A Phase I Evaluation of the Safety and Tolerability of Pirfenidone in Idiopathic Subglottic Stenosis

Summary

Idiopathic subglottic stenosis (iSGS) is a rare condition where scar tissue forms just below the vocal cords and in the upper windpipe, making the airway narrow. People with iSGS often feel short of breath, hear noisy breathing, and notice changes in their voice. Many need repeated operations and steroid injections to open the airway, but the narrowing usually comes back, so these treatments are not a cure. Recent research from a Canadian iSGS registry and biobank has shown that this disease is driven by overactive scarring pathways, similar to those seen in idiopathic pulmonary fibrosis (IPF), a serious lung disease. Pirfenidone is an oral medication already approved for IPF that works by slowing down the cells and signals that cause scarring. Because the same scarring pathways appear to be active in iSGS, pirfenidone may be able to slow or reduce the build-up of scar tissue in the airway. In this study, adults with iSGS will be randomly assigned (like flipping a coin) to receive either pirfenidone or a placebo (a look-alike pill with no active drug) for 52 weeks, in addition to their usual intralesional steroid injections. The pirfenidone dose will be increased gradually over the first two weeks up to a regular dose taken three times a day with food, which is the same schedule used in patients with IPF. Participants and their doctors will not know which treatment they are getting until the end of the study, unless this needs to be revealed for safety reasons. The main goal of this trial is to see how safe pirfenidone is for people with iSGS and how well they can tolerate taking it for one year. The study team will watch closely for side effects such as stomach upset, skin rash or sensitivity to sunlight, tiredness, and changes in liver blood tests. They will also look for early signs that pirfenidone may help, such as longer time until the next airway dilation, better breathing tests, and improvements in breathlessness and voice-related quality of life scores. Participants will be followed for a total of up to two years, including one year on study medication and one year of follow-up. This study may not directly help every person who takes part, but the results will provide important information about whether pirfenidone is safe in iSGS and whether it could become the first medication to slow down this scarring airway disease.

Timeline

Start

2026-12-01

Primary completion

2027-12-01

Completion

2029-12-01

Publications

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• Background Ying S, Zeng PYF, Fung K, Khan H, Cecchini MJ, MacInnis P, Anderson J, Karimi AH, Al Jawhri M, Pan H, Le N, Joris K, Mymryk JS, Dumeaux V, Barrett JW, Nichols AC, Lin RJ; Canadian Airways Research Group of the Canadian Society of Otolaryngology Collaborative Research Initiative. Effect of Serial Intralesional Steroid Injections on Risk of Recurrence in Idiopathic Subglottic Stenosis. Laryngoscope. 2025 Sep;135(9):3265-3272. doi: 10.1002/lary.32179. Epub 2025 Apr 16.
• Background Ying S, Zeng PYF, Fung K, Khan H, Cecchini MJ, Woo E, Anderson J, MacInnis P, Karimi AH, Al Jawhri M, Pan H, Le N, Joris K, Wen R, Mymryk JS, Inculet R, Dumeaux V, Barrett JW, Nichols AC, Lin RJ; Canadian Airways Research Group of the Canadian Society of Otolaryngology Collaborative Research Initiative. Transcriptomic Features of Recurrence Rates in Idiopathic Subglottic Stenosis. Laryngoscope. 2025 Sep;135(9):3273-3279. doi: 10.1002/lary.32214. Epub 2025 May 6.
• Background Lin RJ, Zeng PYF, Fung K, Khan H, Cecchini MJ, Woo E, Hu A, Anderson J, MacInnis P, Karimi A, Ying S, Al Jawhri M, Lin S, Jarycki L, Shaikh MH, Pan H, Coburn B, Mymryk JS, Inculet R, Barrett JW, Nichols AC; Canadian Airways Research Group of the Canadian Society of Otolaryngology Collaborative Research Initiative. Cohort-level clinical trajectory and molecular landscape of idiopathic subglottic stenosis for precision laryngology-a study of the Canadian Airways Research (CARE) group. EBioMedicine. 2025 Apr;114:105629. doi: 10.1016/j.ebiom.2025.105629. Epub 2025 Mar 5.
• Background Zeng PYF, Lin RJ, Fung K, Khan H, Cecchini MJ, Woo E, Hu A, Anderson J, MacInnis P, Jarycki L, Karimi A, Ying S, Al Jawhri M, Lin S, Shaikh M, Pan H, Coburn B, Mymryk JS, Inculet R, Barrett JW, Nichols AC; Canadian Airways Research Group of the Canadian Society of Otolaryngology Collaborative Research Initiative. Cellular blueprint of healthy and diseased human epiglottis and subglottis-a study of the Canadian Airways Research (CARE) group. EBioMedicine. 2025 Apr;114:105631. doi: 10.1016/j.ebiom.2025.105631. Epub 2025 Mar 5.

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