Everolimus for Tracheal Stenosis

Overseen By Sarah Collins

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Johns Hopkins University

Must not be taking: Corticosteroids, Cytochrome P450 3A inducers

Disqualifiers: Autoimmune disease, Heart failure, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop using corticosteroids (except for low doses), certain antibiotics, antifungals, antivirals, and any drugs that affect the cytochrome P450 3A enzyme, like some anticonvulsants and grapefruit products, at least 7 days before starting everolimus. If you're on immunosuppressive therapy, you must stop it 21 days before the trial.

What data supports the effectiveness of the drug Everolimus for tracheal stenosis?

Everolimus, a drug with antifibrotic effects, has shown promise in reducing fibrosis (scarring) in lung transplant patients and may help with conditions like tracheal stenosis by slowing down the narrowing of airways. Additionally, similar drugs targeting the same pathway have been effective in reducing fibrosis in airway diseases. ^{1 2 3 4 5}

Is everolimus generally safe for human use?

Everolimus is generally considered safe for human use, with most side effects being mild to moderate and manageable. However, it can cause some serious side effects like pneumonitis (lung inflammation) and infections, so monitoring and management are important. ^{1 2 6 7 8}

How does the drug Everolimus differ from other treatments for tracheal stenosis?

Everolimus is unique because it has antifibrotic effects, which means it can help prevent or reduce the formation of scar tissue, a potential benefit for conditions like tracheal stenosis where scar tissue can narrow the airway. Additionally, it is an immunosuppressant, which can help reduce inflammation and immune response, potentially offering a novel approach compared to other treatments. ^{1 2 3 9 10}

What is the purpose of this trial?

This trial is testing the drug everolimus to see if it can reduce the number of surgeries needed for patients with idiopathic Subglottic Stenosis (iSGS), a condition where scar tissue blocks the airway. Everolimus helps by calming the immune system and reducing scar tissue formation. If successful, this could lead to everolimus becoming an approved treatment for iSGS.

Research Team

Alexander Hillel, MD

Principal Investigator

Johns Hopkins School of Medicine

Eligibility Criteria

Adults aged 18-80 with laryngotracheal stenosis, who've had a specific throat surgery, can join this trial. They must understand the study and agree to participate. Key health markers like liver function and kidney function need to be within certain limits. Pregnant women, those with severe lung disease unrelated to their stenosis, recent participants in other drug trials, people with active autoimmune diseases or recent cancers (except some skin cancers), organ transplant recipients on immunosuppressants, and individuals not fully vaccinated against COVID-19 are excluded.

Inclusion Criteria

I have records of when my airway narrowing was diagnosed and my past treatments.

I have been diagnosed with narrowing of the windpipe.

I've had a throat surgery involving scar removal and stretching.

Exclusion Criteria

Participation in any clinical trial within 21 days of bone marrow collection involving an investigational drug or device

You have a known weak immune system.

I have tested positive for HTLV 1 or 2.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive low dose everolimus for 6 weeks after surgical dilation

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Everolimus

Trial Overview The AERO trial is testing an oral tablet called everolimus as a potential treatment for patients with idiopathic Subglottic Stenosis—a condition causing scar-induced airway obstruction—to reduce the number of required surgeries. This proof-of-concept study could pave the way for larger trials if successful.

Participant Groups

Group I: Adjuvant Everolimus After Surgical Dilation Experimental Treatment 1 Intervention

Individuals will take low dose everolimus for 6 weeks after dilation.

Everolimus is already approved in United States, European Union for the following indications:

Approved in United States as Afinitor for:

• Advanced renal cell carcinoma
• Subependymal giant cell astrocytoma
• Progressive neuroendocrine tumors of pancreatic origin
• Advanced hormone receptor-positive, HER2-negative breast cancer
• Tuberous sclerosis complex-associated partial-onset seizures

Approved in European Union as Votubia for:

• Subependymal giant cell astrocytoma
• Renal angiomyolipoma
• Tuberous sclerosis complex-associated partial-onset seizures

Approved in United States as Zortress for:

• Prevention of organ rejection in kidney transplant patients

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Findings from Research

In a study of 65 lung transplant recipients, conversion to everolimus was primarily due to bronchiolitis obliterans syndrome (BOS) and renal insufficiency, with 21% of patients able to eliminate calcineurin inhibitors (CNI) from their regimen.

While renal function improved significantly in patients with renal insufficiency, the effects of everolimus on BOS were inconclusive, as forced expiratory volume (FEV1) remained stable among those with BOS after 12 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective 12-month study of conversion to everolimus in lung transplant recipients. Roman, A., Ussetti, P., Zurbano, F., et al.[2015]

In a study of 10 lung transplant recipients who were converted to everolimus, the drug was found to be effective and safe over a long-term follow-up period, with stable renal function and no rejection episodes reported.

While there were some adverse events, including infections and two cases of neoplasia, the overall results suggest that everolimus can be a viable option for lung transplant patients when used alongside low doses of calcineurin inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term use of everolimus in lung transplant patients. Parada, MT., Alba, A., Sepúlveda, C., et al.[2015]

In a clinical trial with 213 lung transplant patients, everolimus significantly reduced the incidence of efficacy failure (21.8% vs. 33.9% for azathioprine) at 12 months, indicating its effectiveness in slowing the progression of bronchiolitis obliterans syndrome (BOS).

While everolimus showed benefits in reducing acute rejection and decline in lung function at 12 months, it also had a higher rate of treatment discontinuations and serious adverse events, highlighting the need for careful monitoring of patients on this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Everolimus versus azathioprine in maintenance lung transplant recipients: an international, randomized, double-blind clinical trial. Snell, GI., Valentine, VG., Vitulo, P., et al.[2023]

Everolimus is an effective immunosuppressant that inhibits T-lymphocyte proliferation, showing low rates of acute rejection in kidney transplant patients when used with cyclosporine-based immunosuppression.

Recent studies indicate that everolimus may also help prevent allograft vasculopathy in heart transplant patients, highlighting its potential benefits beyond kidney transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with everolimus. Augustine, JJ., Hricik, DE.[2015]

References

1. United States pubmed.ncbi.nlm.nih.gov

A retrospective 12-month study of conversion to everolimus in lung transplant recipients. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

Long-term use of everolimus in lung transplant patients. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

Everolimus versus azathioprine in maintenance lung transplant recipients: an international, randomized, double-blind clinical trial. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Sirolimus-eluting airway stent reduces profibrotic Th17 cells and inhibits laryngotracheal stenosis. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Sirolimus and FK778: a comparison of two anti-proliferative immunosuppressants for prevention of experimental obliterative airway disease. [2014]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Practical management of everolimus-related toxicities in patients with advanced solid tumors. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Experience with everolimus. [2015]

8. United States pubmed.ncbi.nlm.nih.gov

Pneumonitis associated with mammalian target of rapamycin inhibitors in renal transplant recipients: a single-center experience. [2021]

9. France pubmed.ncbi.nlm.nih.gov

A randomized comparison of a durable polymer Everolimus-eluting stent with a bare metal coronary stent: The SPIRIT first trial. [2022]

10. Ireland pubmed.ncbi.nlm.nih.gov

Everolimus-coated tympanostomy tube on rat tympanic membrane. [2015]