Safety and Efficacy of a Lysophosphatidic Acid Receptor Antagonist in Idiopathic Pulmonary Fibrosis

Exclusion Criteria

• •Target Disease Exclusions
• •1. Has significant clinical worsening of IPF between screening and day 1 (during the screening process), in the opinion of the investigator.
• •2. Has forced expiratory volume in 1 second (FEV1)/FVC ratio less than 0.8 after administration of bronchodilator at screening.
• •3. Has bronchodilator response, defined by an absolute increase of 12% or greater and an increase of 200 mL in FEV1 or FVC or both after bronchodilator use compared with the values before bronchodilator use at screening.
• •Medical History and Concurrent Diseases
• •1. Has a history of clinically significant environmental exposure known to cause pulmonary fibrosis, including, but not limited to, drugs (such as amiodarone), asbestos, beryllium, radiation, and domestic birds.
• •2. Has a known explanation for interstitial lung disease, including, but not limited to, radiation, drug toxicity, sarcoidosis, hypersensitivity, pneumonitis, bronchiolitis, obliterans, organizing pneumonia, human immunodeficiency virus (HIV), viral hepatitis, and cancer.
• •3. Has a clinical diagnosis of any connective tissue disease, including, but not limited to, scleroderma, polymyositis/dermatomyositis, systemic lupus erythematosus, rheumatoid arthritis, and undifferentiated connective tissue disease.
• •4. Currently has clinically significant asthma or chronic obstructive pulmonary disease.
• •5. Has clinical evidence of active infection, including, but not limited to, bronchitis, pneumonia, sinusitis, urinary tract infection, and cellulitis.
• •6. Has any history of malignancy likely to result in significant disability or likely to require significant medical or surgical intervention within the next 2 years. This does not include minor surgical procedures for localized cancer (e.g., basal cell carcinoma).
• •7. Has any condition other than IPF that, in the opinion of the investigator, is likely to result in the death of the subject within the next 2 years.
• •8. Has a history of end-stage liver disease.
• •9. Has a history of end-stage renal disease requiring dialysis.
• •10. Has a history of unstable or deteriorating cardiac or pulmonary disease (other than IPF) within the previous 6 months, including, but not limited to, the following: i. Unstable angina pectoris or myocardial infarction ii. Congestive heart failure requiring hospitalization iii. Uncontrolled clinically significant arrhythmias
• •11. Has any condition that, in the opinion of the investigator, might be significantly exacerbated by the known side effects associated with the administration of BMS-986020.
• •12. Has a history of alcohol or substance abuse in the past 2 years.
• •13. Has a family or personal history of long QT syndrome and/or Torsades de Pointes (polymorphic ventricular tachycardia).
• •14. Has used any of the excluded medications per Appendix 1 of the Protocol, which includes, but is not limited to:
• •* current treatment with pirfenidone or nintedanib
• •* use of over-the-counter medications and herbal preparations, within 4 weeks before study drug administration except those medications cleared by the BMS medical monitor
• •* For subjects taking statins, there are restrictions on the maximum allowable doses for statins listed below. If subjects are currently taking statins and their doses are higher than those mentioned below, please reduce the dose to the maximum allowable dose.
• •Additionally, if subjects are on statins and ready to start dosing, these subjects should limit statin doses by maximal allowable dose or lower for at least 5 days prior to the first BMS-986020 dosing. Shorter durations may be considered in select cases after discussion with the medical monitor.
• •Maximum allowable dose for statins:
• •Simvastatin 20 mg QD
• •Pitavastatin 2 mg QD
• •Atorvastatin 40 mg QD
• •Pravastatin 40 mg QD
• •Rosuvastatin 20 mg QD
• •Lovastatin 40 mg QD
• •Fluvastatin 40 mg QD
• •Prednisone is allowed up to a maximum of 15 mg po daily
• •Pirfenidone or nintedanib dosing for a maximum of 3 months in the prior 12 months is permitted with a 4 week washout period prior to dosing with BMS-986020.
• •Physical and Laboratory Test Findings
• •1. Has any of the following liver-function test criteria above the specified limits: total bilirubin \>1.5 x ULN, excluding subjects with Gilbert's syndrome; aspartate or alanine aminotransferase (AST/SGOT or ALT/SGPT) greater than 3 x ULN; alkaline phosphatase greater than 2.5 x ULN.
• •2. Has creatinine clearance less than 30 mL/minute, calculated using the Cockcroft-Gault formula.
• •3. Has ECG result with a QT interval by Fridericia's correction (QTcF) of 500 msec or greater or an uncorrected QT of 500 msec or greater at screening. Note: For subjects with a machine read QT interval of \>500 msec, if their heart rate is \> 100 bpm, the machine read QT interval (either corrected or not) may not be accurate. If the investigator is uncertain about the QT abnormality, it is recommended that ECGs be over-read by a cardiologist. The manually read QT interval by a cardiologist should be used for assessment of eligibility whenever possible.
• •Allergies and Adverse Drug Reaction Has had prior use of BMS-986020 or has known hypersensitivity to any of the components of study treatment.
• •1. Is not a suitable candidate for enrollment or is unlikely to comply with the requirements of this study, in the opinion of the investigator.
• •2. Has smoked cigarettes within 4 weeks or screening or is unwilling to avoid tobacco products throughout the study.
• •3. Is expected to receive a lung transplant within 1 year from randomization or, for subjects at sites in the United States, is on a lung-transplant waiting list at screening.
• •4. Prisoners or subjects who are involuntarily incarcerated.
• •5. Subjects who are compulsorily detained for treatment either of a psychiatric or physical (e.g., infectious disease) illness.
• •6. Inability to comply with restrictions and prohibited activities/treatments as listed in Section 3.3 of the Protocol.