BI 1015550 for Interstitial Lung Disease

Recruiting at 523 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Boehringer Ingelheim

Must be taking: Nintedanib

Disqualifiers: HIV, Viral hepatitis, Recent COVID-19, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 10

Duration: 31 months

1178 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if BI 1015550 can help adults with certain progressive lung diseases. Participants take the medicine as tablets, and their lung function is checked over time to see if it improves. The study aims to find out if this new treatment can slow down the worsening of their lung condition.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on nintedanib, you can continue taking it during the study. If you are on other immunosuppressive agents, you need to be on a stable treatment for at least 12 weeks before starting the trial.

What data supports the effectiveness of the drug BI 1015550 for Interstitial Lung Disease?

A trial published in the New England Journal of Medicine investigated BI 1015550 as a potential treatment for idiopathic pulmonary fibrosis (IPF), a condition similar to interstitial lung disease, and compared it to a placebo to assess its effectiveness. ^{1 2 3 4 5}

Is BI 1015550 safe for humans?

In a study for idiopathic pulmonary fibrosis, BI 1015550 was compared to a placebo, and the study reported additional medical issues (adverse events) during the trial. This suggests that safety data was collected, but specific details on the safety outcomes are not provided in the summary. ^{1 3 4 6 7}

How is the drug BI 1015550 different from other treatments for interstitial lung disease?

BI 1015550 is unique because it is a phosphodiesterase 4 (PDE4) inhibitor with antifibrotic properties, which means it helps reduce lung scarring by targeting a specific enzyme pathway. This mechanism is different from other approved antifibrotic drugs like nintedanib and pirfenidone, which have been used for idiopathic pulmonary fibrosis and other interstitial lung diseases. ^{3 8 9 10 11}

Eligibility Criteria

Adults with Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs) other than Idiopathic Pulmonary Fibrosis can join this study. They must have a certain level of lung function, not have had recent severe respiratory infections or lung exacerbations, and women must use effective birth control. People with recent major surgeries or certain liver issues cannot participate.

Inclusion Criteria

You must be able to breathe out a certain amount of air, which is at least 45% of what is expected for someone your age and size.

My doctor confirmed I have a worsening lung condition that is not IPF.

Your lung function test shows that the amount of oxygen your lungs can transfer to your blood is between 25% and 90% of what is expected for someone your age and size.

Exclusion Criteria

I haven't had cancer, except for certain skin or cervical cancers, in the last 5 years.

Your lung function test shows that you have trouble breathing out air.

I haven't had, nor do I plan to have, any major surgeries like a hip replacement during the trial.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BI 1015550 or placebo tablets twice a day for up to 31 months

31 months

10 visits in the first year, then every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BI 1015550
• Placebo

Trial Overview The trial is testing BI 1015550 to see if it improves lung function in PF-ILD patients. Participants are randomly assigned to receive either different doses of BI 1015550 or a placebo, resembling the actual drug but without active ingredients, for up to two and a half years with regular health checks.

Participant Groups

Group I: BI 1015550 low dose Experimental Treatment 1 Intervention

Group II: BI 1015550 high dose Experimental Treatment 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Findings from Research

In a Phase 2 study involving 253 patients with unclassifiable interstitial lung disease (uILD), pirfenidone demonstrated a significant improvement in forced vital capacity (FVC) compared to placebo over 24 weeks, regardless of whether patients had undergone surgical lung biopsy (SLB).

Patients with SLB showed a mean FVC change of -90.9 mL with pirfenidone versus -146.3 mL with placebo, while those without SLB had a mean change of 8.2 mL with pirfenidone versus -85.3 mL with placebo, indicating that pirfenidone may be effective across different patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Pirfenidone vs. Placebo in Unclassifiable Interstitial Lung Disease, by Surgical Lung Biopsy Status: Data From a post-hoc Analysis. Molina-Molina, M., Kreuter, M., Cottin, V., et al.[2022]

In a study of 253 patients with unclassifiable interstitial lung disease (uILD), pirfenidone showed a significant treatment effect on lung function in patients not receiving concomitant mycophenolate mofetil (MMF), with a mean improvement in forced vital capacity (FVC) of 115.5 mL compared to placebo.

The analysis indicated that pirfenidone may be less effective in patients receiving MMF, as shown by a negligible change in FVC in that subgroup, but overall, pirfenidone was well tolerated across all groups, regardless of MMF or corticosteroid use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pirfenidone in Unclassifiable Interstitial Lung Disease: A Subgroup Analysis by Concomitant Mycophenolate Mofetil and/or Previous Corticosteroid Use. Kreuter, M., Maher, TM., Corte, TJ., et al.[2023]

In a trial involving 147 participants with idiopathic pulmonary fibrosis (IPF) across 22 countries, the medication BI 1015550 was found to effectively prevent the decline in lung function compared to a placebo.

While BI 1015550 did not lead to a higher rate of severe adverse events compared to placebo, it was associated with more cases of diarrhea, and 13 participants discontinued treatment due to medical issues, indicating the need for further studies to assess its long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plain language summary: Clinical study of BI 1015550 as a potential treatment for idiopathic pulmonary fibrosis. Richeldi, L., Azuma, A., Cottin, V., et al.[2023]

The INBUILD trial demonstrated that nintedanib significantly reduces the rate of decline in forced vital capacity (FVC) in patients with progressive fibrosing interstitial lung diseases (ILDs), particularly in those with a relative decline in FVC of 10% or more.

The trial effectively identified patients with progressive ILDs using specific criteria related to FVC decline and worsening symptoms, showing that nintedanib's efficacy was consistent across different subgroups, regardless of the severity of FVC decline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of nintedanib by inclusion criteria for progression of interstitial lung disease. Maher, TM., Brown, KK., Kreuter, M., et al.[2022]

A systematic review of six studies showed that pirfenidone, nintedanib, and pamrevlumab are all effective in slowing the decline of forced vital capacity (FVC) in patients with idiopathic pulmonary fibrosis (IPF), with pamrevlumab showing the highest effect size.

Only pirfenidone demonstrated a significant impact on all-cause mortality, suggesting it may offer additional benefits beyond just slowing FVC decline, while pamrevlumab is emerging as a promising candidate for future treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review and Meta-analysis of Pirfenidone, Nintedanib, and Pamrevlumab for the Treatment of Idiopathic Pulmonary Fibrosis. Di Martino, E., Provenzani, A., Vitulo, P., et al.[2021]

In the INBUILD trial involving 663 patients with chronic fibrosing interstitial lung diseases, nintedanib significantly reduced the rate of lung function decline (measured by forced vital capacity) compared to placebo, regardless of glucocorticoid use.

The safety profile of nintedanib remained consistent whether patients were using immunomodulatory therapies or not, suggesting it can be safely combined with these treatments in managing progressive fibrosing ILDs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nintedanib and immunomodulatory therapies in progressive fibrosing interstitial lung diseases. Cottin, V., Richeldi, L., Rosas, I., et al.[2021]

This study analyzed data from the Japanese Adverse Drug Event Report (JADER) and the FDA Adverse Event Reporting System (FAERS) to investigate the incidence of interstitial lung disease (ILD) potentially caused by antifibrotic drugs nintedanib and pirfenidone, both of which are first-line treatments for idiopathic pulmonary fibrosis (IPF).

The findings indicated that both nintedanib and pirfenidone were associated with signals for causing ILD, emphasizing the need for careful monitoring of these drugs due to their limited effectiveness and potential to induce lung damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the potential complication of interstitial lung disease associated with antifibrotic drugs using data from databases reporting spontaneous adverse effects. Nawa, H., Hamano, H., Niimura, T., et al.[2023]

In a Phase I study involving 42 healthy male subjects, BI 1015550 showed a higher incidence of drug-related adverse events (AEs) compared to placebo, with 50% of subjects experiencing AEs after a single dose, primarily headaches.

In a Phase Ic study with 15 patients suffering from idiopathic pulmonary fibrosis (IPF), 90% of those treated with BI 1015550 reported drug-related AEs, mainly gastrointestinal issues, indicating that while the drug has an acceptable safety profile, further investigation in larger trials is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I studies of BI 1015550, a preferential phosphodiesterase 4B inhibitor, in healthy males and patients with idiopathic pulmonary fibrosis. Maher, TM., Schlecker, C., Luedtke, D., et al.[2022]

In a study involving 13 patients with idiopathic pulmonary fibrosis (IPF), pirfenidone treatment did not significantly reduce the number of fibroblast foci, indicating that its anti-fibrotic effects may not be immediately observable in tissue samples after 6 months.

Despite the lack of significant changes in fibroblast foci and proliferation markers, the treatment was well-tolerated, and there was an increase in certain cytokines associated with angiogenesis and anti-inflammation, suggesting potential immunomodulatory effects of pirfenidone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tissue and Bronchoalveolar Lavage Biomarkers in Idiopathic Pulmonary Fibrosis Patients on Pirfenidone. Ronan, N., Bennett, DM., Khan, KA., et al.[2019]

The BI 101550 trial, a phase 2 randomized controlled trial, demonstrated positive results in improving lung function (measured by forced vital capacity) in patients with idiopathic pulmonary fibrosis (IPF) over 12 weeks, indicating its potential as an effective add-on therapy.

The RELIEF trial also showed positive outcomes for patients with progressive fibrosing interstitial lung disease (PFILD) over 48 weeks, suggesting that both trials contribute valuable insights into the evolving treatment landscape for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Add-on therapy for pulmonary fibrosis, a forthcoming era with implications for practice: the BI 101550 and RELIEF trials. Planas-Cerezales, L., Fabbri, L., Pearmain, L.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of Pirfenidone vs. Placebo in Unclassifiable Interstitial Lung Disease, by Surgical Lung Biopsy Status: Data From a post-hoc Analysis. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Pirfenidone in Unclassifiable Interstitial Lung Disease: A Subgroup Analysis by Concomitant Mycophenolate Mofetil and/or Previous Corticosteroid Use. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Plain language summary: Clinical study of BI 1015550 as a potential treatment for idiopathic pulmonary fibrosis. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Effects of nintedanib by inclusion criteria for progression of interstitial lung disease. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Systematic Review and Meta-analysis of Pirfenidone, Nintedanib, and Pamrevlumab for the Treatment of Idiopathic Pulmonary Fibrosis. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Nintedanib and immunomodulatory therapies in progressive fibrosing interstitial lung diseases. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Evaluation of the potential complication of interstitial lung disease associated with antifibrotic drugs using data from databases reporting spontaneous adverse effects. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Phase I studies of BI 1015550, a preferential phosphodiesterase 4B inhibitor, in healthy males and patients with idiopathic pulmonary fibrosis. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

[Antifibrotic therapy - new approvals for non-IPF interstitial lung diseases]. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Tissue and Bronchoalveolar Lavage Biomarkers in Idiopathic Pulmonary Fibrosis Patients on Pirfenidone. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Add-on therapy for pulmonary fibrosis, a forthcoming era with implications for practice: the BI 101550 and RELIEF trials. [2023]