Safety and Efficacy of Venetoclax in Idiopathic Pulmonary Fibrosis

Inclusion Criteria:

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

Exclusion Criteria:

1. Diagnosis of major comorbidities expected to interfere with study participation.
2. History of malignancy within the last 5 years, excluding basal or squamous cell skincancer.
3. The occurrence of any acute infection requiring systemic antibiotic therapy within 2weeks prior to Screening (Visit 1).
4. Treatment for >14 days within the preceding month with >20 mg. prednisone (orequivalent) 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.
5. Concurrent participation in other experimental trials.
6. Fertile women who do not agree to abstinence or an effective form of contraception (asapproved by the investigator), or who are breast feeding, for 4 weeks beforerandomization until 90 days after the last administration of study medication (orplacebo).
7. Men who are not surgically sterile and do not agree to remain abstinent fromheterosexual intercourse or use effective contraception (as approved by theinvestigator), and refrain from donating sperm, from the time of giving informedconsent until 90 days after the last administration of study medication (or placebo).
8. Subjects with known hypersensitivity to capsule "bulking" agents.
9. A history of bone marrow disorder including aplastic anemia, or marked anemia definedas hemoglobin < 10.0 g/dL (or 6.2 mmol/L).
10. Severe cardiovascular disease, defined as any of the following within the preceding 12weeks: acute myocardial infarction or unstable angina, a coronary revascularizationprocedure, congestive heart failure (NYHA Class III or IV), or stroke, including atransient ischemic attack.
11. Evidence of cardiac conducting abnormalities, defined as second- or third-degree AVblock not successfully treated with a pacemaker, or a personal or family history oflong QT syndrome (QTc interval >450 msec for males or 470 msec for females).
12. End-stage renal disease requiring dialysis.
13. Undergoing transplantation evaluation or listed with the United Network for OrganSharing (UNOS) as a lung transplantation candidate at the time of enrollment in thistrial.
14. Liver function tests (transaminases, alkaline phosphatase, direct and total bilirubin) >2x upper limit of normal values.
15. Systemically administered potent CYP3A4 inhibitors or inducers are prohibited duringthe 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.