Bardoxolone Methyl Evaluation in Patients With Pulmonary Hypertension (PH) - LARIAT
Condition: Pulmonary Arterial Hypertension; Pulmonary Hypertension; Interstitial Lung Disease; Idiopathic Interstitial Pneumonia; Idiopathic Pulmonary Fibrosis; Sarcoidosis; Respiratory Bronchiolitis Associated Interstitial Lung Disease; Desquamative Interstitial Pneumonia; Cryptogenic Organizing Pneumonia; Acute Interstitial Pneumonitis; Idiopathic Lymphoid Interstitial Pneumonia; Idiopathic Pleuroparenchymal Fibroelastosis
MeSH terms: Pneumonia; Bronchiolitis; Lung Diseases; Hypertension, Pulmonary; Pulmonary Fibrosis; Pulmonary Arterial Hypertension; Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial; Idiopathic Interstitial Pneumonias; Hamman-Rich Syndrome; Organizing Pneumonia; Cryptogenic Organizing Pneumonia; Hypertension; Sarcoidosis; Fibrosis
Study type: Interventional
Phase: Phase 2

Summary: 
      This study assesses the safety and efficacy of bardoxolone methyl relative to placebo in
      patients with pulmonary hypertension to determine the recommended dose range, evaluate the
      change from baseline in 6-minute walk distance (6MWD) and determine the effect of Bardoxolone
      methyl in pulmonary hypertension associated with connective tissue disease, interstitial lung
      disease, and idiopathic etiologies, including subsets of patients with WHO Group III or WHO
      Group V PH following 16 weeks of study participation.
    

Detailed description: 
      The molecular and pharmacological effects of bardoxolone methyl are broad through its
      induction of Nrf2 and suppression of NF-κB. Bardoxolone methyl may therefore address multiple
      facets of the pathophysiology of PH because it suppresses activation of proinflammatory
      mediators, enhances endothelial NO bioavailability, improves metabolic dysfunction,
      suppresses vascular proliferation, and prevents maladaptive remodeling. Furthermore, while
      existing therapies primarily target only smooth muscle cells, bardoxolone methyl targets
      multiple cell types relevant to PH, including endothelial cells, smooth muscle cells, and
      macrophages.

      This is a two-part study.

      Part 1: Part 1 of the study will include a dose-ranging phase and a dose-titration phase.

      Part 2 (extension period): All patients from Part 1 who complete the 16-week treatment period
      as planned will be eligible to continue directly into the extension period to evaluate the
      intermediate and long-term safety and efficacy of bardoxolone methyl.

      Study Sponsor, originally Reata Pharmaceuticals, Inc., is now Reata Pharmaceuticals, Inc., a
      wholly owned subsidiary of Biogen.
    

Intervention name(s): Bardoxolone methyl; Placebo
Intervention type(s): Drug; Drug
Other intervention name(s): RTA 402 capsules
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Pulmonary Arterial Hypertension; PAH; Bardoxolone methyl; 6-minute walk distance; CDDO-me; RTA 402; Pulmonary Hypertension; Interstitial Lung Disease; Idiopathic Interstitial Pneumonia; Idiopathic Pulmonary Fibrosis; Sarcoidosis; Respiratory Bronchiolitis Associated ILD; Desquamative Interstitial Pneumonia; Cryptogenic Organizing Pneumonia; Acute Interstitial Pneumonitis; Idiopathic Lymphoid Interstitial Pneumonia; Idiopathic Pleuroparenchymal Fibroelastosis