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

A Randomised, Double-blind, Placebo-controlled Parallel Group Study in IPF Patients Over 12 Weeks Evaluating Efficacy, Safety and Tolerability of BI 1015550 Taken Orally

This study is open to adults with idiopathic pulmonary fibrosis (IPF) who are at least 40 years old. People taking standard medicines for IPF, including antifibrotic medicines, can continue taking them throughout the study.

The purpose of the study is to find out whether a medicine called BI 1015550 can slow down the worsening of lung function. Participants are in the study for about 4 months. During this time, they visit the study site about 7 times. At the beginning, they visit the study site every 2 weeks.

After 1 month of treatment, they visit the study site every 4 weeks.

The participants are put into 2 groups by chance. 1 group gets BI 1015550. The other group gets placebo. Placebo tablets look like BI 1015550 tablets but contain no medicine. The participants take BI 1015550 or placebo tablets twice a day.

The participants have lung function tests at study visits. The results of the lung function tests are compared between the BI 1015550 group and the placebo group. The doctors also regularly check the general health of the participants.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: Placebo; Drug: BI 1015550

• Study Type: Interventional
• Enrollment (Actual): 147
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • C.a.b.a, Argentina, C1027AAP
    • Centro de Investigaciones Metabólicas (CINME)
• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Austria
  • Graz, Austria, 8036
    • LKH-Univ. Hospital Graz
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • St. Paul's Hospital
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 2Z3
      • Dr. Georges-L.-Dumont University Hospital Centre
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V6
      • Queen's University
    • Windsor, Ontario, Canada, N8X 1T3
      • Dr. Syed Anees Medicine Professional Corporation
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Centre Hospitalier de l'Universite de Montreal (CHUM)
• Chile
  • Providencia, Santiago De Chile, Chile, 7500691
    • Instituto Nacional del Tórax
  • Talca, Chile, 3465586
    • Centro de Investigación del Maule
• China
  • Beijing, China, 100032
    • Peking Union Medical College Hospital
  • Changchun, China, 130041
    • The Second Hospital of Jilin University
  • Chengdu, China, 610041
    • West China Hospital
  • Shanghai, China, 200433
    • Shanghai Pulmonary Hospital
  • Shanghai, China, 200032
    • Zhongshan Hospital Fudan University
• Czechia
  • Praha, Czechia, 180 81
    • University Hospital Na Bulovce, Prague
  • Praha 4 - Krc, Czechia, 140 59
    • University Thomayer's Hospital
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus University Hospital
  • Hellerup, Denmark, 2900
    • Herlev and Gentofte Hospital
  • Odense C, Denmark, 5000
    • Odense University Hospital
• Finland
  • Helsinki, Finland, 00290
    • HYKS Keuhkosairauksien tutkimusyksikkö
  • Kuopio, Finland, 70210
    • KYS, Keuhkosairauksien
  • Oulu, Finland, FIN-90220
    • Oulun yliopistollinen keskussairaala
  • Tampere, Finland, 33521
    • Tampere University Hospital
  • Turku, Finland, 20520
    • TYKS
• Germany
  • Coswig, Germany, 01640
    • Fachkrankenhaus Coswig GmbH
  • Essen, Germany, 45239
    • Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
  • Heidelberg, Germany, 69126
    • Thoraxklinik-Heidelberg gGmbH am Universitätsklinikum Heidelberg
  • Immenhausen, Germany, 34376
    • Lungenfachklinik Immenhausen
  • Münster, Germany, 48149
    • Universitätsklinikum Münster
• Greece
  • Athens, Greece, 15125
    • Athens Medical Center
  • Crete, Greece, 71110
    • University General Hospital of Heraklion
  • Patras, Greece, 26504
    • Univ. Gen. Hosp. of Patras
• Hungary
  • Budapest, Hungary, 1085
    • Semmelweis University
• Italy
  • Foggia, Italy, 71100
    • Ospedale Colonnello D Avanzo
  • Padova, Italy, 35128
    • Azienda Ospedaliera Universitaria di Padova
  • Roma, Italy, 00168
    • Poli Univ A. Gemelli
  • Siena, Italy, 53100
    • A.O.U. Senese Policlinico Santa Maria alle Scotte
• Japan
  • Aichi, Seto, Japan, 489-8642
    • Tosei General Hospital
  • Fukuoka, Fukuoka, Japan, 810-8563
    • National Hospital Organization Kyushu Medical Center
  • Kanagawa, Yokohama, Japan, 236-0051
    • Kanagawa Cardiovascular and Respiratory Center
  • Osaka, Sakai, Japan, 591-8555
    • National Hospital Organization Kinki-Chuo Chest Medical Center
  • Shizuoka, Hamamatsu, Japan, 431-3192
    • Hamamatsu University Hospital
  • Tokyo, Shinjuku-ku, Japan, 162-8655
    • Center Hospital of the National Center for Global Health and Medicine
• Korea, Republic of
  • Bucheon, Korea, Republic of, 14647
    • The Catholic University of Korea, Bucheon St.Mary's Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
• Netherlands
  • Heerlen, Netherlands, 6419 PC
    • Zuyderland Medisch Centrum
  • Nieuwegein, Netherlands, 3435 CM
    • St. Antonius Ziekenhuis, locatie Nieuwegein
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus Medisch Centrum
• Poland
  • Gdansk, Poland, 80-214
    • University Clinical Center, Gdansk
• Russian Federation
  • Moscow, Russian Federation, 105275
    • Federal state budgetary scientific institution "Research Institute of occupational medicine named after academician N. F. Izmerov
  • Moscow, Russian Federation, 119992
    • Moscow 1st State Med.Univ.n.a.I.M.Sechenov
  • Yaroslavl, Russian Federation, 150003
    • Emergency Clinical Hospital n. a. N. V. Solovyev, Yaroslavl
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08006
    • Policlinica Barcelona
  • L'Hospitalet de Llobregat, Spain, 08907
    • Hospital De Bellvitge
  • Madrid, Spain, 28006
    • Hospital La Princesa
  • Oviedo, Spain, 33011
    • Hospital Central de Asturias
  • Palma de Mallorca, Spain, 07120
    • Hospital Son Espases
• Ukraine
  • Dnyepropyetrovsk, Ukraine, 49074
    • Dnyepropyetrovsk Medical Academy, Clinical Hospital No. 6
  • Kyiv, Ukraine, 03680
    • Instit.Phthisiology&Pulmon.na Yanovskiy,Non-Specif.Lung,Kyiv
• United Kingdom
  • Bristol, United Kingdom, BS10 5NB
    • Southmead Hospital
  • London, United Kingdom, SW3 6NP
    • Royal Brompton Hospital
• United States
  • Florida
    • Clearwater, Florida, United States, 33765
      • St. Francis Medical Institute
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic, Rochester
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • The Lung Research Center, LLC
  • Nebraska
    • Omaha, Nebraska, United States, 68124
      • Creighton University
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Southeastern Research Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • Texas
    • San Antonio, Texas, United States, 78229
      • Diagnostics Research Group
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo, Antifibrotics at baseline; Idiopathic pulmonary fibrosis (IPF) patients on stable antifibrotic treatment with nintedanib or pirfenidone at baseline were administered 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. During the 12-weeks of administration of BI 1015550 patients stayed on their stable background therapy of nintedanib or prifenidone.	Drug: Placebo; 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.
Experimental: BI 1015550, Antifibrotics at baseline; Idiopathic pulmonary fibrosis (IPF) patients on stable antifibrotic treatment with nintedanib or pirfenidone at baseline were administered 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. During the 12-weeks of administration of BI 1015550 patients stayed on their stable background therapy of nintedanib or prifenidone.	Drug: BI 1015550; 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 Comparator: Placebo, Non-antifibrotics at baseline; Idiopathic pulmonary fibrosis (IPF) patients not on stable antifibrotic treatment at baseline were administered 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.	Drug: Placebo; 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.
Experimental: BI 1015550, Non-antifibrotics at baseline; Idiopathic pulmonary fibrosis (IPF) patients not on stable antifibrotic treatment at baseline were administered 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.	Drug: BI 1015550; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Change From Baseline in Forced Vital Capacity (FVC) at 12 Weeks	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.	Baseline (day 1) and week 12.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Number of Patients With Treatment Emergent Adverse Event	The number of patients with any adverse event during the on-treatment period.	From the start of treatment till the end of treatment + 7 days residual effect period, an average of 87.4 days.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2020
• Primary Completion (Actual): October 6, 2021
• Study Completion (Actual): October 15, 2021

Study Registration Dates

• First Submitted: June 4, 2020
• First Submitted That Met QC Criteria: June 4, 2020
• First Posted (Actual): June 5, 2020

Study Record Updates

• Last Update Posted (Actual): November 1, 2022
• Last Update Submitted That Met QC Criteria: October 5, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
• Other Study ID Numbers: 1305-0013; 2019-004167-45 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

The data shared are the raw clinical study data sets.

• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No