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

NCT07654517 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: 129042
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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)

Keywords

Subglottic Stenosis; Idiopathic Subglottic stenosis; Airway Fibrosis; Pirfenidone

Outcome Measures

Primary Outcomes (1)

• 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.

  From first dose of study through week 52 of treatment.

Secondary Outcomes (4)

• Time to first dilation

  From randomization through end of study follow-up, up to 24 months.

• Change in peak expiratory flow

  Baseline and approximately every 3 months during the 52 week treatment period.

• Change in Dyspnea Index Score

  Baseline and approximately every 3 months during the 52-week treatment and every followup appointment during the second year.

• Change in Voice Handicap Index (VHI)

  Baseline and approximately every 3 months during the 52-week treatment period and every follow up appointment during the followup period in the second year.

Study Arms (2)

Pirfenidone plus standardized intralesional steroid therapy

EXPERIMENTAL

Participants in this arm will receive oral pirfenidone in addition to standardized intralesional steroid injections for idiopathic subglottic stenosis. Pirfenidone will be titrated from 801 mg/day in Week 1 to 1,602 mg/day in Week 2, then to a maintenance dose of 2,403 mg/day (801 mg three times daily) from Week 3 through Week 52, as tolerated. Study drug will be taken with food to reduce gastrointestinal side effects. All participants will continue to receive protocolized intralesional steroid injections as part of their usual airway management. Participants will be followed during treatment and for an additional post-treatment follow-up period to assess safety, tolerability, and preliminary efficacy.

Drug: Pirfenidone 267 MG [Esbriet]

Placebo plus standardized intralesional steroid therapy

PLACEBO COMPARATOR

Participants in this arm will receive an oral placebo in addition to standardized intralesional steroid injections for idiopathic subglottic stenosis. The placebo capsules will be identical in appearance and dosing schedule to pirfenidone, including titration over the first 2 weeks and maintenance dosing three times daily with food through Week 52. All participants will continue to receive protocolized intralesional steroid injections as part of their usual airway management. Participants will be followed during treatment and for an additional post-treatment follow-up period to assess safety, tolerability, and to compare outcomes with the pirfenidone arm.

Drug: Placebo

Interventions

Pirfenidone 267 MG [Esbriet] DRUG

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.

Pirfenidone plus standardized intralesional steroid therapy

Placebo DRUG

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.

Placebo plus standardized intralesional steroid therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Adequate liver and renal function on screening laboratory tests
• Willing and able to comply with study procedures, visits, and follow-up
• Ability to provide written informed consent
• For participants of childbearing potential: negative pregnancy test and agreement to use effective contraception during treatment and for the protocol-specified period after the last dose

You may not qualify if:

• 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
• Concurrent use of fluvoxamine
• Use of high-dose ciprofloxacin or other strong CYP1A2 inhibitors where dose adjustment is not feasible
• Current smoking or unwillingness to abstain from smoking during treatment
• Pregnant or breastfeeding individuals
• Clinically significant comorbid illness that could increase risk or confound results (e.g., advanced cardiac, pulmonary, or autoimmune disease)
• History of photosensitivity disorders or inability to adhere to sun protection precautions
• Participation in another investigational clinical trial within the previous 30 days
• Any condition that, in the investigator's judgment, would interfere with safety monitoring, adherence, or study assessments

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead
• Unity Health Toronto: collaborator

Study Sites (1)

Schulich School of Medicine and Dentistry

London, Ontario, N6A 4L6, Canada

Location

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MeSH Terms

Conditions

Idiopathic subglottic tracheal stenosis

Interventions

pirfenidone

Central Study Contacts

Halema Khan, PhD

CONTACT

519-685-8500; halema.khan@lhsc.on.ca

Anthony Nichols, MD, MD

CONTACT

519-685-8500; anthony.nichols@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind, placebo-controlled trial in which participants, care providers, investigators, and outcomes assessors are masked to treatment allocation. Pirfenidone and placebo capsules are identical in appearance, packaging, and dosing schedule. Unblinding will occur only if required for the clinical management of a serious adverse event or after database lock and final analysis.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This is a multi-centre, randomized, double-blind, placebo-controlled Phase I trial using a parallel-group design. Adults with idiopathic subglottic stenosis will be assigned in a 1:1 ratio to receive oral pirfenidone plus standardized intralesional steroid injections or matching placebo plus standardized intralesional steroid injections for 52 weeks. Participants remain in their assigned treatment arm for the full treatment period, followed by post-treatment follow-up.

Study Record Dates

• First Submitted: June 12, 2026
• First Posted: June 17, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2029
• Last Updated: June 17, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: De-identified individual participant data (IPD) will be made available beginning approximately 12 months after completion of data collection for the primary outcome and publication of the main results, and will remain available for at least 5 years thereafter. The final study protocol, statistical analysis plan, and template informed consent form may be shared earlier, prior to completion of data analysis, to facilitate collaboration and potential participation of additional sites.
• Access Criteria: The protocol, statistical analysis plan, and template informed consent form may be shared with investigators at academic or healthcare institutions who express interest in collaboration or site participation, following institutional approvals and, where applicable, confidentiality agreements. After primary results are published, de-identified IPD and supporting documents will be available to qualified researchers with methodologically sound proposals that address scientifically valid questions. Requests should include a brief research proposal and data security plan and will be reviewed by the study team and institutional oversight as required. Approved requestors will sign a data use agreement specifying permitted uses, data security and confidentiality requirements, prohibition of re-identification, and conditions for publication and further sharing. Data and documents will be provided via secure, access-controlled electronic transfer or a trusted data repository.

Locations

CA (1)