A Study to Evaluate the Efficacy, Safety, and Tolerability of BMS-986278 in Participants With Progressive Pulmonary Fibrosis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy, safety, and tolerability of BMS-986278 in Participants with Progressive Pulmonary Fibrosis.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Efficacy, Safety, and Tolerability of BMS-986278 in Participants With Progressive Pulmonary Fibrosis

Conditions
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Progressive Pulmonary Fibrosis

Intervention / Treatment
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* Drug: BMS-986278
* Drug: BMS-986278 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of interstitial lung disease (ILD) with features consistent with progressive ILD within 24 months prior to screening, and ≥ 10% extent of disease on screening high-resolution computed tomography (HRCT).. If on pirfenidone or nintedanib, participants must have been on a stable dose for at least 90 days prior to screening If not currently on pirfenidone or nintedanib, participants must not have received either of these medications within 28 days prior to screening. Mycophenolate mofetil (MMF), mycophenolic acid (MA), azathioprine (AZA), and Tacrolimus are permitted provided that the participant is on a stable dose for at least 90 days prior to screening. If not currently on MMF, MA, AZA, or tacrolimus, participants must not have taken these medications within 28 days prior to screening. Traditional disease-modifying antirheumatic drug (DMARDs) (eg. Methotrexate, leflunomide, sulfasalazine, or hydroxychloroquine), Biologic DMARDs (eg. TNF blockers and IL-1 inhibitors) and Janus kinase inhibitors (JAK inhibitors) (eg. tofacitinib, upadacitinib) are permitted provided that the participant is on a stable dose for at least 90 days prior to screening. Systemic corticosteroids are permitted provided that the participant is on prednisone ≤ 15 mg/day or equivalent for at least 70 days prior to Day 1. Women who are of childbearing potential must have a highly effective form of contraception and must provide a negative urine/serum pregnancy test Men who are sexually active with women of childbearing potential agree to use male barrier contraception Exclusion Criteria: Idiopathic pulmonary fibrosis with usual interstitial pneumonia (UIP) verification at screening History of stroke or transient ischemic attack within 3 months prior to screening Significant cardiac disease within 6 months prior to screening per the investigator's discretion Participants who have a current malignancy or a previous malignancy in the past 5 years prior to screening, except for those who have a documented history of cured nonmetastatic squamous cell skin carcinoma, basal cell skin carcinoma, or cervical carcinoma in situ. Note: Other protocol-defined inclusion/exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BMS-986278 Dose 1<br> | Drug: BMS-986278<br>* Specified dose on specified days<br>|
| Experimental: BMS-986278 Dose 2<br> | Drug: BMS-986278<br>* Specified dose on specified days<br>|
| Placebo Comparator: BMS-986278 Placebo<br> | Drug: BMS-986278 Placebo<br>* Specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change from baseline in forced vital capacity (FVC) measured in mL |  | At Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease progression | Disease progression will be measured by the time to first disease progression event in at least 1 of the following parameters: Absolute percent predicted forced vital capacity (ppFVC) decline of ≥ 10% from baseline Acute exacerbation of pulmonary fibrosis Lung fibrosis-related hospitalization All-cause mortality | Up to approximately 4 years | 
| Change from baseline in Living with Pulmonary Fibrosis Questionnaire (L-PF) cough domain score |  | At Week 52 and up to approximately 4 years | 
| Change from baseline in L-PF dyspnea domain score |  | At Week 52 and up to approximately 4 years | 
| Change from baseline in walking distance measured in 6-minute walk test (6MWT) |  | At Week 52 | 
| Time to the first occurrence of any of the components of the composite endpoint: time to first acute exacerbation of pulmonary fibrosis, first Lung fibrosis-related hospitalization, or all-cause mortality |  | Up to approximately 4 years | 
| Time to absolute percent ppFVC decline of ≥ 10% from baseline |  | Up to approximately 4 years | 
| Time to first acute exacerbation of pulmonary fibrosis |  | Up to approximately 4 years | 
| Time to first lung fibrosis-related hospitalization |  | Up to approximately 4 years | 
| Time to all-cause mortality |  | Up to approximately 4 years | 
| Change from baseline in L-PF fatigue domain score |  | At Week 52 and up to approximately 4 years | 
| Change from baseline in L-PF impact module score |  | At Week 52 and up to approximately 4 years | 
| Change from baseline in cough numeric rating scale (NRS) |  | At Week 52 and up to approximately 4 years | 
| Change from baseline in EuroQol 5 Dimension 5 Level (EQ-5D-5L) health utility index score |  | At Week 52 | 
| Change from baseline in EQ-5D-5L visual analog scale score |  | At Week 52 | 
| Rate of decline from baseline in FVC (mL) |  | At Week 52 | 
| Rate of decline in ppFVC from baseline |  | At Week 52 | 
| Change in ppFVC from baseline |  | At Week 52 | 
| Proportion of participants with absolute decline in ppFVC ≥10% |  | At Week 52 | 
| Proportion of participants with relative decline in ppFVC ≥10% |  | At Week 52 | 
| Change from baseline in single-breath diffusing capacity of the lung for carbon monoxide (DLCO SB) (corrected for hemoglobin) (mL/min/mm Hg) |  | At Week 52 | 
| Change in percent predicted single breath diffusing capacity of the lung for carbon monoxide (ppDLCO SB) (corrected for hemoglobin) from baseline |  | At Week 52 | 
| Change from baseline in quantitative lung fibrosis (QLF) score via high-resolution computed tomography (HRCT) |  | At Week 52 | 
| Number of participants with Adverse Events (AEs) |  | Up to 28 days after last dose | 
| Number of participants with Serious AEs (SAEs) |  | Up to 28 days after last dose | 
| Number of participants with AEs leading to early discontinuation of investigational medicinal product (IMP) |  | Up to 28 days after last dose | 
| Number of treatment-emergent deaths |  | Up to 28 days after last dose | 
| Number of participants with clinical laboratory abnormalities |  | Up to 28 days after last dose | 
| Number of participants with electrocardiogram (ECG) abnormalities |  | Up to 28 days after last dose | 
| Number of participants with vital sign abnormalities |  | Up to 28 days after last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LPA1 antagonist, BMS-986278, Pulmonary fibrosis, Interstitial lung disease, Rheumatoid Arthritis, Connective Tissue Disorders, Sarcoidosis, Scleroderma, Fibrosis, Antifibrotic therapy