Safety and Efficacy of Venetoclax in Idiopathic Pulmonary Fibrosis

Prior treatment

• The occurrence of any acute infection requiring systemic antibiotic therapy within 2 weeks prior to Screening (Visit 1).
• Concurrent participation in other experimental trials.
• Fertile women who do not agree to abstinence or an effective form of contraception (as approved by the investigator), or who are breast feeding, for 4 weeks before randomization until 90 days after the last administration of study medication (or placebo).
• Men who are not surgically sterile and do not agree to remain abstinent from heterosexual intercourse or use effective contraception (as approved by the investigator), and refrain from donating sperm, from the time of giving informed consent until 90 days after the last administration of study medication (or placebo).
• Undergoing transplantation evaluation or listed with the United Network for Organ Sharing (UNOS) as a lung transplantation candidate at the time of enrollment in this trial.
• Systemically administered potent CYP3A4 inhibitors or inducers are prohibited during the 24-week treatment period.
  • Inhibitors include: pirfenidone, boceprevir, cobicistat, conivaptan, ritonavir, itraconazole, ketoconazole, telaprevir, troleandomycin, voriconazole, clarithromycin, diltiazem, idelalisib, nefazodone, nelfinavir.
  • Inducers include: carbamazepine, enzalutamide, mitotane, phenytoin, rifampin.

Other illness

• History of malignancy within the last 5 years, excluding basal or squamous cell skin cancer.
• Treatment for \>14 days within the preceding month with \>20 mg. prednisone (or equivalent) or any treatment during the last month with a cellular immunosuppressant (e.g., cyclophosphamide, methotrexate, calcineurin inhibitors, azathioprine, etc.), given increased risks of opportunistic infections.
• Subjects with known hypersensitivity to capsule "bulking" agents.
• Severe cardiovascular disease, defined as any of the following within the preceding 12 weeks: acute myocardial infarction or unstable angina, a coronary revascularization procedure, congestive heart failure (NYHA Class III or IV), or stroke, including a transient ischemic attack.
• End-stage renal disease requiring dialysis.

Lab values

• A history of bone marrow disorder including aplastic anemia, or marked anemia defined as hemoglobin \< 10.0 g/dL (or 6.2 mmol/L).
• Evidence of cardiac conducting abnormalities, defined as second- or third-degree AV block not successfully treated with a pacemaker, or a personal or family history of long QT syndrome (QTc interval \>450 msec for males or 470 msec for females).
• Liver function tests (transaminases, alkaline phosphatase, direct and total bilirubin) \>2x upper limit of normal values.

Other

• Diagnosis of major comorbidities expected to interfere with study participation.

• Age between 40-85 years old, male and female.
• A diagnosis of IPF that fulfills current ATS/ERS Consensus Criteria (1).
• IPF duration \<5 years, based on the date of definitive diagnosis.
• Ability and willingness to give informed consent and adhere to study requirements.
• Forced Vital Capacity (FVC) \> 50% predicted values.