“Senolytics Dasatinib and Quercetin in Idiopathic Pulmonary Fibrosis: Results of a Phase I, Single-Blind, Single-Center, Randomized, Placebo-Controlled Pilot Trial on Feasibility and Tolerability”, 2023 (; backlinks):
Background: Idiopathic pulmonary fibrosis (IPF) is an age-related, chronic, irreversible fibrotic lung disease. IPF is associated with increased senescent cells burden, which may be alleviated with administration of senescent cell targeting drugs termed ‘senolytics’. We previously conducted an open-label single-arm pilot study of the senolytic combination of dasatinib and quercetin (D + Q) in patients with IPF but lack of control group limited interpretation and next-stage trial planning. The primary objective of this confirmatory randomized placebo-controlled pilot trial (RCT;NCT02874989) was to report adverse events with D + Q and inform study feasibility for future efficacy trials.
Method: 12 participants with IPF aged >50 years were blinded and randomized at a 1:1 ratio to either receive 3 weeks of D + Q (D: 100 mg/d and Q: 1250 mg/d, 3 consecutive days per week) or matching placebo.
Findings: All participants completed the scheduled drug dosing regimen (108/108 doses) and planned assessments (60/60). While the placebo arm reported fewer overall non-serious AEs (65 vs 22), there were no serious adverse events related to D + Q. Most AEs in the D + Q arm are common in IPF patients or anticipated side effects of D. Sleep disturbances and anxiety were disproportionately represented in the D + Q arm (4/6 vs 0/6). Frailty, pulmonary, or physical function were explored before and after intermittent D + Q; though under-powered to evaluate change, these measures do not appear to differ meaningfully between groups.
Interpretation: Intermittently-dosed D + Q in patients with IPF is feasible and generally well-tolerated. Further prospective studies, such as a larger RCT, are needed to confirm the safety and efficacy of D + Q in patients with IPF.