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.
Adults 18-65 years of age
Confirmed diagnosis of idiopathic subglottic stenosis (iSGS)
History of at least 2 endoscopic dilations within the past 12 months or -Receiving regular intralesional steroid injections as part of iSGS management (every 3 months)
Clinically stable at enrollment (no acute infection or active inflammation)
Subglottic stenosis due to another identifiable cause (e.g., intubation, granulomatosis with polyangiitis, malignancy)
Known hypersensitivity or allergic reaction to pirfenidone or any component of its formulation
Severe hepatic impairment or active liver disease (AST or ALT above the upper limit of normal)
Severe renal impairment or requirement for dialysis
Parallel
Pirfenidone 267 MG [Esbriet]
DrugOral pirfenidone administered in tablet form as systemic antifibrotic therapy for idiopathic subglottic stenosis. Participants assigned to the experimental arm will follow a standard titration regimen: 801 mg/day (267 mg three times daily) during Week 1, 1,602 mg/day (534 mg three times daily) during Week 2, and 2,403 mg/day (801 mg three times daily) from Week 3 through Week 52, as tolerated. Doses are taken with food to reduce gastrointestinal side effects. Pirfenidone is given in addition to standardized intralesional steroid injections as part of protocolized airway management.
Placebo
DrugOral placebo tablets formulated to be visually identical to pirfenidone capsules, including appearance, packaging, and dosing schedule. Participants assigned to the placebo comparator arm will receive placebo using the same titration and maintenance schedule as the pirfenidone arm (three times daily with food for 52 weeks). Placebo is given in addition to standardized intralesional steroid injections as part of protocolized airway management, to allow blinded comparison with active pirfenidone treatment.
Incidence and severity of treatment-emergent adverse events over 52 weeks
Incidence and severity of treatment-emergent adverse events, including events leading to dose modification or discontinuation and protocol-defined lab abnormalities, graded using CTCAE, over 52 weeks of treatment.
Time to first dilation
Time from randomization to first endoscopic airway dilation performed for clinically significant recurrent subglottic stenosis, comparing pirfenidone with placebo.
Change in peak expiratory flow
Change from baseline in peak expiratory flow at scheduled study visits, comparing pirfenidone with placebo.
Change in Dyspnea Index Score
Change from baseline in Dyspnea Index scores at scheduled visits to assess breathlessness.
Change in Voice Handicap Index (VHI)
Change from baseline in Voice Handicap Index scores at scheduled visits to assess voice-related quality of life.
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London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Lead sponsor
Unity Health Toronto
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
