BI 1015550 for Idiopathic Pulmonary Fibrosis

No longer recruiting at 471 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Boehringer Ingelheim

Disqualifiers: Pulmonary abnormalities, Infections, Malignancy, 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: 13

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new medicine called BI 1015550 (Nerandomilast) to determine its effectiveness for people with Idiopathic Pulmonary Fibrosis (IPF), a lung disease that makes breathing difficult. Participants will be randomly assigned to one of three groups: two groups will receive different doses of BI 1015550, and one group will receive a placebo (a pill with no active medicine). This trial suits those diagnosed with IPF and may already be taking medications like nintedanib or pirfenidone. Participants will visit the study site regularly to monitor lung function and overall health. 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?

If you are taking nintedanib or pirfenidone for your IPF, you can continue these medications during the study. The trial does not specify about other medications, so it's best to discuss with the study team.

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

Research has shown that nerandomilast (also called BI 1015550) is generally safe for people with idiopathic pulmonary fibrosis (IPF). Studies have found that it slows the decline in lung function more effectively than a placebo over a year. This indicates that the treatment is both effective and safe for long-term use.

Additionally, the U.S. FDA has approved nerandomilast for treating IPF, confirming it has passed strict safety checks for this condition. While no treatment is without risks, this approval suggests it is safe for most patients.

Participants in earlier studies did not report any unexpected or severe side effects from nerandomilast, making it a promising option for those considering joining a clinical trial for IPF treatment. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for IPF?

Researchers are excited about nerandomilast for idiopathic pulmonary fibrosis because it offers a different approach compared to standard treatments like pirfenidone and nintedanib. Unlike these existing options, which primarily focus on slowing disease progression, nerandomilast targets inflammation through a potentially novel mechanism, which could offer better control over symptoms and disease progression. Additionally, the treatment's convenient oral administration, taken twice daily, aligns well with patient lifestyles, making it potentially easier to adhere to than some current therapies.

What evidence suggests that this trial's treatments could be effective for Idiopathic Pulmonary Fibrosis?

Research has shown that BI 1015550, also called nerandomilast, might help people with idiopathic pulmonary fibrosis (IPF). One study found that patients who took nerandomilast experienced a slower decline in lung function compared to those who took a placebo over a year, meaning their lungs stayed healthier longer. Other evidence suggests that nerandomilast might also reduce the risk of death in people with IPF. Overall, these studies indicate that nerandomilast could be a promising treatment for IPF. Participants in this trial will receive either 9 mg or 18 mg of nerandomilast, or a placebo, to further evaluate its effectiveness. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

Adults aged 40 or older with Idiopathic Pulmonary Fibrosis (IPF) can join this study. They may continue existing treatments with nintedanib or pirfenidone if stable for at least 12 weeks. Participants must have a certain level of lung function and women able to bear children must use effective birth control.

Inclusion Criteria

I have been diagnosed with Idiopathic Pulmonary Fibrosis.

I have signed and understand the consent form for this trial.

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

Exclusion Criteria

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

I tested positive for COVID-19 and haven't fully recovered in the last 4 weeks.

I haven't had, nor do I plan to have, any major surgery within 6 weeks before or 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 52 weeks

52 weeks

10 visits (in-person) during the first year

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 78 weeks

Visits every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• BI 1015550
• Placebo

Trial Overview The trial is testing BI 1015550, a new medicine for IPF, given as tablets twice daily against placebo (no active medicine). There are three groups: two different doses of BI 1015550 and one placebo group. The study lasts up to two and a half years with regular lung function tests.

How Is the Trial Designed?

Group I: Nerandomilast 9 mg BID Experimental Treatment 1 Intervention

Participants received 9 mg film-coated nerandomilast tablets orally twice daily, with doses administered at least 12 hours apart, each taken with 250 mL of water.

Group II: Nerandomilast 18 mg BID Experimental Treatment 1 Intervention

Participants received 18 mg film-coated nerandomilast tablets orally twice daily, with doses administered at least 12 hours apart, each taken with 250 mL of water.

Group III: Placebo Placebo Group 1 Intervention

Participants received placebo matching 9 mg or 18 mg nerandomilast film-coated tablets orally twice daily, with doses given at least 12 hours apart and each taken with 250 mL of water.

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 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 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 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]

The IFIGENIA trial demonstrated that N-acetylcysteine, when used alongside prednisone and azathioprine, significantly slowed the decline in lung function in patients with idiopathic pulmonary fibrosis over 12 months.

Pirfenidone is the first approved antifibrotic drug for idiopathic pulmonary fibrosis in the EU, showing efficacy in slowing lung function decline and reducing disease progression in over 1,100 patients across four clinical trials, though it may cause side effects like gastrointestinal discomfort and skin reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of pulmonary fibrosis. New substances and new interventions]. Costabel, U., Bonella, F.[2021]

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]

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]

GDC-3280, an oral medication for idiopathic pulmonary fibrosis, was found to be generally well tolerated in a phase 1 trial with 80 participants, showing no serious adverse events and mostly mild side effects like headache and nausea.

The pharmacokinetics of GDC-3280 indicated that it is effectively absorbed, with significant increases in drug exposure when taken with food, supporting its future use in clinical trials for twice-daily administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1, randomized study to evaluate safety, tolerability, and pharmacokinetics of GDC-3280, a potential novel anti-fibrotic small molecule, in healthy subjects. Cheung, D., Fong, A., Ding, HT., et al.[2021]

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]

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]

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. 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 ...

3. boehringer-ingelheim.com boehringer-ingelheim.com/us/human-health/topline-results-boehringers-phase-iii-ipf-study

Topline results from Boehringer's Phase III IPF Study Press release announcing topline results of Boehringer Ingelheim's Phase III FIBRONEER-IPF study in indiopathic pulmonary fibrosis.

4. 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.

5. 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 ...

6. boehringer-ingelheim.com boehringer-ingelheim.com/human-health/lung-diseases/pulmonary-fibrosis/fda-approves-jascayd-nerandomilast-first-new-treatment-ipf-over-decade

FDA approves JASCAYD® (nerandomilast) as first new ... U.S. FDA approves Boehringer's JASCAYD® (nerandomilast tablets) as first new treatment option for adults with IPF in over a decade.

7. 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 ...