Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis

(TETON Trial)

Recruiting in Palo Alto (17 mi)

+110 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: United Therapeutics

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

Study RIN-PF-301 is designed to evaluate the superiority of inhaled treprostinil against placebo for the change in absolute forced vital capacity (FVC) from baseline to Week 52.

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.

What data supports the idea that Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis is an effective treatment?

The available research shows that inhaled treprostinil may help improve lung function and reduce worsening of lung disease in patients with idiopathic pulmonary fibrosis. Although the studies mainly focus on its use for other lung conditions, such as pulmonary hypertension, the positive effects seen in those conditions suggest it could be beneficial for idiopathic pulmonary fibrosis as well. Additionally, the drug's ability to improve lung capacity and its antifibrotic properties, which help prevent lung tissue from becoming scarred, support its potential effectiveness for this condition. ^{1 2 3 4 5}

What safety data is available for inhaled treprostinil?

The provided research does not directly address the safety data for inhaled treprostinil in the context of idiopathic pulmonary fibrosis. However, it mentions the use of the Tyvaso Inhalation System for delivering treprostinil, which is approved for pulmonary arterial hypertension. The studies focus on the delivery methods and feasibility of using different nebulizers, but do not provide specific safety outcomes or data related to idiopathic pulmonary fibrosis. ^{6 7 8 9 10}

Is the drug Inhaled Treprostinil a promising treatment for Idiopathic Pulmonary Fibrosis?

Yes, Inhaled Treprostinil shows promise as a treatment for Idiopathic Pulmonary Fibrosis. It has been linked to improvements in lung function and fewer lung disease flare-ups. It also has potential antifibrotic effects, which means it might help reduce lung scarring. Additionally, it is easy to use with a portable inhaler, making it convenient for patients. ^{1 2 3 11 12}

Research Team

Eligibility Criteria

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.

Treatment Details

Interventions

• Inhaled Treprostinil (Prostacyclin Analogue)
• Placebo (Drug)
• Treprostinil Ultrasonic Nebulizer (Device)

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.

Participant Groups

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

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Tyvaso DPI: Drug-device characteristics and patient clinical considerations. [2023]

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

Treprostinil to reverse pulmonary hypertension associated with idiopathic pulmonary fibrosis as a bridge to single-lung transplantation. [2017]

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

Real-world use of inhaled treprostinil for lung disease-pulmonary hypertension: A protocol for patient evaluation and prescribing. [2023]

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

A Comprehensive Review of Treprostinil Pharmacokinetics via Four Routes of Administration. [2018]

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

Inhaled Treprostinil Drug Delivery During Mechanical Ventilation and Spontaneous Breathing Using Two Different Nebulizers. [2018]

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

In vitro delivery of aerosolized treprostinil via modern mechanical ventilation. [2017]

8. New Zealand 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. [2022]

9. England 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. [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

[Treatment of pulmonary fibrosis. New substances and new interventions]. [2021]

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

Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease. [2021]

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

Comparative bioavailability of inhaled treprostinil administered as LIQ861 and Tyvaso® in healthy subjects. [2021]