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

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).

• Drug: BMS-986020
• Drug: Placebo matching with BMS-986020

• Experimental: Arm 1: BMS 986020, 600 mg. once daily
  BMS-986020, 600 mg tablets, by mouth, once daily, 26 weeks
  Intervention: Drug: BMS-986020
• Experimental: Arm 2: BMS-986020, 600 mg twice daily
  BMS-986020, 600 mg tablets, by mouth, twice daily, 26 weeks
  Intervention: Drug: BMS-986020
• Placebo Comparator: Arm 3: Placebo matching with BMS-986020
  Placebo, 0 mg tablets, by mouth, twice daily, 26 weeks
  Intervention: Drug: Placebo matching with BMS-986020

Inclusion Criteria:

• Are between the ages of 40 and 80 years, inclusive, at randomization.
• Have clinical symptoms consistent with IPF.
• Have first received a diagnosis of IPF at least 6 months and no more than 48 months before randomization. The date of diagnosis is defined as the date of the first available HRCT or surgical lung biopsy consistent with IPF/UIP.
• Have a diagnosis of usual interstitial pulmonary fibrosis (UIP) or IPF by high resolution computed tomography (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 50% and 80%, 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 during the 6 minute walk test (6MWT) at screening.
• Demonstrate a decrease in oxygen saturation of 2 percentage points or greater during the 6MWT 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.

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.
  2. Has a known explanation for interstitial lung disease.
  3. Has a clinical diagnosis of any connective tissue disease.
  4. Currently has clinically significant asthma or chronic obstructive pulmonary disease.
  5. Has clinical evidence of active infection.
  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.
  11. Has a history of alcohol or substance abuse in the past 2 years.
  12. Has a family or personal history of long QT syndrome and/or Torsades de Pointes (polymorphic ventricular tachycardia).

  13. Has used any of the following specific therapies within 7 days before screening:

      1. Investigational therapy, defined as any drug that has not been approved for marketing for any indication in the country of the participating site.
      2. Any cytotoxic, immunosuppressive, cytokine-modulating, or receptor-antagonist agent, including, but not limited to, azathioprine, bosetan, ambrisentan, cyclophosphamide, cyclosporine, etanercept, iloprost, infliximab, leukotriene antagonists, methotrexate, mycophenolate mofetil, tacrolimus, montelukast, tetrathiomolybdate, tumor necrosis factor alpha inhibitors, NAC, imatinib mesylate, interferon gamma-1b, pirfenidone, and tyrosine kinase inhibitors.
      3. Colchicine, heparin, and warfarin. Sildenafil (daily use) may be used if given for a non-IPF indication if there is no clinically acceptable alternate therapy for the same indication; intermittent use for erectile dysfunction is allowed.
      4. Intermittent use of corticosteroids is allowed for acute respiratory worsening.
      5. Ketoconazole, cyclosporine and steroids for topical and ophthalmic use is permitted.