NCT05976217

Safety and Efficacy of Venetoclax in Idiopathic Pulmonary Fibrosis

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: University of Alabama at Birmingham · Academic / Other
• Sex: All
• Age: 40 Years – 85 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Idiopathic Pulmonary Fibrosis

Interventions

Type	Name	Description
DRUG	Venetoclax	100 mg daily by mouth for 3 weeks This drug inhibits a protein (Bcl-2) that protects cells from undergoing programmed cell death.

Timeline

• Start date: 2023-10-01
• Primary completion: 2024-03-18
• Completion: 2024-03-20
• First posted: 2023-08-04
• Last updated: 2024-03-28

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study