Everolimus Trial in Laryngotracheal Stenosis

AERO: Adjuvant EveRolimus Outcomes in Laryngotracheal Stenosis

Subglottic stenosis (obstructing scar in the larynx and trachea) occurs in patients spontaneously (idiopathic), with autoimmune disease, and after long-term breathing tube placement and can result in communication disability and high mortality rates due to the obstructed airway. The proposed Adjuvant EveRolimus Outcomes (AERO) trial is proof-of-concept study using the immunosuppressant drug, everolimus, to reduce the number of surgeries for patients with idiopathic Subglottic Stenosis (iSGS). Success with the AERO trial will allow for everolimus to be used in subsequent larger trials of participants with laryngotracheal stenosis and could lead to everolimus being the first FDA approved medical treatment for iSGS.

Study Overview

• Status: Completed
• Conditions: Idiopathic Subglottic Tracheal Stenosis
• Intervention / Treatment: Drug: Everolimus Oral Tablet

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Outpatient Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Current diagnosis of laryngotracheal stenosis
• Patient age 18 - 80 years old
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
• Serum total bilirubin and Serum Glutamic Pyruvic Transaminase (SGPT)/(ALT) < 2.0 times the upper limit of normal;
• Serum creatinine < 2.0 mg/dL;
• The patient must be able to comprehend and have signed the informed consent.
• The patient must have documentation of their date of laryngotracheal stenosis diagnosis and prior medical/surgical history.
• Participants must have also had a prior suspension microlaryngoscopy with endoscopic excision of scar and balloon dilation procedure prior to study entry

Exclusion Criteria:

• Use of corticosteroids (glucocorticoids) within 7 days of everolimus administration (except physiologic dose equivalent)
• Infection requiring treatment with antibiotics, antifungal, or antiviral agents within 7 days of registration
• Participation in any clinical trial within 21 days of bone marrow collection involving an investigational drug or device
• History of malignancy within five years of registration, except adequately treated basal or squamous cell skin cancer
• History of an autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus) requiring active systemic treatment. Hypothyroidism without evidence of Grave's disease or Hashimoto's thyroiditis is permitted.
• Human T-cell Lymphotropic Virus type 1 (HTLV-1) or type 2 (HTLV-2)
• New York Heart Association (NYHA) class II-IV heart failure within the past 6 months
• History of organ transplant with use of immunosuppression
• Current use of immunosuppression
• Contraindication or documented intolerance to everolimus
• Women of childbearing potential who are not on highly effective contraception or abstinent for at least 30 days. Highly effective contraception includes at least two forms of concurrent contraception (Condoms, oral contraceptives, intrauterine devices, contraceptive implants).
• Women who are pregnant or breastfeeding, or wishing to become pregnant are excluded from this study
• Current use of cytochrome P450 3A inducers (such as some anticonvulsants, rifampin, isoniazid, St. John's wort).
• Current use of cytochrome P450 3A inhibitors (such as azole antifungals, nondihydropyridine calcium channel blockers, some macrolide antibiotics, grapefruit) can result in significant interactions
• Baseline proteinuria as defined by urine dipstick analysis
• History of angioedema
• Baseline/continued use of drugs known to be associated with angioedema including angiotensin converting enzyme inhibitors
• Significant pulmonary disease independent of laryngotracheal stenosis as defined by and forced expiratory volume at one second (FEV1)/forced vital capacity (FVC) < 10% of the expected value for the patient's age.
• Evidence of a COVID-19 infection including anosmia, upper respiratory symptoms or positive test result within the 30 days prior of trial participation.
• Patients who are not fully vaccinated for COVID 19 for at least 4 weeks prior to study entry
• Immunosuppressive therapy within previous 21 days or expected need for immunosuppressive therapy for the duration of the study
• Known immunodeficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adjuvant Everolimus After Surgical Dilation; Individuals will take low dose everolimus for 6 weeks after dilation.	Drug: Everolimus Oral Tablet; Everolimus 1.5mg by mouth daily will be given for 42 days after dilation surgery.; Other Names: Zortress

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Peak Expiratory flow in patients with Laryngotracheal Stenosis	Change in Peak Expiratory flow (L/min) in patients with Laryngotracheal Stenosis will be assessed.	Baseline, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 1 year, 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dilation interval (time between surgery)	Dilation interval (time between surgery) in months will be assessed.	Up to 2 years
Change in Voice-related Quality of Life Score	Number scale of 0-100	Baseline, 1 month, 2 months, 3 months, 6 months, 1 year, 2 years
Change in Eating Assessment Tool (EAT-10) Swallow Quality of Life Score	Number scale of 0-40	Baseline, 1 month, 2 months, 3 months, 6 months, 1 year, 2 years
Change in 12-Item Short Form (SF-12) Survey Global Quality of Life Score	Number scale of 0-100	Baseline, 1 month, 2 months, 3 months, 6 months, 1 year, 2 years
Change in lumen surface area	CT Neck will be used to assess change in lumen surface area in millimeters squared (mm^2).	Baseline and 6 months
Change in Clinical Chronic Obstructive Pulmonary Disease (COPD) Questionnaire Quality of Life Score	Number scale of 0-6	Baseline, 1 month, 2 months, 3 months, 6 months, 1 year, 2 years

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Alexander Hillel, MD, Johns Hopkins School of Medicine

Publications and helpful links

General Publications

• So RJ, Collins SL, Collins S, Mafla L, Chan-Li Y, Lina I, Gelbard A, Motz KM, Hillel AT. Oral Everolimus Following Dilation in Idiopathic Subglottic Stenosis: A Phase 1 Nonrandomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2024 Nov 1;150(11):1029-1033. doi: 10.1001/jamaoto.2024.2886.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2022
• Primary Completion (Actual): October 23, 2025
• Study Completion (Actual): October 23, 2025

Study Registration Dates

• First Submitted: November 29, 2021
• First Submitted That Met QC Criteria: November 29, 2021
• First Posted (Actual): December 10, 2021

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Immunosuppression; Everolimus; Tracheal Stenosis
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Tracheal Diseases; Tracheal Stenosis; Idiopathic subglottic tracheal stenosis; Organic Chemicals; Macrolides; Lactones; Sirolimus; Everolimus
• Other Study ID Numbers: IRB00284589

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No