Idiopathic Pulmonary Fibrosis
Conditions
Brief summary
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.
Interventions
DRUGBI 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.
DRUGPlacebo
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.
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Argentina, Australia, Austria, Canada, Chile, China, Czechia, Denmark, Finland, Germany, Greece, Hungary, Italy, Japan, Netherlands, Poland, Russia, South Korea, Spain, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
This was a trial with a randomised, placebo-controlled, double-blind, parallel-group design over 12 weeks, including a screening period of up to 44 days, a 12-week treatment period, and a 1-week follow-up period in patients with idiopathic pulmonary fibrosis (IPF) stratified by baseline antifibrotic treatment (Non-AF stratum: patients not on antifibrotic treatment at baseline; AF stratum: stable antifibrotic treatment with nintedanib or pirfenidone at baseline).
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo - Antifibrotics at Baseline Idiopathic pulmonary fibrosis (IPF) patients on 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 background therapy of nintedanib or prifenidone. | 25 |
| BI 1015550 - Antifibrotics at Baseline Idiopathic pulmonary fibrosis (IPF) patients on 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 background therapy of nintedanib or prifenidone. | 49 |
| Placebo - Non-antifibrotics at Baseline Idiopathic pulmonary fibrosis (IPF) patients not on 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. Patients were not expected to start antifibrotic treatment during the 12 weeks of placebo treatment. | 25 |
| BI 1015550 - Non-antifibrotics at Baseline Idiopathic pulmonary fibrosis (IPF) patients not on 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. Patients were not expected to start antifibrotic treatment during the 12 weeks of BI 1015550 treatment. | 48 |
| Total | 147 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 10 | 0 | 3 |
| Overall Study | poor-compliance | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | BI 1015550 - Non-antifibrotics at Baseline | Placebo - Non-antifibrotics at Baseline | BI 1015550 - Antifibrotics at Baseline | Placebo - Antifibrotics at Baseline |
|---|---|---|---|---|---|
| Age, Continuous | 69.6 years STANDARD_DEVIATION 8.4 | 69.9 years STANDARD_DEVIATION 8.3 | 71.8 years STANDARD_DEVIATION 9.3 | 69.3 years STANDARD_DEVIATION 6.6 | 67.5 years STANDARD_DEVIATION 10.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 5 Participants | 4 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 134 Participants | 43 Participants | 21 Participants | 46 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Forced vital capacity (FVC) | 2811.946 Milliliter STANDARD_DEVIATION 845.625 | 2782.938 Milliliter STANDARD_DEVIATION 835.104 | 2864.920 Milliliter STANDARD_DEVIATION 1015.104 | 2875.551 Milliliter STANDARD_DEVIATION 752.818 | 2690.000 Milliliter STANDARD_DEVIATION 889.985 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 32 Participants | 12 Participants | 4 Participants | 12 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 115 Participants | 36 Participants | 21 Participants | 37 Participants | 21 Participants |
| Sex: Female, Male Female | 34 Participants | 14 Participants | 8 Participants | 5 Participants | 7 Participants |
| Sex: Female, Male Male | 113 Participants | 34 Participants | 17 Participants | 44 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 1 / 49 | 0 / 25 | 1 / 48 |
| other Total, other adverse events | 10 / 25 | 24 / 49 | 5 / 25 | 18 / 48 |
| serious Total, serious adverse events | 0 / 25 | 3 / 49 | 5 / 25 | 3 / 48 |
Outcome results
Primary
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.
Time frame: Baseline (day 1) and week 12.
Population: Full Analysis Set (FAS): all patients who received at least one dose of trial drug and who had a baseline and at least one post-baseline measurement available for Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1) or Diffusion Capacity of the Lung for Carbon Monoxide (DLCO).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo - Antifibrotics at Baseline | The Change From Baseline in Forced Vital Capacity (FVC) at 12 Weeks | -77.70 Milliliter |
| BI 1015550 - Antifibrotics at Baseline | The Change From Baseline in Forced Vital Capacity (FVC) at 12 Weeks | 2.72 Milliliter |
| Placebo - Non-antifibrotics at Baseline | The Change From Baseline in Forced Vital Capacity (FVC) at 12 Weeks | -95.62 Milliliter |
| BI 1015550 - Non-antifibrotics at Baseline | The Change From Baseline in Forced Vital Capacity (FVC) at 12 Weeks | 6.10 Milliliter |
Comparison: Adjusted means in the placebo group were combined with the meta-analytic predictive priors derived based on the clinical trials in the nintedanib clinical development program in IPF. In order to evaluate the treatment effects, the posterior distribution for the treatment difference of BI 1015550 versus placebo with respect to the primary endpoint was used. The median of the posterior distribution for the treatment difference (and 95% credible intervals) was calculated.95% CI: [29.5, 154.2]
Comparison: Adjusted means in the placebo group were combined with the meta-analytic predictive priors derived based on the clinical trials in the nintedanib clinical development program in IPF. In order to evaluate the treatment effects, the posterior distribution for the treatment difference of BI 1015550 versus placebo with respect to the primary endpoint was used. The median of the posterior distribution for the treatment difference (and 95% credible intervals) was calculated.95% CI: [6.3, 125.5]
Secondary
The Number of Patients With Treatment Emergent Adverse Event
The number of patients with any adverse event during the on-treatment period.
Time frame: From the start of treatment till the end of treatment + 7 days residual effect period, an average of 87.4 days.
Population: Treated Set (TS): all patients who received at least one dose of trial drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo - Antifibrotics at Baseline | The Number of Patients With Treatment Emergent Adverse Event | 5 Participants |
| BI 1015550 - Antifibrotics at Baseline | The Number of Patients With Treatment Emergent Adverse Event | 18 Participants |
| Placebo - Non-antifibrotics at Baseline | The Number of Patients With Treatment Emergent Adverse Event | 5 Participants |
| BI 1015550 - Non-antifibrotics at Baseline | The Number of Patients With Treatment Emergent Adverse Event | 9 Participants |