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.

Conditions

• Idiopathic Subglottic Stenosis
• Subglottic Stenosis (SGS)

Interventions

DRUG

Pirfenidone 267 MG [Esbriet]

Oral 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.

DRUG

Placebo

Oral 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.

Sponsors & Collaborators

• Unity Health Toronto

  collaborator OTHER

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-12-01

Primary Completion

2027-12-01

Completion

2029-12-01

Countries

• Canada

Study Locations