BI 1015550 for Pulmonary Fibrosis

(FIBRONEER™-ON Trial)

Recruiting at 451 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Boehringer Ingelheim

Must be taking: Nerandomilast

Disqualifiers: Suicidality, Severe depression, Malignant neoplasm, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: Unknown

Duration: 22 months

1700 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess how well people with pulmonary fibrosis (a lung disease that causes scarring and breathing issues) can tolerate long-term treatment with nerandomilast (also known as BI 1015550). Researchers seek to determine if this treatment can improve lung function and slow disease progression. Participants will take nerandomilast in tablet form for nearly two years while continuing their usual treatments. Eligible participants should have already completed a previous study with nerandomilast. Regular doctor visits will include health check-ups and lung function tests. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially bringing a new treatment to market.

Will I have to stop taking my current medications?

The trial allows participants to continue their regular treatment for pulmonary fibrosis during the study. However, if you are taking any restricted medications or drugs that might interfere with the trial, you may need to stop those. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that nerandomilast is likely to be safe for humans?

Research has shown that nerandomilast is promising in terms of safety for patients with idiopathic pulmonary fibrosis (IPF). In earlier studies, patients who took nerandomilast experienced a slower decline in lung function over a year compared to those on a placebo, indicating that the treatment is generally well-tolerated. Combined study results suggest that nerandomilast may lower the risk of death in people with IPF and progressive pulmonary fibrosis (PPF).

Another study examined nerandomilast's safety and found it generally safe, even for participants with varying liver function levels. This supports the idea that nerandomilast is well-tolerated and safe for long-term use. While side effects may occur, current data indicates that nerandomilast is considered safe for people with conditions like IPF and PPF. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for pulmonary fibrosis, which typically include options like pirfenidone and nintedanib that mainly slow disease progression, BI 1015550 offers a fresh approach by targeting a different mechanism. Researchers are excited about BI 1015550 because it is a novel PDE4B inhibitor, which could potentially reduce inflammation more effectively and halt lung scarring. This new mechanism of action might allow BI 1015550 to tackle the underlying processes of pulmonary fibrosis more directly, offering hope for better outcomes for patients.

What evidence suggests that nerandomilast might be an effective treatment for pulmonary fibrosis?

Research has shown that nerandomilast, also known as BI 1015550, might help slow the decline of lung function in people with pulmonary fibrosis. In a study involving patients with idiopathic pulmonary fibrosis (IPF), those who took nerandomilast experienced a smaller decrease in lung capacity (measured as Forced Vital Capacity, or FVC) over a year compared to those on a placebo. Additionally, evidence suggests that this treatment could reduce the risk of death in individuals with both IPF and progressive pulmonary fibrosis (PPF). Early results are promising, indicating that nerandomilast may slow disease progression. Overall, these findings support the potential of nerandomilast as an effective option for managing pulmonary fibrosis. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for people with idiopathic or progressive pulmonary fibrosis who completed a previous study (1305-0014 or 1305-0023) without dropping out early. They must consent to the study's rules and, if they can have children, agree to use effective birth control during the trial.

Inclusion Criteria

I finished treatment in trials 1305-0014 or 1305-0023 without stopping early, even if there were short breaks.

I have signed and dated the consent form according to guidelines before joining the trial.

I am using or willing to use effective birth control if I can have children.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take nerandomilast as tablets for up to 1 year and 10 months

22 months

Regular visits to doctors

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BI 1015550

Trial Overview The trial tests long-term tolerance of BI 1015550 in patients with pulmonary fibrosis. It aims to see if this drug improves lung function and delays worsening symptoms, hospital visits, or death. Participants take BI 1015550 tablets alongside their usual treatments for up to one year and ten months.

How Is the Trial Designed?

Group I: BI 1015550 treatment group Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

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]

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]

A comprehensive safety analysis of pirfenidone, involving 789 patients over a median exposure of 2.6 years, shows that it is generally safe and well tolerated for treating idiopathic pulmonary fibrosis (IPF).

The most common side effects were mild to moderate gastrointestinal and skin-related events, with serious liver enzyme elevations occurring in only 2.7% of patients, indicating a low risk of severe adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive assessment of the long-term safety of pirfenidone in patients with idiopathic pulmonary fibrosis. Valeyre, D., Albera, C., Bradford, WZ., 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]

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 a study of 92 patients with idiopathic pulmonary fibrosis (IPF) receiving pirfenidone, the drug showed an acceptable safety profile, with skin-related (25%) and gastrointestinal (17.5%) adverse events being the most common, leading to discontinuation in 22.5% of cases.

Despite some patients experiencing significant improvements in lung function, the overall decline in lung function (%FVC and %DLCO) was noted over 36 months, highlighting the need for further research through prospective observational registries to better understand pirfenidone's long-term efficacy in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal "Real-World" Outcomes of Pirfenidone in Idiopathic Pulmonary Fibrosis in Greece. Tzouvelekis, A., Karampitsakos, T., Ntolios, P., et al.[2022]

Pirfenidone, an antifibrotic drug, was used in combination with steroids to treat two human cases of bleomycin-induced pneumonitis (BIP), but unfortunately, both patients died, suggesting that the treatment may have been initiated too late.

The findings highlight the need for further research into early or preventive use of pirfenidone during bleomycin-containing chemotherapy to potentially improve outcomes for patients at risk of developing BIP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No effect of pirfenidone treatment in fulminant bleomycin-induced pneumonitis. Bendstrup, E., Hyldgaard, C., Agerbæk, M., et al.[2020]

In a study of 281 patients with idiopathic pulmonary fibrosis (IPF) treated with either pirfenidone or nintedanib, both drugs were found to be safe and well-tolerated, confirming their safety profiles in real-world settings.

Nintedanib was associated with a lower rate of permanent treatment discontinuation (8.3%) compared to pirfenidone (18.3%), and adverse events from nintedanib were generally easier to manage, indicating it may be a more favorable option for long-term treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety of Antifibrotic Drugs in IPF: A Real-World Experience. Levra, S., Guida, G., Sprio, AE., et al.[2022]

In a study of 261 patients with idiopathic pulmonary fibrosis (IPF), those treated with pirfenidone had a significantly lower discontinuation rate due to adverse events compared to those treated with nintedanib (37% vs. 76% within one year).

Despite similar overall survival rates and treatment continuity, the higher rate of discontinuation due to adverse events in the nintedanib group suggests that managing these side effects is crucial for maintaining long-term antifibrotic therapy in IPF patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential Discontinuation Profiles between Pirfenidone and Nintedanib in Patients with Idiopathic Pulmonary Fibrosis. Takehara, K., Koga, Y., Hachisu, Y., et al.[2022]

Citations

1. 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.

2. boehringer-ingelheim.com boehringer-ingelheim.com/human-health/lung-diseases/pulmonary-fibrosis/nerandomilast-monotherapy-ipf-ppf-death-reduction

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.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40388329/

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

4. 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 ...

5. the-innovation.org the-innovation.org/data/article/medicine/preview/pdf/XINNMEDICINE-2025-0078.pdf

Nerandomilast shatters decade-long stalemate in fibrotic lung ... Boehringer Ingelheim announced that its oral anti-fibrotic drug, nerandomilast (BI 1015550), yielded significant and promising results in the ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40387033/

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 ...

7. atsjournals.org atsjournals.org/doi/abs/10.1164/ajrccm.2025.211.Abstracts.A1765

Pharmacokinetics, Safety, And Tolerability Of A Single Oral ... The objective of this trial was to investigate the effect of mild and moderate HI on the pharmacokinetics (PK), safety, and tolerability of nerandomilast.