BMS-986278 for Idiopathic Pulmonary Fibrosis

Recruiting at 844 trial locations

Overseen By BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Bristol-Myers Squibb

Must be taking: Pirfenidone, Nintedanib

Disqualifiers: Stroke, Heart failure, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

1185 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy, safety, and tolerability of BMS-986278 in participants with Idiopathic Pulmonary Fibrosis.

Will I have to stop taking my current medications?

If you are taking pirfenidone or nintedanib, you must have been on a stable dose for at least 90 days before joining the trial. If you are not taking these medications, you should not have taken them in the 28 days before the trial starts.

What data supports the effectiveness of the drug BMS-986278 for idiopathic pulmonary fibrosis?

The study on BMS-986020, a similar drug, showed that it slowed the decline in lung function compared to a placebo in patients with idiopathic pulmonary fibrosis, suggesting potential effectiveness for BMS-986278 as well. ^{1 2 3 4 5}

What is known about the safety of BMS-986278 for human use?

There is no specific safety data available for BMS-986278, but its predecessor, BMS-986020, was generally well-tolerated in a phase 2 trial for idiopathic pulmonary fibrosis, with treatment discontinuation due to adverse events being common in antifibrotic treatments. ^{3 6 7 8 9}

What makes the drug BMS-986278 unique for treating idiopathic pulmonary fibrosis?

BMS-986278 is a novel treatment for idiopathic pulmonary fibrosis, distinct from existing options like pirfenidone, as it is being evaluated for its unique mechanism of action and potential to improve upon the limitations of current anti-fibrotic treatments. ^{1 2 3 4 5}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for adults over 40 with Idiopathic Pulmonary Fibrosis diagnosed within the last 7 years, confirmed by specific chest scans. Participants must use effective contraception if of childbearing potential and can't join if they've had a stroke or certain cancers recently, or significant heart disease as assessed by the investigator.

Inclusion Criteria

I was diagnosed with IPF within the last 7 years, confirmed by a chest HRCT scan.

I am 40 years or older with idiopathic pulmonary fibrosis.

I haven't taken pirfenidone or nintedanib in the last 28 days.

Exclusion Criteria

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

I have not had a stroke or mini-stroke in the last 3 months.

I haven't had serious heart problems in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BMS-986278 or placebo to evaluate efficacy, safety, and tolerability

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

28 days

Long-term Follow-up

Participants are monitored for long-term outcomes such as disease progression and mortality

Up to approximately 3 years

Treatment Details

Interventions

• BMS-986278

Trial Overview The study tests BMS-986278's effectiveness and safety in treating Idiopathic Pulmonary Fibrosis compared to a placebo. Some participants will receive BMS-986278 while others will get a placebo, without knowing which one they're getting.

Participant Groups

Group I: BMS-986278 Dose 2 Experimental Treatment 1 Intervention

Group II: BMS-986278 Dose 1 Experimental Treatment 1 Intervention

Group III: BMS-986278 Placebo Placebo Group 1 Intervention

BMS-986278 is already approved in United States for the following indications:

Approved in United States as BMS-986278 for:

• Progressive Pulmonary Fibrosis (Breakthrough Therapy Designation)

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Findings from Research

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]

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]

External controls (ECs) derived from historical randomized clinical trials (RCTs) showed comparable treatment effects to the original BMS-986020 trial for idiopathic pulmonary fibrosis (IPF), indicating their potential utility in enhancing trial efficiency.

In contrast, ECs from real-world data sources, such as registries and electronic health records, demonstrated a slower rate of lung function decline compared to the placebo group, suggesting they may not provide reliable comparability for evaluating new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External Control Arms in Idiopathic Pulmonary Fibrosis Using Clinical Trial and Real-World Data Sources. Swaminathan, AC., Snyder, LD., Hong, H., et al.[2023]

In a study using C57BL/6 male mice, the NO-releasing compound KMUP-1 significantly reduced inflammation and fibrosis in the lungs caused by bleomycin, as evidenced by decreased neutrophil counts and lower levels of inflammatory markers in bronchoalveolar lavage fluid.

KMUP-1S, which is bonded with simvastatin, showed enhanced effects in preventing lung fibrosis by inhibiting key signaling pathways and collagen deposition, suggesting it could be a promising treatment for pulmonary fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NO-releasing xanthine KMUP-1 bonded by simvastatin attenuates bleomycin-induced lung inflammation and delayed fibrosis. Liu, CP., Kuo, MS., Wu, BN., 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]

BMS-986278, a second-generation LPA1 antagonist, is being tested in a phase 2 trial for its efficacy in treating idiopathic pulmonary fibrosis (IPF) and progressive fibrotic interstitial lung diseases (PF-ILD), with 360 participants enrolled across both conditions.

The primary goal of the trial is to measure the change in lung function (forced vital capacity) over 26 weeks, comparing the effects of two doses of BMS-986278 against a placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 trial design of BMS-986278, a lysophosphatidic acid receptor 1 (LPA1) antagonist, in patients with idiopathic pulmonary fibrosis (IPF) or progressive fibrotic interstitial lung disease (PF-ILD). Corte, TJ., Lancaster, L., Swigris, JJ., et al.[2022]

LYT-100 (deupirfenidone) was found to be well tolerated in a phase 1b study with 1000 mg doses administered twice daily, showing only mild and transient adverse events, which suggests a potentially safer profile compared to existing antifibrotic treatments.

The pharmacokinetic profile of LYT-100 demonstrated dose-proportionality and a higher ratio of the parent drug to its metabolite compared to pirfenidone, indicating that deuteration may positively influence its metabolism and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase 1 Evaluation of Deupirfenidone, a Novel Deuterium-Containing Drug Candidate for Interstitial Lung Disease and Other Inflammatory and Fibrotic Diseases. Chen, MC., Korth, CC., Harnett, MD., et al.[2022]

In a phase 2 trial involving 140 patients with idiopathic pulmonary fibrosis (IPF), the LPA1 antagonist BMS-986020 significantly reduced the decline in lung function (measured by forced vital capacity) over 26 weeks compared to placebo, indicating its potential efficacy in treating IPF.

BMS-986020 treatment led to significant reductions in serum levels of extracellular matrix (ECM)-neoepitope biomarkers associated with IPF prognosis, and in vitro studies showed that it effectively inhibited LPA1-induced fibrogenesis, revealing a novel antifibrotic mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LPA1 antagonist BMS-986020 changes collagen dynamics and exerts antifibrotic effects in vitro and in patients with idiopathic pulmonary fibrosis. Decato, BE., Leeming, DJ., Sand, JMB., et al.[2022]

In a phase 2 study involving 143 patients with idiopathic pulmonary fibrosis (IPF), the high-affinity LPA1 antagonist BMS-986020 significantly slowed the decline in lung function (FVC) compared to placebo over 26 weeks, particularly in the group receiving the drug twice daily.

However, the treatment was associated with dose-related increases in liver enzymes and led to the early termination of the study due to three cases of cholecystitis linked to the drug, highlighting potential safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial of BMS-986020, a Lysophosphatidic Acid Receptor Antagonist for the Treatment of Idiopathic Pulmonary Fibrosis. Palmer, SM., Snyder, L., Todd, JL., et al.[2019]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Longitudinal "Real-World" Outcomes of Pirfenidone in Idiopathic Pulmonary Fibrosis in Greece. [2022]

2. England 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. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

External Control Arms in Idiopathic Pulmonary Fibrosis Using Clinical Trial and Real-World Data Sources. [2023]

4. England pubmed.ncbi.nlm.nih.gov

NO-releasing xanthine KMUP-1 bonded by simvastatin attenuates bleomycin-induced lung inflammation and delayed fibrosis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

Phase 2 trial design of BMS-986278, a lysophosphatidic acid receptor 1 (LPA1) antagonist, in patients with idiopathic pulmonary fibrosis (IPF) or progressive fibrotic interstitial lung disease (PF-ILD). [2022]

7. United States pubmed.ncbi.nlm.nih.gov

A Randomized Phase 1 Evaluation of Deupirfenidone, a Novel Deuterium-Containing Drug Candidate for Interstitial Lung Disease and Other Inflammatory and Fibrotic Diseases. [2022]

8. England pubmed.ncbi.nlm.nih.gov

LPA1 antagonist BMS-986020 changes collagen dynamics and exerts antifibrotic effects in vitro and in patients with idiopathic pulmonary fibrosis. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial of BMS-986020, a Lysophosphatidic Acid Receptor Antagonist for the Treatment of Idiopathic Pulmonary Fibrosis. [2019]