Bexotegrast for Idiopathic Pulmonary Fibrosis

No longer recruiting at 334 trial locations

Overseen By Eric Lefebvre

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Pliant Therapeutics, Inc.

Must not be taking: Pulmonary hypertension drugs

Disqualifiers: Smoking, Recent malignancy, Hepatic impairment, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called bexotegrast (also known as PLN-74809) for individuals with idiopathic pulmonary fibrosis (IPF), a lung disease that causes scarring and breathing problems. Researchers aim to assess the safety and effectiveness of bexotegrast by comparing different doses to a placebo (a substance with no active medicine). Individuals diagnosed with IPF in the last seven years and who have stable lung function might be suitable for this study. Participants can either be on a stable IPF treatment plan or have not taken IPF treatment for a while. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in IPF treatment.

Do I have to stop taking my current medications for this trial?

The trial does not specify that you must stop taking your current medications. If you are on treatment for IPF, you can continue if it's been stable for at least 12 weeks before screening. If you are not currently on IPF treatment, you must not have taken any for at least 8 weeks before screening.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, if you are currently on treatment for idiopathic pulmonary fibrosis (IPF), you can continue if the dose has been stable for at least 12 weeks before screening. If you are not on treatment, you must not have taken any IPF therapy for at least 8 weeks before screening.

Is there any evidence suggesting that bexotegrast (PLN-74809) is likely to be safe for humans?

Research has shown that bexotegrast is generally safe and well-tolerated in people with idiopathic pulmonary fibrosis (IPF). One study observed 88 participants over 12 weeks, yielding positive results. Most participants did not experience serious side effects. Another report found that this treatment was generally well-tolerated by people with IPF. While these findings are promising, everyone may react differently. Discuss any concerns with a healthcare provider before deciding to join a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for idiopathic pulmonary fibrosis?

Unlike the standard treatments for idiopathic pulmonary fibrosis (IPF), which mainly include antifibrotic medications like nintedanib and pirfenidone, Bexotegrast (PLN-74809) offers a novel approach by targeting integrin proteins that are involved in the fibrotic process. Researchers are excited about Bexotegrast because it specifically inhibits these integrins, potentially slowing or halting the progression of fibrosis more effectively than current options. This mechanism is distinct from existing treatments and could lead to better outcomes for patients with IPF.

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

Research shows that bexotegrast may help treat idiopathic pulmonary fibrosis, a lung disease that causes scarring and makes breathing difficult. In earlier studies, patients who took bexotegrast showed noticeable improvement in lung function, measured by forced vital capacity (FVC), over 4, 8, and 12 weeks compared to those on lower doses. This trial will test different doses of bexotegrast, specifically 160 mg and 320 mg, to evaluate its potential to increase lung capacity. Additionally, early data indicated it could reduce lung scarring. These findings suggest that bexotegrast might effectively slow the disease's progression. ^{3 6 7 8 9}

Who Is on the Research Team?

Pliant Therapeutics Medical Monitor

Principal Investigator

Pliant Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for adults over 40 with idiopathic pulmonary fibrosis diagnosed within the last 7 years, having certain lung function levels. Stable patients on IPF treatments or those not treated for at least 8 weeks can join. Exclusions include smokers, liver/kidney disease sufferers, recent cancer patients (except some skin/cervical cancers), pregnant/breastfeeding women, and those on unapproved fibrosis drugs.

Inclusion Criteria

I was diagnosed with IPF less than 7 years ago.

I have been on a stable treatment for IPF for at least 12 weeks.

I haven't taken any IPF treatments for at least 8 weeks.

Exclusion Criteria

I have not had cancer, except for certain skin or cervical cancers, in the last 5 years.

I have previously been treated with bexotegrast.

I might get a lung transplant during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

5 weeks

Treatment

Participants receive either 160 mg or 320 mg of bexotegrast or placebo for 52 weeks

52 weeks

Safety Follow-up

Participants are monitored for safety after the treatment period

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bexotegrast (PLN-74809)

Trial Overview The BEACON-IPF study tests bexotegrast (PLN-74809) against a placebo to see if it's safe and effective for treating idiopathic pulmonary fibrosis. Participants are randomly assigned to receive either the drug or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: Placebo Experimental Treatment 1 Intervention

Placebo

Group II: Bexotegrast (PLN-74809) 320 mg Dose Experimental Treatment 1 Intervention

Bexotegrast (PLN-74809) 320 mg Dose - 52 weeks

Group III: Bexotegrast (PLN-74809) 160 mg Dose Experimental Treatment 1 Intervention

Bexotegrast (PLN-74809) 160 mg Dose - 52 weeks

Who Is Running the Clinical Trial?

Pliant Therapeutics, Inc.

Lead Sponsor

Trials

8

Recruited

720+

Published Research Related to This Trial

PDE4 inhibitors, such as roflumilast and cilomilast, significantly improve lung function in COPD patients, with an average increase in forced expiratory volume (FEV1) of 51.53 mL compared to placebo, based on 34 trials involving over 20,000 participants.

While PDE4 inhibitors reduce the likelihood of COPD exacerbations, they are associated with gastrointestinal side effects and weight loss, indicating that they should be used cautiously, particularly as add-on therapy for patients with persistent symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease. Chong, J., Leung, B., Poole, P.[2022]

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]

The updated guidelines for treating idiopathic pulmonary fibrosis (IPF) strongly recommend antifibrotic drugs nintedanib and pirfenidone as effective treatments, based on high-quality evidence from recent trials.

Several previously considered treatments, including triple therapy with prednisolone, azathioprine, and acetyl-cysteine, as well as imatinib and various endothelin receptor antagonists, were deemed unsuitable for IPF patients, highlighting the need for careful selection of therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

German Guideline for Idiopathic Pulmonary Fibrosis - Update on Pharmacological Therapies 2017. Behr, J., Günther, A., Bonella, F., et al.[2019]

The phase III trial (FIBRONEER-IPF) is investigating the efficacy of BI 1015550, a phosphodiesterase 4B inhibitor, in preventing decline in lung function (measured by forced vital capacity) in patients with idiopathic pulmonary fibrosis (IPF) over at least 52 weeks.

The study is designed to compare two doses of BI 1015550 (9 mg and 18 mg) against a placebo, with a primary focus on lung function change and secondary outcomes including acute exacerbations, hospitalizations, or death, ensuring a comprehensive assessment of the drug's impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of a phase III, double-blind, randomised, placebo-controlled trial of BI 1015550 in patients with idiopathic pulmonary fibrosis (FIBRONEER-IPF). 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]

The updated guidelines for idiopathic pulmonary fibrosis (IPF) strongly recommend the use of antifibrotic drugs nintedanib and pirfenidone, which have shown significant efficacy in treating the disease, based on high-quality evidence from clinical trials.

Several previously considered treatments, including triple therapy with prednisolone, azathioprine, and acetyl-cysteine, as well as imatinib and various endothelin receptor antagonists, were deemed unsuitable for IPF patients, highlighting the need for careful selection of therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[German Guideline for Idiopathic Pulmonary Fibrosis - Update on Pharmacological Therapies 2017]. Behr, J., Günther, A., Bonella, F., et al.[2019]

A new classification of chronic obstructive pulmonary disease (COPD) now considers airflow limitation alongside symptoms and exacerbation rates, indicating a shift in how the disease is understood and treated.

Roflumilast has been approved as a treatment that effectively reduces the frequency of exacerbations in patients with chronic bronchitis and severe airflow obstruction, while procalcitonin levels can help guide antibiotic use during acute exacerbations, leading to better outcomes with less antibiotic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chronic obstructive pulmonary disease : new pharmacotherapeutic options]. Greulich, T., Koczulla, AR., Vogelmeier, C.[2021]

In the Phase III ETHOS study involving 8509 patients with moderate-to-very-severe COPD, the triple therapy of budesonide/glycopyrronium/formoterol (BGF) significantly reduced moderate/severe exacerbation rates by 24% in patients with prior ICS use and 23% in those without, compared to dual therapy with glycopyrronium/formoterol (GFF).

The benefits of BGF in improving symptoms, health-related quality of life, and lung function were consistent regardless of whether patients had used inhaled corticosteroids (ICS) in the 30 days prior to the study, indicating the therapy's broad efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between prior inhaled corticosteroid use and benefits ofbudesonide/glycopyrronium/formoterol fumarate dihydrate on exacerbations, symptoms, health-related quality of life, and lung function in patients with chronic obstructive pulmonary disease: Analyses from the ETHOS study. Singh, D., Rabe, KF., Martinez, FJ., et al.[2022]

Roflumilast, a phosphodiesterase-4 (PDE4) inhibitor, has been shown to significantly improve lung function and reduce exacerbations in patients with severe COPD (FEV1 <50% predicted), making it an effective add-on therapy to long-acting bronchodilators.

While common side effects like headache and diarrhea may occur, they are usually transient and not serious, indicating that roflumilast is generally safe for use in the targeted patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of roflumilast in COPD: a primary care perspective. Price, D., Chisholm, A., Ryan, D., et al.[2021]

In a 6-month study involving 661 asthma patients not well controlled by low-dose inhaled corticosteroids, the NEXThaler device delivering extrafine beclometasone dipropionate/formoterol showed a high satisfaction rate of 96.3% among users.

The treatment significantly improved asthma control, with the percentage of patients with uncontrolled asthma dropping from 79.1% to 6.7%, alongside enhancements in lung function and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extrafine Beclometasone Dipropionate/Formoterol NEXThaler on Device Usability, Adherence, Asthma Control and Quality of Life. A Panhellenic Prospective, Non-Interventional Observational Study in Patients with Asthma-The NEXT-Step Study. Bakakos, P., Chatziapostolou, P., Katerelos, P., et al.[2022]

BI 1015550, an oral PDE4B inhibitor, has shown promise in stabilizing lung function in patients with idiopathic pulmonary fibrosis (IPF) over a 12-week period, demonstrating the largest effect size for an investigational drug in a phase 2 trial.

The treatment was well-tolerated and had an acceptable safety profile, leading to the initiation of a phase 3 trial to further evaluate its efficacy and safety in IPF patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BI 1015550: an investigational phosphodiesterase 4B (PDE4B) inhibitor for lung function decline in idiopathic pulmonary fibrosis (IPF). Sgalla, G., Simonetti, J., Cortese, S., et al.[2023]

A safety analysis of ubrogepant and rimegepant, based on 2010 and 3691 adverse event reports respectively, identified 10 and 25 significant safety signals, indicating potential risks associated with these medications.

The adverse events reported were primarily related to psychiatric, neurological, gastrointestinal, skin, vascular, and infectious issues, highlighting the need for further research to confirm these safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ubrogepant and rimegepant: signal detection using spontaneous reports of adverse events from the Food and Drug Administration Adverse Event Reporting System. Battini, V., Carnovale, C., Clementi, E., et al.[2023]

In a real-world study of patients with Idiopathic Pulmonary Fibrosis (IPF), both pirfenidone and nintedanib were found to have common side effects, primarily gastrointestinal, but these were manageable in most cases.

Despite treating older patients with more severe disease and additional health issues, the discontinuation rates due to side effects were similar to those observed in clinical trials, supporting the safety and efficacy of these treatments in broader patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real World Experiences: Pirfenidone and Nintedanib are Effective and Well Tolerated Treatments for Idiopathic Pulmonary Fibrosis. Hughes, G., Toellner, H., Morris, H., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38843105/

Bexotegrast in Patients with Idiopathic Pulmonary Fibrosis Exploratory efficacy endpoints included change from baseline in FVC, quantitative lung fibrosis (QLF) extent (%), and changes from baseline in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04396756

NCT04396756 | Evaluation of Efficacy and Safety of PLN- ... A Phase 2a, multicenter, 4-part, randomized, double-blind, dose-ranging, placebo-controlled study to evaluate the safety, tolerability, and PK of once-daily ...

3. ir.pliantrx.com ir.pliantrx.com/news-releases/news-release-details/pliant-therapeutics-announces-positive-data-integris-ipf-phase

Press Release Bexotegrast demonstrated statistically significant increase in FVC at 4, 8 and 12 weeks of treatment, outperforming lower dose groups.

4. atsjournals.org atsjournals.org/doi/full/10.1164/rccm.202403-0636OC

Bexotegrast in Patients with Idiopathic Pulmonary Fibrosis The exploratory efficacy and biomarker data presented here provide the first evidence of the potential effect of bexotegrast in participants ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06097260

NCT06097260 | Randomized, Double-blind Study of ... This is a randomized, double-blind, dose-ranging, placebo-controlled study to evaluate the efficacy and safety of 2 doses of bexotegrast (PLN-74809) [160 ...

6. pliantrx.com pliantrx.com/wp-content/uploads/2024/09/Pliant-Therapeutics-ERS-2024-Bexotegrast-Overall-Safety-Oral-Presentation.pdf

Safety and tolerability of bexotegrast in Phase 2 trials of ... Late-stage evaluation of bexotegrast in participants with IPF is currently underway (BEACON-IPF; NCT06097260). IPF, idiopathic pulmonary fibrosis; TEAE, ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11351797/

Bexotegrast in Patients with Idiopathic Pulmonary Fibrosis Data available for 88 participants. Safety and Tolerability through Week 12. Overall, bexotegrast demonstrated a favorable safety and tolerability profile over ...

8. pliantrx.com pliantrx.com/wp-content/uploads/2024/05/Pliant-ATS-2024-Oral-INTEGRIS-IPF-PSC-Safety-Update.pdf

Dual αVβ6/αVβ1 integrin inhibitor Bexotegrast (PLN-74809 ... IPF, idiopathic pulmonary fibrosis; PSC, primary sclerosing cholangitis; TEAE, treatment-emergent adverse event. Bexotegrast was well tolerated ...

9. atsjournals.org atsjournals.org/doi/abs/10.1164/rccm.202403-0636OC

Bexotegrast in Patients with Idiopathic Pulmonary Fibrosis Conclusions: Bexotegrast demonstrated a favorable safety and tolerability profile, up to 12 weeks for the doses studied. Exploratory analyses ...