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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug everolimus (also known as Afinitor, Votubia, or Zortress) can benefit people with idiopathic subglottic stenosis (iSGS), a condition where scar tissue narrows the airway, making breathing and speaking difficult. The trial aims to determine if everolimus can reduce the number of surgeries needed for this condition. Participants will take a low dose of everolimus for six weeks following a procedure to widen the airway. Those who have previously undergone surgery to remove scar tissue and dilate the airway may be suitable candidates for this trial. As an Early Phase 1 trial, this research focuses on understanding how everolimus works in people with iSGS, offering participants a chance to contribute to groundbreaking treatment insights.

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.

Is there any evidence suggesting that everolimus is likely to be safe for humans?

Research has shown that everolimus is generally safe for people. In a study on idiopathic subglottic stenosis (iSGS), everolimus caused only minor side effects and helped maintain good breathing for 7 weeks. Most side effects are mild to moderate and manageable. However, serious side effects, though rare, can occur. The FDA has already approved everolimus for other uses, indicating a good overall safety record. ^{1 2 3 4}

Why do researchers think this study treatment might be promising?

Most treatments for tracheal stenosis involve surgical procedures like dilation or stenting to physically open up the airway. However, researchers are excited about everolimus because it represents a new approach by using medication to prevent the re-narrowing of the trachea after such procedures. Everolimus is unique as it is an mTOR inhibitor, which means it can potentially reduce inflammation and scar formation in the trachea, addressing the root cause of the narrowing rather than just temporarily expanding the airway. This approach could offer longer-lasting relief and improve the quality of life for patients with tracheal stenosis.

What evidence suggests that everolimus might be an effective treatment for subglottic stenosis?

Research has shown that everolimus, a medication that helps control the immune system, might reduce the need for repeated surgeries in people with idiopathic subglottic stenosis (iSGS). In this trial, participants will receive adjuvant everolimus after surgical dilation. One study found that everolimus could safely increase the time between necessary procedures to open narrowed airways. In other conditions where scar tissue forms, such as fibrosis, everolimus has effectively reduced scar tissue. This suggests it might also help manage scarring in the airways, potentially improving breathing and reducing problems linked to iSGS. While more research is needed, these early findings offer promise for those seeking new treatment options. ^{1 2 3 4 5}

Who Is on the Research Team?

Alexander Hillel, MD

Principal Investigator

Johns Hopkins School of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05153668?cond=%22Tracheal%20Disease%22&intr=%22enzyme%20inhibitors%22&viewType=Table&rank=2

NCT05153668 | Everolimus Trial in Laryngotracheal Stenosis The proposed Adjuvant EveRolimus Outcomes (AERO) trial is proof-of-concept study using the immunosuppressant drug, everolimus, to reduce the number of surgeries ...

2. hopkinsmedicine.org hopkinsmedicine.org/news/articles/2024/11/new-johns-hopkins-study-examines-oral-use-of-everolimus-to-treat-idiopathic-subglottic-stenosis

New Johns Hopkins Study Examines Oral Use of ... Results from this trial suggest that everolimus may be a safe adjuvant therapy that could prolong the dilation interval (time patients have ...

3. withpower.com withpower.com/trial/everolimus-for-tracheal-stenosis-ae029

Everolimus for Tracheal Stenosis · Info for Participants 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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11428025/

Oral Everolimus Following Dilation in Idiopathic Subglottic ... In the fibrosis literature, everolimus has been shown to be effective in reducing scar formation across a variety of fibroproliferative ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1043181023000313

Office based steroid injections for subglottic stenosis As a group they started at a PEF% of 55% and ended their SILSI at a PEF% of 93%. Their most recent PEF% is 92% reflecting the lasting efficacy SILSI offers. As ...