BI 1839100 for Pulmonary Fibrosis

Recruiting at 200 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Boehringer Ingelheim

Must be taking: Nintedanib, Pirfenidone, Immunomodulatory

Disqualifiers: Acute exacerbation, Reversible airflow, Chronic infection, others

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

Compensation: Varies

Number of Visits: 8

Duration: 12 weeks

230 Participants Needed

Trial Summary

What is the purpose of this trial?

Adults 40 years of age and older with idiopathic pulmonary fibrosis (IPF) or 18 years and older with progressive pulmonary fibrosis (PPF) can participate in this study. Only people who have a chronic cough can take part. The purpose of this study is to find out how well BI 1839100 helps reduce coughing in people with IPF or PPF. Participants who have IPF are put into 4 groups by chance. Participants in 3 groups get different doses of BI 1839100. Participants in 1 group get placebo. Placebo looks like BI 1839100 but does not contain any medicine. Participants take the treatment for 3 months. After 1 month of treatment, participants who take the highest dose will have coughing measured to find out if the medicine works. If it does not work, the study may be stopped. Participants who have IPF are in the study for slightly longer than 4 months. During this time, they visit the study site 7 times. This study will also measure the effects of BI 1839100 on coughing and lung function in a smaller group of people with PPF. During the study, coughing is measured over 24 hours about once per month using a portable device given to participants to use during the study. Participants fill in questionnaires about their coughing. Doctors also perform breathing tests that measure how well the lungs are working at the site visits. Researchers compare the results between participants who take BI 1839100 and placebo. The doctors also regularly check participants' health and take note of any unwanted effects.

Will I have to stop taking my current medications?

If you are taking nintedanib or pirfenidone, you can continue these medications as long as you have been on a stable dose for at least 12 weeks before starting the trial and plan to stay on them throughout the trial. If you are not on these medications, you should not start or restart them during the trial. For PPF, if you are on immunomodulatory therapy like tacrolimus, mycophenolate mofetil, or azathioprine, you can continue if the dose has been stable for 12 weeks before the trial.

How is the drug BI 1839100 different from other treatments for pulmonary fibrosis?

BI 1839100 is unique because it targets specific growth factor receptors involved in the development of pulmonary fibrosis, potentially slowing disease progression by inhibiting pathways that lead to lung scarring. This approach is different from other treatments that may not specifically target these pathways. ^{1 2 3 4 5}

Eligibility Criteria

Adults aged 40+ with idiopathic pulmonary fibrosis (IPF) or those aged 18+ with progressive pulmonary fibrosis (PPF), who have a chronic cough, can join this study. They must not be on certain lung fibrosis treatments for at least 12 weeks before the trial and should not plan to start them during the trial. Their lungs must function at a minimum level.

Inclusion Criteria

I have been diagnosed with idiopathic pulmonary fibrosis.

I have a chronic cough for over 8 weeks due to IPF, not improved by treatments.

I am at least 40 years old.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive BI 1839100 or placebo for 12 weeks. Coughing is measured monthly, and questionnaires and breathing tests are conducted.

12 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BI 1839100

Trial Overview The study tests if BI 1839100 reduces cough in IPF or PPF patients compared to a placebo. Participants are randomly assigned to receive different doses of BI 1839100 or placebo for three months, with their coughing measured using a portable device and through questionnaires.

Participant Groups

Group I: Phase IIb, PPF cohort: BI 1839100 high dose Experimental Treatment 1 Intervention

Group II: Phase IIa/IIb, IPF cohort: BI 1839100 medium dose Experimental Treatment 1 Intervention

Group III: Phase IIa/IIb, IPF cohort: BI 1839100 low dose Experimental Treatment 1 Intervention

Group IV: Phase IIa/IIb, IPF cohort: BI 1839100 high dose Experimental Treatment 1 Intervention

Group V: Phase IIb, PPF cohort: Placebo Placebo Group 1 Intervention

Group VI: Phase IIa/IIb, IPF cohort: 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

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 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]

BIBF 1000 effectively reduced lung fibrosis in a rat model by decreasing collagen deposition and inhibiting pro-fibrotic gene expression, indicating its potential as an anti-fibrotic treatment.

In ex vivo assays, BIBF 1000 demonstrated dose-dependent inhibition of fibroblast differentiation driven by TGF-beta, outperforming imatinib mesylate, suggesting it could be a promising new therapy for idiopathic pulmonary fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of PDGF, VEGF and FGF signalling attenuates fibrosis. Chaudhary, NI., Roth, GJ., Hilberg, F., et al.[2023]

Idiopathic pulmonary fibrosis is a serious disease with limited treatment options, and it involves complex interactions among various proinflammatory and profibrogenetic growth factors.

BIBF 1120, a potent triple blocker of these growth factor receptors, has shown promise in preclinical and clinical studies by delaying disease progression and improving outcomes for patients with idiopathic pulmonary fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nintedanib (BIBF 1120) for IPF: a tomorrow therapy? Antoniu, SA.[2021]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

No effect of pirfenidone treatment in fulminant bleomycin-induced pneumonitis. [2020]

2. England pubmed.ncbi.nlm.nih.gov

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

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

Inhibition of PDGF, VEGF and FGF signalling attenuates fibrosis. [2023]

4. Italy pubmed.ncbi.nlm.nih.gov

Nintedanib (BIBF 1120) for IPF: a tomorrow therapy? [2021]

5. 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]