BI 1015550 for Interstitial Lung Disease

No longer recruiting at 597 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the medicine BI 1015550 (Nerandomilast) benefits people with Progressive Fibrosing Interstitial Lung Diseases (PF-ILDs), a group of lung conditions that worsen over time. Participants will be divided into three groups: two groups will receive different doses of BI 1015550, and the third will receive a placebo (a pill with no active medicine). Researchers will compare lung function among the groups to assess whether the medicine improves breathing. Individuals with a doctor-confirmed diagnosis of PF-ILD, excluding Idiopathic Pulmonary Fibrosis, who possibly take nintedanib (a lung medication) without recent changes, might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that BI 1015550, also known as nerandomilast, has been tested for safety in people with lung diseases. In studies with patients who have idiopathic pulmonary fibrosis (IPF), the treatment slowed the decline in lung function compared to a placebo over 52 weeks, indicating it was generally well-tolerated during that time.

Combined data also showed a significant decrease in the risk of death for patients with IPF and another lung disease called progressive pulmonary fibrosis when using nerandomilast, which is a positive sign for safety.

However, it's important to remember that while these results are promising, each person may react differently. Regular check-ups during the trial will help monitor any unwanted effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung disease?

BI 1015550 is unique because it targets a specific enzyme called PDE4B, which plays a role in the inflammation process associated with interstitial lung disease. Traditional treatments often focus on general anti-inflammatory effects or immune suppression, but BI 1015550 directly inhibits PDE4B, potentially leading to more targeted and effective control of inflammation. Researchers are excited about this treatment because it offers a novel approach that might reduce lung damage more efficiently with fewer side effects compared to existing therapies.

What evidence suggests that BI 1015550 might be an effective treatment for PF-ILD?

Research has shown that BI 1015550, also known as nerandomilast, may help treat lung conditions like progressive pulmonary fibrosis. In this trial, participants will receive either a low or high dose of BI 1015550, or a placebo. Studies have found that BI 1015550 can slow the loss of lung function, specifically the forced vital capacity (FVC), which measures the amount of air exhaled after a deep breath. In patients with idiopathic pulmonary fibrosis (IPF), nerandomilast resulted in a smaller drop in FVC over 52 weeks compared to those who took a placebo. While most research has focused on IPF, these results suggest that BI 1015550 might also benefit other types of progressive fibrosing interstitial lung diseases. By potentially slowing the decline in lung function, this treatment could help maintain breathing ability for a longer time. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Nerandomilast 9 mg Experimental Treatment 1 Intervention

Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 9 milligrams (mg) nerandomilast, taken orally as film-coated tablets twice daily (18 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.

Group II: Nerandomilast 18 mg Experimental Treatment 1 Intervention

Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered 18 mg nerandomilast, taken orally as film-coated tablets twice daily (36 mg total), in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.

Group III: Placebo Placebo Group 1 Intervention

Patients with progressive fibrosing interstitial lung disease (PF-ILD) or progressive pulmonary fibrosis (PPF), other than idiopathic pulmonary fibrosis (IPF), were administered placebo matching nerandomilast, taken orally as film-coated tablets twice daily, in the morning and in the evening for an initial 52 weeks, followed by a variable duration till end of trial.

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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 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]

Citations

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boehringer-ingelheim.com/us/topline-results-boehringers-phase-iii-ild-study

Topline results from Boehringer's Phase III ILD study

Boehringer Ingelheim (2024) A study to find out whether BI 1015550 improves lung function in people with idiopathic pulmonary fibrosis (IPF).

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pubmed.ncbi.nlm.nih.gov

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Nerandomilast has been shown to slow the progression of idiopathic pulmonary fibrosis, but an assessment of its effects in other types of progressive pulmonary ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT05321069

NCT05321069 | A Study to Find Out Whether BI 1015550 ...

The purpose of this study is to find out whether a medicine called BI 1015550 helps people with IPF. Participants are put into 3 groups randomly, which means by ...

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nejm.org

nejm.org/doi/full/10.1056/NEJMoa2414108

Nerandomilast in Patients with Idiopathic Pulmonary Fibrosis

In patients with idiopathic pulmonary fibrosis, treatment with nerandomilast resulted in a smaller decline in the FVC than placebo over a period of 52 weeks.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12360683/

Potential of phosphodiesterase 4B inhibitors in the treatment ...

Patients with autoimmune disease-related interstitial lung disease may develop pulmonary fibrosis, which may become progressive.

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boehringer-ingelheim.com

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Nerandomilast monotherapy IPF PPF death reduction

Pooled data presented at ERS: nerandomilast monotherapy linked to nominally significant reduction in risk of death in IPF and PPF.