A Phase 2 Trial of ENV-101 in Patients With Lung Fibrosis (WHISTLE-PF Trial)

Prior treatment

• Active or suspected alcohol or drug abuse in the opinion of the Investigator.
• Currently enrolled in another investigational device or drug trial, or less than 3 months from study start since ending another investigational device or drug trial(s) or receiving other investigational treatment(s).
• Major surgery requiring hospitalization (according to the Investigator) performed within 3 months prior to study start or planned during the course of the trial. Being on a transplant list is allowed.
• Occurrence of serious illness requiring hospitalization within 90 days prior to study start.
• Current or previous use (within 28 days prior to study start) of the following:
  • Endothelin receptor antagonist
  • Riociguat
  • Prostacyclin or prostacyclin analogue
  • Radiation to the lungs
  • Oral corticosteroids \>15 mg/day
• Use of cyclophosphamide or tocilizumab within 8 weeks, or rituximab within 6 months, prior to study start.
• Use of drugs that are known moderate or stronger CYP3A4 inhibitors or inducers within 14 days prior to study start. Patients must also agree not to eat fruits that inhibit CYP3A4 such as grapefruit, Seville oranges, pomelo and star fruit.
• Patients of reproductive potential who are sexually active and unwilling to use birth control for the duration of the study and for 3 months after their final dose of study drug.
• Patients that are unwilling to refrain from blood or blood product donation for the duration of the study and for 30 days after their final dose of study drug.
• Males who are unwilling to refrain from sperm donation and females who are unwilling to refrain from egg donation for the duration of the study and for 3 months after their final dose of study drug.
• Patients who have previously taken ENV-101.

Other illness

• Evidence of other known causes of interstitial lung disease (ILD).
• History of malignancy, including carcinoma during the preceding 5 years from study start, with the following exceptions:
  • Prior history of in situ melanoma, basal or squamous cell skin cancer if treated with curative therapy.
  • Patients with prostate cancer that are managed by surveillance.
  • Patients with ductal carcinoma in situ, treated surgically with curative intent.
• Patients with moderate to severe hepatic impairment (Child-Pugh B and C).
• Presence of active infection at study start or confirmed active human immunodeficiency virus (HIV), Hepatitis B virus (HBV) or Hepatitis C virus (HCV).
• Patients with a history of a severe allergic reaction or anaphylactic reaction or known hypersensitivity to any component of ENV-101.

Other

• Forced expiratory volume in one second (FEV1)/FVC ratio \<0.7 at study start.
• Smoking (including vaping) within 6 months of study start; current smoker, or unwillingness to refrain from smoking during the clinical trial duration.
• Females that are pregnant or nursing.

• Patients ≥ 40 years old with an IPF diagnosis as confirmed by the Investigator.
• Percent predicted FVC of ≥ 45% at study start.
• Percent predicted diffusing capacity of lung for carbon monoxide (DLCO) ≥ 25%, adjusted for hemoglobin (Hgb) at study start.
• Ability to perform spirometry tests.
• Either stable treatment with standard of care (SoC) \[i.e., antifibrotics, immunosuppressants (PPF only)\] for at least 3 months prior to study start or not treated with SoC for at least 8 weeks prior to study start.