Safety and Efficacy of a Lysophosphatidic Acid Receptor Antagonist in Idiopathic Pulmonary Fibrosis
Condition: Idiopathic Pulmonary Fibrosis
MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis
Intervention: BMS-986020; Placebo matching with BMS-986020
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 325.0
Sex: All
Minimum age: 40 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: IPF

Summary:

      The purpose of this study is to determine if study drug (BMS-986020) dose of 600 mg once
      daily or 600 mg twice daily for 26 weeks compared with placebo will reduce the decline in
      forced vital capacity (FVC) and will be well tolerated in subjects with idiopathic pulmonary
      fibrosis (IPF).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Are between the ages of 40 and 90 years, inclusive, at randomization.

          -  Have clinical symptoms consistent with IPF.

          -  Have first received a diagnosis of IPF less than 6 years before randomization. The
             date of diagnosis is defined as the date of the first available imaging or surgical
             lung biopsy consistent with IPF/UIP.

          -  Have a diagnosis of usual interstitial pulmonary fibrosis (UIP) or IPF by HRCT or
             surgical lung biopsy (SLB).

          -  Extent of fibrotic changes (honeycombing, reticular changes) greater than the extent
             of emphysema on HRCT scan.

          -  Have no features supporting an alternative diagnosis on transbronchial biopsy, BAL, or
             SLB, if performed.

          -  Have percent predicted post-bronchodilator FVC between 45% and 90%, inclusive, at
             screening.

          -  Have a change in post-bronchodilator FVC (measured in liters) between screening and
             day 1 that is less than a 10% relative difference, calculated as: the absolute value
             of 100% * (screening FVC (L) - day 1 FVC (L)) / screening FVC (L).

          -  Have carbon monoxide diffusing capacity (DLCO) between 30% and 80% (adjusted for
             hemoglobin and altitude), inclusive, at screening.

          -  Have no evidence of improvement in measures of IPF disease severity over the preceding
             year, in the investigator's opinion.

          -  Be able to walk 150 meters or more at screening.

          -  Demonstrate an exertional decrease in oxygen saturation of 2 percentage points or
             greater at screening (may be performed with supplemental oxygen titrating to keep
             oxygen saturation levels >88%).

          -  Are able to understand and sign a written informed consent form.

          -  Are able to understand the importance of adherence to study treatment and the study
             protocol and are willing to comply with all study requirements, including the
             concomitant medication restrictions, throughout the study.

          -  Women of childbearing potential (WOCBP) and men who are sexually active with WOCBP
             must use acceptable method(s) of contraception. The individual methods of
             contraception and duration should be determined in consultation with the investigator.
             WOCBP must follow instructions for birth control when the half-life of the
             investigational drug is less than 24 hours, contraception should be continued for a
             period of 30 days after the last dose of investigational product.

               1. Women must have a negative urine pregnancy test within 24 hours prior to the
                  start of investigational product.

               2. Women must not be breastfeeding.

               3. Men who are sexually active with WOCBP must use any contraceptive method with a
                  failure rate of less than 1% per year. Men that are sexually active with WOCBP
                  must follow instructions for birth control when the half-life of the
                  investigational drug is less than 24 hours, contraception should be continued for
                  a period of 90 days after the last dose of investigational product.

               4. Women who are not of childbearing potential (i.e., who are postmenopausal or
                  surgically sterile) and azoospermic men do not require contraception.

        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.

        Other Exclusion Criteria

          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.