-based approach using a mixed model with repeated measures (MMRM). The analysis included the fixed, categorical effect of treatment at each visit, and the fixed, continuous effects of baseline FVC at each visit. Visit was treated as the repeated measure, with an unstructured covariance structure used to model the within-patient measurements.

Secondary outcomes

• The Number of Patients With Treatment Emergent Adverse Event [From the start of treatment till the end of treatment + 7 days residual effect period, an average of 87.4 days.]: The number of patients with any adverse event during the on-treatment period.

Sex: All, ages: 40 Years to any

Inclusion Criteria:

1. Patients aged ≥40 years when signing the informed consent.
2. Diagnosis:

   1. IPF based on 2018 ATS/ERS/JRS/ALAT Guideline as confirmed by the investigator based on chest High Resolution Computed Tomography Scan (HRCT) scan taken within 12 months of Visit 1 and if available surgical lung biopsy.

      and
   2. Usual interstitial pneumonia (UIP) or probable UIP HRCT pattern consistent with the clinical diagnosis of IPF, as confirmed by central review prior to Visit 2*

      * if indeterminate HRCT finding IPF may be confirmed locally by (historical) biopsy
3. Stable for at least 8 weeks prior to Visit 1. Patients have to be either :

   * not on therapy with nintedanib or pirfenidone for at least 8 weeks prior to Visit 1 (combination of nintedanib plus pirfenidone not allowed), or
   * on stable* therapy with nintedanib or pirfenidone for at least 8 weeks prior to Visit 1 and planning to stay stable on this background therapy after randomisation.

   \[*stable therapy is defined as the individually and general tolerated regimen of either pirfenidone or nintedanib\]
4. Forced Vital Capacity (FVC) ≥45% of predicted normal at Visit 1
5. Diffusion capacity of the lung for carbon monoxide (DLCO) (corrected for haemoglobin \[Hb\] \[Visit 1\]) ≥ 25% to < 80% of predicted normal at Visit 1.
6. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.

Exclusion Criteria:

1. Relevant airways obstruction (pre-bronchodilator Forced Expiratory Volume in one second (FEV1)/Forced Vital Capacity (FVC) < 0.7) at Visit 1.
2. In the opinion of the Investigator, other clinically significant pulmonary abnormalities.
3. Acute IPF exacerbation within 4 months prior to screening and/or during the screening period (investigator-determined).
4. Lower respiratory tract infection requiring antibiotics within 4 weeks prior to Visit 1 and/or during the screening period.
5. Major surgery (major according to the investigator's assessment) performed within 3 months prior to Visit 1 or planned during the course of the trial. (Being on a transplant list is allowed).
6. Any documented active or suspected malignancy or history of malignancy within 5 years prior to Visit 1, except appropriately treated basal cell carcinoma of the skin, "under surveillance" prostate cancer or in situ carcinoma of uterine cervix.
7. Evidence of active infection (chronic or acute) based on clinical exam or laboratory findings at Visit 1 or at Visit 2.
8. Any suicidal behaviour in the past 2 years (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behavior).
9. The patient has a confirmed infection with SARS-CoV-2 within the 4 weeks prior to Visit 1 and/or during the screening period.

Further exclusion criteria apply.

Participant flow

Outcome results

• The Change From Baseline in Forced Vital Capacity (FVC) at 12 Weeks (Primary), Mean, Milliliter: Placebo - Antifibrotics at Baseline -77.70 (-124.87 to -30.53); BI 1015550 - Antifibrotics at Baseline 2.72 (-33.46 to 38.89); Placebo - Non-antifibrotics at Baseline -95.62 (-157.13 to -34.10); BI 1015550 - Non-antifibrotics at Baseline 6.10 (-39.67 to 51.88)
• The Number of Patients With Treatment Emergent Adverse Event (Secondary), Count of participants, Participants: Placebo - Antifibrotics at Baseline 5; BI 1015550 - Antifibrotics at Baseline 18; Placebo - Non-antifibrotics at Baseline 5; BI 1015550 - Non-antifibrotics at Baseline 9

Adverse events

Time frame: From the start of treatment till the end of treatment + 7 days residual effect period, an average of 87.4 days.

Serious adverse events by term

Other adverse events by term

• Results publication: Richeldi L, Azuma A, Cottin V, Hesslinger C, Stowasser S, Valenzuela C, Wijsenbeek MS, Zoz DF, Voss F, Maher TM; 1305-0013 Trial Investigators. Trial of a Preferential Phosphodiesterase 4B Inhibitor for Idiopathic Pulmonary Fibrosis. N Engl J Med. 2022 Jun 9;386(23):2178-2187. doi: 10.1056/NEJMoa2201737. Epub 2022 May 15. PMID 35569036

• Study Protocol (PDF, 2020-09-09)
• Statistical Analysis Plan (PDF, 2021-10-08)

NIH grants: 2019