Progressive Pulmonary Fibrosis
Conditions
Keywords
BMS-986278, LPA1 antagonist, Pulmonary fibrosis, Interstitial lung disease, Rheumatoid Arthritis, Connective Tissue Disorders, Sarcoidosis, Scleroderma, Fibrosis, Antifibrotic therapy
Brief summary
The purpose of this study is to evaluate the efficacy, safety, and tolerability of BMS-986278 in Participants with Progressive Pulmonary Fibrosis.
Interventions
DRUGBMS-986278
Specified dose on specified days
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of interstitial lung disease (ILD) with features consistent with progressive ILD within 24 months prior to screening, and ≥ 10% extent of fibrosis 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) are permitted provided that the participant is on a stable dose for at least 90 days prior to screening. If not currently on traditional DMARD, participants must not have taken these medications within 28 days prior to screening. * 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. If not currently on Biologic DMARD or JAK inhibitor, participants must not have taken these medications within 28 days prior to screening. * 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. * Participants who exhibit symptoms of heart failure at rest. * Participants who have a current malignancy; a previous malignancy with less than 2 years free of recurrence; and a biopsy that is suspicious for malignancy and the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory, or other diagnostic evaluations. * Use of systemic corticosteroids equivalent to prednisone \> 15 mg/day is not allowed within 4 weeks prior to screening and during the study. * Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants that experience spontaneous syncopal events | At approximately 4 weeks | Cohort 1 |
| Absolute change from baseline in forced vital capacity (FVC) measured in mL | At Week 52 | Cohort 2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants who discontinued treatment due to any low BP-related Adverse Events | Up to approximately 3 years | Cohort 1 |
| Disease progression | Up to approximately 3 years | Cohort 2 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 * Respiratory-related hospitalization * All-cause mortality |
| Change from baseline in Living with Pulmonary Fibrosis Questionnaire (L-PF) cough domain score | At Week 52 and up to approximately 3 years | Cohort 2 |
| Change from baseline in L-PF dyspnea domain score | At Week 52 and up to approximately 3 years | Cohort 2 |
| Change from baseline in walking distance measured in 6-minute walk test (6MWT) | At Week 52 | Cohort 2 |
| Time to the first occurrence of any of the components of the composite endpoint: time to first acute exacerbation of pulmonary fibrosis, first respiratory-related hospitalization, or all-cause mortality | Up to approximately 3 years | Cohort 2 |
| Time to absolute percent ppFVC decline of ≥ 10% from baseline | Up to approximately 3 years | Cohort 2 |
| Time to first acute exacerbation of pulmonary fibrosis | Up to approximately 3 years | Cohort 2 |
| Time to first respiratory-related hospitalization | Up to approximately 3 years | Cohort 2 |
| Time to first pulmonary fibrosis-related hospitalization. | Up to approximately 3 years | Cohort 2 |
| Time to all-cause mortality | Up to approximately 3 years | Cohort 2 |
| Change from baseline in L-PF fatigue domain score | At Week 52 and up to approximately 3 years | Cohort 2 |
| Change from baseline in L-PF impacts module score | At Week 52 and up to approximately 3 years | Cohort 2 |
| Change from baseline in cough numeric rating scale (NRS) | At Week 52 and up to approximately 3 years | Cohort 2 |
| Change from baseline in EuroQol 5 Dimension 5 Level (EQ-5D-5L) health utility index score | At Week 52 | Cohort 2 |
| Change from baseline in EQ-5D-5L visual analog scale score | At Week 52 | Cohort 2 |
| Rate of decline from baseline in FVC (mL) | At Week 52 | Cohort 2 |
| Rate of decline in ppFVC from baseline | At Week 52 | Cohort 2 |
| Change in ppFVC from baseline | At Week 52 | Cohort 2 |
| Proportion of participants with absolute decline in ppFVC ≥10% | At Week 52 | Cohort 2 |
| Proportion of participants with relative decline in ppFVC ≥10% | At Week 52 | Cohort 2 |
| 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 | Cohort 2 |
| Change in percent predicted single breath diffusing capacity of the lung for carbon monoxide (ppDLCO SB) (corrected for hemoglobin) from baseline | At Week 52 | Cohort 2 |
| Change from baseline in quantitative lung fibrosis (QLF) score via high-resolution computed tomography (HRCT) | At Week 52 | Cohort 2 |
| Number of participants with Adverse Events (AEs) | Up to 28 days after last dose | Cohort 2 |
| Number of participants with Serious AEs (SAEs) | Up to 28 days after last dose | Cohort 2 |
| Number of participants with AEs leading to early discontinuation of investigational medicinal product (IMP) | Up to 28 days after last dose | Cohort 2 |
| Number of participants with AEs related to IMP | Up to 28 days after last dose | Cohort 2 |
| Number of treatment-emergent deaths | Up to 28 days after last dose | Cohort 2 |
| Number of participants with clinical laboratory abnormalities | Up to 28 days after last dose | Cohort 2 |
| Number of participants with electrocardiogram (ECG) abnormalities | Up to 28 days after last dose | Cohort 2 |
| Number of participants with vital sign abnormalities | Up to 28 days after last dose | Cohort 2 |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, India, Ireland, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, Peru, Poland, Portugal, Puerto Rico, South Korea, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Outcome results
None listed