A Study to Find Out Whether BI 1015550 Improves Lung Function in People With Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs)

NCT05321082
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Phase
Phase 3
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Recruitment status
Completed
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Participants
1,178
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Lead sponsor
Boehringer Ingelheim
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Start date
2022-11-16
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Number of sites
400
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Summary
This study is open to adults with Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs). People who have a form of PF-ILD other than Idiopathic Pulmonary Fibrosis (IPF) can join the study. If they already take nintedanib, they can continue treatment throughout the study. The purpose of this study is to find out whether a medicine called BI 1015550 helps people with PF-ILD. Participants are put into 3 groups randomly, which means by chance. Participants in 2 groups take different doses of BI 1015550 as tablets twice a day. Participants in the placebo group take placebo tablets twice a day. Placebo tablets look like BI 1015550 tablets but do not contain any medicine. Participants are in the study for up to two and a half years. During the first year, they visit the study site 10 times. Afterwards, they visit the study site every 3 months. The doctors regularly test participants' lung function. The results of the lung function tests are compared between the groups. The doctors also regularly check participants' health and take note of any unwanted effects.
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Short title
A Study to Find Out Whether BI 1015550 Improves Lung Function in People With Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs)
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Official title
A Double Blind, Randomized, Placebo-controlled Trial Evaluating the Efficacy and Safety of BI 1015550 Over at Least 52 Weeks in Patients With Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs)
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Control arm
Placebo
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Registry reports results
Yes
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Listing at source
Listed
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Recruitment status
Completed
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Phase
Phase 3
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Study type
Interventional
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Completion date
2025-04-14
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First posted
2022-04-11
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Registry last updated
2026-01-09
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Primary completion date
2024-12-18
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Start date
2022-11-16
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Actual participants
1,178
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Participants
1,178
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Participant count basis
Actual
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Protocol amendments
6
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Number of sites
400
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Boehringer Ingelheim
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05321082
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ClinicalTrials.gov ID
NCT05321082
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Quadruple masking
Masked roles
Participants, Care providers, Investigators, Outcome assessors
Sources for study design
clinicaltrials.gov

  1. Absolute Change From Baseline in Forced Vital Capacity (FVC) in Milliliters [mL] at Week 52

    Timeframe: The MMRM model is a longitudinal analysis, and it incorporated FVC measurements change from baseline at Week 1, Week 2, Week 6, Week 12, Week 18, Week 26, Week 36, Week 44 and Week 52. Data presented is the FVC adjusted change from baseline at Week 52.

    The absolute change from baseline in forced vital capacity (FVC) in milliliters \[mL\] at Week 52 is reported. The absolute change from baseline in FVC was analyzed by a restricted maximum likelihood (REML)-based mixed model with repeated measurements (MMRM) comparing the change from baseline in FVC at Week 52 between treatment groups. The analysis included the fixed, categorical effects of treatment, baseline intake of antifibrotic (AF) treatment, and baseline High-resolution Computed Tomography (HRCT) pattern at each visit, as well as the fixed continuous effects of baseline FVC value at each visit. Visits were treated as a repeated measure with an unstructured covariance structure used to model within-patient measurements.

  1. Key Secondary Endpoint: Time to First Occurrence of Any of the Components of the Composite Endpoint: Time to First Acute ILD Exacerbation, First Hospitalisation for Respiratory Cause, or Death (Whichever Occurred First) Over the Duration of the Trial

    Timeframe: From first administration of trial drug (Nerandomilast or Placebo) till end of study, up to 26.2 months.

    Time to first occurrence of any of the components of the composite endpoint - acute interstitial lung disease (ILD) exacerbation, first hospitalisation for respiratory cause, or death (whichever occurred first) - is reported as the number of participants who experienced any of these events during the trial. Acute exacerbation of ILD describes an acute, clinically significant, respiratory deterioration characterized by evidence of new widespread alveolar abnormality with all of the following: Acute worsening or development of dyspnea typically with less than 1 month duration, computed tomography with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with fibrosing ILD, and deterioration not fully explained by cardiac failure or fluid overload. If more than one component occurred on the same day, the patient was counted under the first event according to the following hierarchy: acute ILD exacerbation, hospitalization, death.

  2. Time to First Acute ILD Exacerbation or Death Over the Duration of the Trial

    Timeframe: From first administration of trial drug (Nerandomilast or Placebo) till end of study, up to 26.2 months.

    Time to first acute ILD exacerbation or death over the duration of the trial is reported as the number of patients who experienced either event. Acute exacerbation of ILD describes an acute, clinically significant, respiratory deterioration characterized by evidence of new widespread alveolar abnormality with all of the following: Acute worsening or development of dyspnea typically with less than 1 month duration, computed tomography with new bilateral ground-glass opacity and/or consolidation superimposed on a background pattern consistent with fibrosing ILD, and deterioration not fully explained by cardiac failure or fluid overload. If more than one component occurred on the same day, the patient was counted under the first event according to the following hierarchy: acute IPF exacerbation followed by death.

  3. Time to Hospitalisation for Respiratory Cause or Death Over the Duration of the Trial

    Timeframe: From first administration of trial drug (Nerandomilast or Placebo) till end of study, up to 26.2 months.

    Time to hospitalisation for respiratory cause or death over the duration of the trial is reported as the number of participants who experienced either event. Hospitalizations due to respiratory causes were recorded on a specific non-elective hospitalization CRF page. This page captured the hospitalization date, confirmation of a respiratory cause, and the primary admission diagnosis. Time to death was based either on the date of death on the adverse event (AE) report for patients with AEs leading to death or was based on the information from the vital status assessment.

  4. Time to Death Over the Duration of the Trial

    Timeframe: From first administration of trial drug (Nerandomilast or Placebo) till end of study, up to 26.2 months.

    Time to death over the duration of the trial is reported as the number of participants who died. Time to death was based either on the date of death on the AE report for patients with AEs leading to death or based on the information from the vital status assessment.

  5. Absolute Change From Baseline in Forced Vital Capacity (FVC) Percent (%) Predicted at Week 52

    Timeframe: The MMRM model is a longitudinal analysis, and it incorporated FVC % predicted change from baseline at Week 1, Week 2, Week 6, Week 12, Week 18, Week 26, Week 36, Week 44 and Week 52. Data presented is change from baseline in FVC % predicted at Week 52.

    Absolute change from baseline in forced vital capacity (FVC) percent (%) predicted at Week 52 is reported. Analysis was based on a Mixed Model for Repeated Measures (MMRM), with fixed, categorical effects of treatment at each visit, baseline antifibrotic therapy at each visit, baseline HRCT pattern at each visit, the fixed continuous effects of baseline FVC \[% pred\] at each visit and unstructured covariance for repeated measures. Baseline antifibrotic therapy and HRCT pattern as entered in the CRF pages were used as covariates.

  6. Time to Absolute Decline in Forced Vital Capacity (FVC) % Predicted of >10% From Baseline or Death Over the Duration of the Trial

    Timeframe: From first administration of trial drug (Nerandomilast or Placebo) till end of study, up to 26.2 months.

    The time to absolute decline of more than 10% from baseline in forced vital capacity (FVC) percent predicted, or death, over the duration of the trial is reported as the number of participants who experienced either event. If multiple components occurred on the day of first event, then the patient was only counted in the first component based on the following hierarchy: absolute decline in FVC % predicted of \> 10% followed by death.

  7. Absolute Change From Baseline in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) % Predicted (Corrected for Hb) at Week 52

    Timeframe: The MMRM model is a longitudinal analysis and it incorporated DLCO measurements from baseline (Week -8 to Week -1) and Week 12, Week 26, and Week 52. The data represent the adjusted Least Square Means for change from baseline at Week 52.

    The absolute change from baseline in Diffusing Capacity of the Lungs for Carbon Monoxide percent predicted (corrected for hemoglobin, Hb) at Week 52 is reported.. Analysis was based on a Mixed Model for Repeated Measures (MMRM), with fixed, categorical effects of treatment at each visit, baseline antifibrotic therapy at each visit, baseline HRCT pattern at each visit, the fixed continuous effects of baseline DLCO \[% pred\] at each visit and unstructured covariance for repeated measures. Baseline antifibrotic therapy and HRCT pattern as entered in the CRF pages were used as covariates.

  8. Time to Absolute Decline in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) Percentage Predicted by More Than 15% From Baseline or Death, Measured Over the Duration of the Trial

    Timeframe: From first administration of trial drug (Nerandomilast or Placebo) till end of study, up to 26.2 months.

    Time to absolute decline in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) percentage predicted by more than 15% from baseline or death, measured over the duration of the trial is reported as the number of participants who experienced either event. The Predicted DLCO value was corrected for hemoglobin (Hb). If more than one component occurred on the same day, the patient was counted under the first event according to the hierarchy: Absolute decline in DLCO % predicted of \> 15%, followed by Death.

  9. Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Dyspnea Domain Score at Week 52

    Timeframe: The MMRM model is a longitudinal analysis and it incorporated L-PF measurements from baseline (Week -8 to Week -1) and Week 12, Week 26, Week 36, Week 44 and Week 52. The data represent the adjusted Least Square Means for change from baseline at Week 52.

    The absolute change from baseline in Living with Pulmonary Fibrosis (L-PF) Symptoms Dyspnea domain score at Week 52 is reported. The Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44-item tool consisting of two modules: Symptoms (23 items) and Impacts (21 items). The Symptoms module yields three domain scores: Dyspnoea, Cough, and Fatigue, as well as a Total Symptoms score. Scoring is based on the mean of item ratings within each domain, multiplied by 100. Scores range from 0 to 100, with higher scores indicating greater impairment. This endpoint was analyzed using a Mixed Model for Repeated Measures (MMRM). The model included fixed effects for treatment, baseline antifibrotic therapy, baseline HRCT pattern, and fixed continuous effect of baseline L-PF dyspnea score at each visit, with an unstructured covariance for repeated measures. Baseline antifibrotic therapy and HRCT pattern as entered in the CRF pages were covariates.

  10. Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Cough Domain Score at Week 52

    Timeframe: The MMRM model is a longitudinal analysis and it incorporated L-PF measurements from baseline (Week -8 to Week -1) and Week 12, Week 26, Week 36, Week 44 and Week 52. The data represent the adjusted Least Square Means for change from baseline at Week 52.

    The absolute change from baseline in the L-PF Cough domain score at Week 52 is reported. The Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44-item tool consisting of two modules: Symptoms (23 items) and Impacts (21 items). The Symptoms module yields three domain scores: Dyspnea, Cough, and Fatigue, as well as a Total Symptoms score. Scoring is based on the mean of item ratings within each domain, multiplied by 100. Scores range from 0 to 100, with higher scores indicating greater impairment. This endpoint was analyzed using a Mixed Model for Repeated Measures (MMRM). The model included fixed effects for treatment, baseline antifibrotic therapy, baseline HRCT pattern, and fixed continuous effect of baseline L-PF dyspnea score at each visit, with an unstructured covariance for repeated measures. Baseline antifibrotic therapy and HRCT pattern as entered in the CRF pages were covariates.

  11. Absolute Change From Baseline in Living With Pulmonary Fibrosis (L-PF) Symptoms Fatigue Domain Score at Week 52

    Timeframe: The MMRM model is a longitudinal analysis and it incorporated L-PF measurements from baseline (Week -8 to Week -1) and Week 12, Week 26, Week 36, Week 44 and Week 52. The data represent the adjusted Least Square Means for change from baseline at Week 52.

    The absolute change from baseline in the L-PF Fatigue domain score at Week 52 is reported. The Living with Pulmonary Fibrosis (L-PF) questionnaire is a 44-item tool consisting of two modules: Symptoms (23 items) and Impacts (21 items). The Symptoms module yields three domain scores: Dyspnea, Cough, and Fatigue, as well as a Total Symptoms score. Scoring is based on the mean of item ratings within each domain, multiplied by 100. Scores range from 0 to 100, with higher scores indicating greater impairment. This endpoint was analyzed using a Mixed Model for Repeated Measures (MMRM). The model included fixed effects for treatment, baseline antifibrotic therapy, and baseline HRCT pattern at each visit, and fixed continuous effect of baseline L-PF Fatigue score at each visit, with an unstructured covariance for repeated measures. Baseline antifibrotic therapy and HRCT pattern as entered in the CRF pages were covariates.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  1. Patients ≥18 years old at the time of signed informed consent.

  2. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.

  3. Diagnosis of progressive fibrosing ILD other than IPF (physician confirmed).

  4. Patients may be either:

    • on a stable therapy* with nintedanib for at least 12 weeks prior to Visit 1 and during screening and are planning to stay on this background treatment after randomization. (*stable therapy is defined as a tolerated regimen of nintedanib (with no dose changes) for at least 12 weeks)
    • not on treatment with nintedanib for at least 8 weeks prior to Visit 1 and during the screening period (e.g. either Antifibrotic (AF)-treatment naïve or previously discontinued) and do not plan to start or re-start antifibrotic treatment.

  5. Forced Vital Capacity (FVC) ≥45% of predicted normal at Visit 1.

  6. DLCO ≥25% of predicted normal corrected for hemoglobin (Hb) at Visit 1.

  7. Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control. WOCBP taking oral contraceptives (OCs) also have to use one barrier method

  8. Patients treated with permitted immunosuppressive agents (other than corticosteroids) for an underlying systemic disease (e.g. Methotrexate (MTX), Azathioprine (AZA)) need to be on a stable treatment for at least 12 weeks prior to Visit 1 and during the screening period.

  1. Prebronchodilator Forced Expiratory Volume in 1 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 Interstitial Lung Disease (ILD) exacerbation within 3 months prior to Visit 1 and/or during the screening period (investigator-determined).
  4. Relevant chronic or acute infections including human immunodeficiency virus (HIV) and viral hepatitis.
  5. Patients having developed ILD due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection/coronavirus disease 2019 (COVID-19) within 12 months of screening (based on investigators judgement).
  6. Major surgery (major according to the investigator's assessment) performed within 6 weeks prior to Visit 2 or planned during the trial period, e.g. hip replacement. Registration on lung transplantation list would not be considered as planned major surgery.
  7. 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, in situ squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix.
  8. Aspartate aminotransferase (AST) or Alanine Aminotransferase (ALT) >2.5 x upper limit of normal (ULN) or total Bilirubin >1.5 x ULN at Visit 1.

Further exclusion criteria apply.

Sources for eligibility
clinicaltrials.gov

  • University of Alabama at BirminghamBirmingham, United States
  • University of ArizonaTucson, United States
  • University of Southern CaliforniaLos Angeles, United States
  • Cedars-Sinai Medical CenterLos Angeles, United States
  • University of California Los AngelesLos Angeles, United States
  • University of California DavisSacramento, United States
  • National Jewish HealthDenver, United States
  • Yale University School of MedicineNew Haven, United States
  • Christiana HospitalNewark, United States
  • St. Francis Medical InstituteClearwater, United States
  • University of Florida Health Shands HospitalGainesville, United States
  • Clinical Research Specialists LLCKissimmee, United States
  • Advanced Pulmonary Research InstituteLoxahatchee Groves, United States
  • Destin Pulmonary Critical CareSanta Rosa Beach, United States
  • Piedmont Physicians Pulmonary & Sleep Medicine of BuckheadAtlanta, United States
  • The Emory ClinicAtlanta, United States
  • Evanston Hospital Pulmonary ClinicEvanston, United States
  • University of Kansas Medical CenterKansas City, United States
  • Tulane University Hospital and ClinicNew Orleans, United States
  • Johns Hopkins HospitalBaltimore, United States
  • Massachusetts General HospitalBoston, United States
  • Brigham and Women's HospitalBoston, United States
  • St. Elizabeth's Medical CenterBoston, United States
  • Beth Israel Deaconess Medical CenterBoston, United States
  • Infinity Medical ResearchNorth Dartmouth, United States

And 375 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

Other registry identifiers

  • 2022-001134-11
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)