Safety and Efficacy of Venetoclax in Idiopathic Pulmonary Fibrosis
Status:
Completed
Trial end date:
2024-03-20
Target enrollment:
Participant gender:
Summary
Based on preclinical data, investigators hypothesize that apoptosis resistance in
monocyte-derived macrophages (MDMs) have a decisive role in the development of idiopathic
pulmonary fibrosis (IPF). Specifically, macrophages from subjects with IPF have increased
expression of Bcl-2 in mitochondria. In preclinical models of IPF, a conditional deletion of
Bcl-2 in MDMs reverses established fibrosis by inducing apoptosis. Additional evidence to
suggest that Bcl-2 expression in MDM mitochondria is a therapeutic target for IPF as
administration of the Bcl-2 inhibitor, ABT-199 (Venetoclax), showed marked efficacy in
preclinical models of IPF by inducing apoptosis of MDMs and reversing established fibrosis.
ABT-199 is an orally available mimetic of the BH3 domain of Bcl-2, which is the domain the
anchors Bcl-2 in the mitochondria to inhibit apoptosis. ABT-199 has shown therapeutic
efficacy and good safety and tolerability in patients with chronic lymphocytic leukemia.
Investigators anticipate that treatment with ABT-199 could result in significant benefit for
IPF patients that have a life expectancy of 3-5 years. As there is no curative therapy for
IPF, this clinical trial has the potential to substantially alter treatment approaches in
patients with IPF.