Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis

(TETON-1 Trial)

Not currently recruiting at 116 trial locations

Overseen By Shilpa Johri, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 3

Sponsor: United Therapeutics

Must be taking: Pirfenidone, Nintedanib

Must not be taking: Prostacyclin, Endothelin antagonists

Disqualifiers: Pregnancy, Obstructive airway, Cardiac disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 6

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether inhaled treprostinil, a medication for pulmonary arterial hypertension, can improve lung function in people with idiopathic pulmonary fibrosis (IPF). IPF causes lung scarring and breathing difficulties. Researchers aim to determine if this treatment surpasses a placebo in increasing the amount of air participants can exhale after a deep breath over a year. The trial includes two groups: one receives the actual treatment, and the other receives a placebo. Individuals diagnosed with IPF, experiencing breathing difficulties, and on stable doses of certain other IPF medications may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for this trial?

The trial requires that you stop certain medications before starting. If you're on pirfenidone or nintedanib, you must be on a stable dose for at least 30 days before the trial. You cannot use both together. Some medications like azathioprine, cyclosporine, and others must be stopped 30 to 60 days before the trial. Check with the trial team for specifics.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting, such as specific PAH-approved therapies and some immunosuppressants, within a specified time before the trial begins. However, if you are on pirfenidone or nintedanib, you must continue on a stable dose for at least 30 days before the trial starts.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that inhaled treprostinil is generally well-tolerated. Previous studies indicate its safety is comparable to similar treatments, with side effects resembling those observed in other studies of this medication type.

One study compared inhaled treprostinil to a placebo and found it reduced the risk of the condition worsening by 39%. This finding suggests the treatment is effective and safe, with no major adverse effects. Additionally, improvements in lung function have been observed in patients with similar lung conditions, further supporting its safety.

Overall, existing evidence suggests that inhaled treprostinil is safe for use, with typically manageable side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for idiopathic pulmonary fibrosis?

Unlike the standard treatments for idiopathic pulmonary fibrosis, which often include antifibrotic medications like pirfenidone and nintedanib, inhaled treprostinil offers a unique approach by targeting the pulmonary blood vessels. This treatment is delivered directly to the lungs through an ultrasonic nebulizer, allowing for direct action on the affected areas. Researchers are excited about inhaled treprostinil because it could improve blood flow and oxygen delivery in the lungs, potentially alleviating symptoms and enhancing quality of life for patients with this challenging condition.

What evidence suggests that inhaled treprostinil might be an effective treatment for idiopathic pulmonary fibrosis?

In this trial, participants will receive either inhaled treprostinil or a placebo. Studies have shown that inhaled treprostinil can improve lung function by increasing lung capacity. Research indicates it also reduces the risk of worsening by about 39% compared to a placebo. Previous studies demonstrated that inhaled treprostinil helped patients with lung diseases like pulmonary hypertension by managing symptoms and reducing flare-ups. Although not all results are statistically significant, trends suggest it may help treat idiopathic pulmonary fibrosis (IPF), a serious lung condition. Overall, initial findings are promising for its use in improving lung health in such conditions. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

Adults over 40 with Idiopathic Pulmonary Fibrosis (IPF) confirmed by HRCT, having an FVC ≥45% predicted. They must not be pregnant or breastfeeding and agree to use contraception. Participants can't have severe obstructive airway disease, recent heart attacks, uncontrolled cardiac disease, or have used certain IPF treatments recently.

Inclusion Criteria

In the opinion of the Investigator, the subject is able to communicate effectively with study personnel, and is considered reliable, willing, and likely to be cooperative with protocol requirements, including attending all study visits.

I have been on a stable dose of either pirfenidone or nintedanib for over 30 days, but not both.

I am not pregnant or breastfeeding and will use two forms of birth control during the study.

Exclusion Criteria

I have taken medication for pulmonary arterial hypertension in the last 60 days.

I need more than 10 liters per minute of oxygen to breathe normally when resting.

I have not had a heart attack in the last 6 months or unstable chest pain in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive inhaled treprostinil or placebo for 52 weeks, with dose titration as tolerated

52 weeks

6 visits (in-person) at Weeks 4, 8, 16, 28, 40, and 52

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term after completing the main study

What Are the Treatments Tested in This Trial?

Interventions

• Inhaled Treprostinil
• Placebo
• Treprostinil Ultrasonic Nebulizer

Trial Overview

The trial is testing inhaled treprostinil delivered via a nebulizer against a placebo to see if it improves lung function measured by forced vital capacity (FVC) after one year of treatment in patients with IPF.

How Is the Trial Designed?

Group I: Inhaled Treprostinil Experimental Treatment 2 Interventions

Treprostinil for inhalation solution (0.6 mg/mL) delivered via an ultrasonic nebulizer which emits a dose of approximately 6 mcg per breath. Inhaled QID and titrated up to a target of 12 breaths QID or until the subject reaches their maximum clinically tolerated dose.

Group II: Placebo Placebo Group 2 Interventions

Matching placebo inhaled using an ultrasonic nebulizer QID

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

Approved in United States as Tyvaso for:

• Pulmonary arterial hypertension (PAH)
• Pulmonary hypertension associated with interstitial lung disease (PH-ILD)

Approved in European Union as Tyvaso for:

• Pulmonary arterial hypertension (PAH)
• Pulmonary hypertension associated with interstitial lung disease (PH-ILD)

Who Is Running the Clinical Trial?

United Therapeutics

Lead Sponsor

Trials

112

Recruited

14,500+

Dr. Martine Rothblatt

United Therapeutics

Chief Executive Officer since 1996

PhD in Medical Ethics from the Royal London College of Medicine and Dentistry, JD and MBA from UCLA

Dr. Michael Benkowitz

United Therapeutics

Chief Medical Officer since 2023

MD from Harvard Medical School

Published Research Related to This Trial

The TETON programme is a phase 3 clinical trial consisting of two 52-week studies involving 792 patients with idiopathic pulmonary fibrosis (IPF) to evaluate the efficacy of inhaled treprostinil, focusing on changes in forced vital capacity (FVC) as the primary endpoint.

Inhaled treprostinil is being investigated due to its potential antifibrotic effects and previous positive outcomes in related lung conditions, with secondary endpoints including time to clinical worsening and overall survival, ensuring a comprehensive assessment of its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study design and rationale for the TETON phase 3, randomised, controlled clinical trials of inhaled treprostinil in the treatment of idiopathic pulmonary fibrosis. Nathan, SD., Behr, J., Cottin, V., et al.[2022]

Inhaled treprostinil significantly improved exercise capacity in patients with pulmonary hypertension due to interstitial lung disease, with an average increase of 31.12 meters in the 6-minute walk test compared to placebo after 16 weeks.

The treatment also led to a notable reduction in NT-proBNP levels, indicating improved heart function, and resulted in fewer patients experiencing clinical worsening compared to the placebo group, suggesting it is a promising option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease. Waxman, A., Restrepo-Jaramillo, R., Thenappan, T., et al.[2021]

The IFIGENIA trial demonstrated that N-acetylcysteine, when used alongside prednisone and azathioprine, significantly slowed the decline in lung function in patients with idiopathic pulmonary fibrosis over 12 months.

Pirfenidone is the first approved antifibrotic drug for idiopathic pulmonary fibrosis in the EU, showing efficacy in slowing lung function decline and reducing disease progression in over 1,100 patients across four clinical trials, though it may cause side effects like gastrointestinal discomfort and skin reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of pulmonary fibrosis. New substances and new interventions]. Costabel, U., Bonella, F.[2021]

LIQ861, a dry-powder formulation of treprostinil, shows comparable bioavailability to the nebulized Tyvaso® inhalation solution, with exposure parameters indicating similar effectiveness in delivering the medication to patients with pulmonary arterial hypertension (PAH).

Both LIQ861 and Tyvaso® were well tolerated by participants, suggesting that LIQ861 offers a safe and convenient alternative for PAH patients, allowing for effective treatment in just 1 to 2 breaths.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative bioavailability of inhaled treprostinil administered as LIQ861 and Tyvaso® in healthy subjects. Roscigno, RF., Vaughn, T., Parsley, E., et al.[2021]

The study established a reliable in vitro method for delivering treprostinil, a treatment for pulmonary arterial hypertension, through a ventilator circuit, achieving a controlled dose of 54 μg in just 29 seconds.

The method demonstrated that the AeroTech II nebulizer could effectively deliver aerosolized treprostinil with consistent dosing across various breathing patterns, highlighting the importance of precise nebulization conditions for optimal drug delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro delivery of aerosolized treprostinil via modern mechanical ventilation. Patel, RB., Smaldone, GC., Cuccia, AD., et al.[2017]

Intravenous treprostinil was successfully used to manage severe pulmonary hypertension in an elderly patient with idiopathic pulmonary fibrosis, highlighting its potential as a bridging therapy before lung transplantation.

This case suggests that treprostinil may improve outcomes for patients with idiopathic pulmonary fibrosis and concurrent pulmonary hypertension, which typically have poor prognoses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treprostinil to reverse pulmonary hypertension associated with idiopathic pulmonary fibrosis as a bridge to single-lung transplantation. Saggar, R., Shapiro, SS., Ross, DJ., et al.[2017]

The study found that the vibrating mesh nebulizer is an effective alternative to the Tyvaso Inhalation System for delivering inhaled treprostinil, with similar fine particle fractions and often greater inhaled mass across various age models (neonatal, pediatric, and adult).

In particular, using the vibrating mesh nebulizer with high-frequency oscillatory ventilation in neonatal and pediatric models resulted in higher delivery of treprostinil, which could lead to higher than expected dosages for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled Treprostinil Drug Delivery During Mechanical Ventilation and Spontaneous Breathing Using Two Different Nebulizers. Parker, DK., Shen, S., Zheng, J., et al.[2018]

In a study of 698 severe asthma patients, 35.9% were treated with long-acting muscarinic antagonists (LAMA), with tiotropium bromide respimat (TBR) being the most common, indicating its potential underuse in severe asthma management.

Patients using LAMA, including TBR, exhibited more severe asthma characteristics, such as higher exacerbation rates, poorer lung function, and a greater prevalence of bronchiectasis, highlighting the need for better treatment strategies in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequency of Tiotropium Bromide Use and Clinical Features of Patients with Severe Asthma in a Real-Life Setting: Data from the Severe Asthma Network in Italy (SANI) Registry. Puggioni, F., Brussino, L., Canonica, GW., et al.[2022]

AZD9164, an inhaled long-acting muscarinic antagonist, showed no safety or tolerability issues in healthy subjects at doses up to 2800 μg, confirming its bronchodilator effect.

However, both healthy subjects and COPD patients experienced a transient drop in FEV1 shortly after inhalation, indicating a potential paradoxical bronchoconstriction that warrants careful monitoring of lung function after dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transient paradoxical bronchospasm associated with inhalation of the LAMA AZD9164: analysis of two Phase I, randomised, double-blind, placebo-controlled studies. Jorup, C., Bengtsson, T., Strandgården, K., et al.[2021]

In a study evaluating the use of inhaled treprostinil for pulmonary hypertension in interstitial lung disease, only 30% of the 10 patients assessed were ultimately prescribed the medication, highlighting the prevalence of misdiagnosis in this population.

The study emphasizes the need for standardized protocols to assess the long-term effectiveness of inhaled treprostinil in real-world clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world use of inhaled treprostinil for lung disease-pulmonary hypertension: A protocol for patient evaluation and prescribing. Johnson, SW., Finlay, L., Mathai, SC., et al.[2023]

Treprostinil is an effective treatment for pulmonary arterial hypertension (PAH) and is available in three formulations: intravenous/subcutaneous (Remodulin®), inhaled (Tyvaso®), and oral (Orenitram®).

Pharmacokinetic studies in both healthy volunteers and PAH patients provide important insights that can help clinicians make informed decisions about the most suitable route of administration for individual patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comprehensive Review of Treprostinil Pharmacokinetics via Four Routes of Administration. Kumar, P., Thudium, E., Laliberte, K., et al.[2018]

Tyvaso DPI is a portable, breath-powered inhaler that delivers treprostinil for treating pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease, offering a passive administration method that enhances patient compliance.

In clinical studies, Tyvaso DPI demonstrated similar drug exposure and safety profiles to nebulized treprostinil, with a low incidence of adverse events and high patient satisfaction, making it a suitable option for patients seeking a convenient and effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tyvaso DPI: Drug-device characteristics and patient clinical considerations. McEvoy, C., Argula, R., Sahay, S., et al.[2023]

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