Abstract Rationale Idiopathic pulmonary fibrosis (IPF) is a progressive, lethal lung disease characterized by accumulating fibrosis and impaired respiratory function and with no approved treatments that reverse or stop progression. Oral administration of rentosertib (INS018₀55), a TNIK inhibitor, has been demonstrated to be generally safe, well-tolerated, and preliminarily effective in restoring lung function in IPF patients across preclinical, Phase 1, and Phase 2a (GENESIS-IPF) clinical studies. Furthermore, a 28-day toxicology study of inhaled rentosertib in healthy animals showed a favorable safety profile with no drug-related adverse effects observed. These results support investigation as an inhalable treatment for IPF. Methods This study is a randomized, double-blind, placebo-controlled, single- and multiple-dosed Phase 1 trial conducted in healthy subjects aged 18-54 years at a single site in China. The primary objectives are to determine the safety, tolerability, and pharmacokinetics (PK) profiles of single (Part A) and multiple (Part B) ascending doses of inhaled rentosertib. In Part A, participants (n = 40) will be assigned to one of five dose groups and receive placebo or a single administration of rentosertib or placebo via jet nebulizer with 0. 5, 5, 20, 40, or 80 mg of rentosertib based on group assignment. In Part B, participants (n = 24) will be randomly assigned to one of three groups, receiving placebo or inhaled rentosertib at 5 mg once-daily, 10 mg twice-daily, or 20 mg twice-daily for 14 days. An additional cohort comprised of older participants aged 55-75 years receiving 10 mg rentosertib once-daily or placebo may be added based on initial safety data. Safety endpoints, including incidence and severity of adverse events, changes in clinical laboratory parameters such as hematology, chemistry, and urinalysis values, changes in 12-lead ECG, vital signs, pulse oximetry, and spirometry will be assessed through day 28 follow-up. PK endpoints will be assessed through serial blood sampling during the treatment period and periodically thereafter. Conclusions The study will evaluate the safety, tolerability, and PK of inhaled rentosertib (INS018₀55) in healthy adults. These results are expected to enhance understanding of the inhaled administration route of rentosertib and guide future clinical trial design in patients with IPF. This abstract is funded by: Insilico Medicine
Satler et al. (Fri,) studied this question.