Inhaled Treprostinil for Sarcoidosis

(SAPPHIRE Trial)

Overseen By Ali Ataya, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Florida

Must not be taking: Prostanoids

Disqualifiers: Pregnancy, Left heart disease, others

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

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: Unknown

Duration: 16 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether inhaled treprostinil, a medication for lung conditions, can benefit individuals with lung issues caused by sarcoidosis, a disease that results in small patches of red and swollen tissue. The trial targets those with interstitial lung disease (scarring of lung tissue) and pulmonary hypertension (high blood pressure in the lungs). Participants will begin with a low dose of the inhaled treatment, which may increase if tolerated. It suits individuals already diagnosed with sarcoidosis, experiencing these specific lung problems, and maintaining a stable treatment routine for the past three months. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that any sarcoidosis or oral PAH therapy you are on should be stable for at least three months before screening. If you are on prostanoid therapy, you cannot participate in the trial.

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

Research has shown that inhaled treprostinil is safe for use. Studies with patients who have pulmonary arterial hypertension (PAH) indicate that long-term use of treprostinil is generally well-tolerated. In these studies, patients did not experience severe side effects, and most managed the treatment well, even over extended periods.

The FDA has approved treprostinil for treating PAH, confirming its strong safety record. While some individuals might experience mild side effects like a cough or throat irritation, serious side effects are rare.

These findings suggest that inhaled treprostinil is generally safe, though individual experiences can vary. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sarcoidosis?

Inhaled Treprostinil is unique because it offers a new delivery method for treating sarcoidosis patients with interstitial lung disease and pulmonary hypertension. Unlike standard treatments, which often include oral medications or intravenous infusions, this treatment is inhaled, allowing direct delivery to the lungs. This method not only aims to improve lung function more efficiently but also potentially reduces systemic side effects. Researchers are excited about its potential to provide faster relief and better manage symptoms compared to existing options.

What evidence suggests that inhaled treprostinil might be an effective treatment for sarcoidosis?

Research shows that inhaled treprostinil can improve lung function in individuals with certain lung diseases. Previous studies demonstrated that patients using this treatment walked longer distances in a 6-minute walk test, indicating enhanced exercise capacity. This improvement appeared after just four weeks and became significant by twelve weeks. Inhaled treprostinil is already approved for treating pulmonary arterial hypertension, suggesting potential effectiveness for similar conditions. In this trial, participants with sarcoidosis and interstitial lung disease will receive inhaled treprostinil to assess its safety and effectiveness. The treatment has proven safe and effective, even for patients with multiple health issues. ^{3 4 6 7 8}

Who Is on the Research Team?

Ali Ataya, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for adults with sarcoidosis-associated lung disease and high blood pressure in the lungs. Participants must be able to walk a certain distance, not be pregnant or breastfeeding, have stable health conditions, and agree to use birth control if applicable. Those on certain heart medications or with severe heart issues cannot join.

Inclusion Criteria

Study participant willing and able to provide informed consent

A 6MWT within three months of screening visit of > 100 meters

Negative urine pregnancy test at baseline for females of childbearing potential

Exclusion Criteria

Pregnant patients or those who are actively lactating

Patient not willing to use form of birth control (if applicable) during the study

Inability to undergo 6MWT, RHC, PFTs or CMRI

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive inhaled treprostinil with dose escalations every three days, up to 16 weeks

16 weeks

Regular visits for dose adjustments and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Inhaled Treprostinil

Trial Overview The study tests the effectiveness and safety of inhaling Treprostinil—a medication—in patients who have both sarcoidosis-related lung scarring and pulmonary hypertension (high blood pressure affecting the lungs).

How Is the Trial Designed?

Group I: Study Group Experimental Treatment 1 Intervention

Sarcoidosis patients with interstitial lung disease and precapillary pulmonary hypertension based on right heart catheterization (RHC). All subjects will initiate inhaled treprostinil at a dose of 3 breaths (18 mcg) four times daily. Study drug doses escalations (additional one breath four times daily) can occur every three days with a maximum dosing regimen of up to 12 breaths (72 mcg) four times daily, as clinically tolerated.

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?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

United Therapeutics

Industry 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

In a study of 38 fibrotic sarcoidosis patients, those treated with roflumilast showed a significant reduction in episodes where their lung function (FEV-1) dropped below 90% of their best value, indicating improved respiratory stability.

Patients receiving roflumilast also reported a significant improvement in their quality of life, as measured by the KSQ LUNG questionnaire, compared to those on placebo, suggesting that roflumilast may enhance overall well-being in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Roflumilast (Daliresp®) to reduce acute pulmonary events in fibrotic sarcoidosis: a multi-center, double blind, placebo controlled, randomized clinical trial. Baughman, RP., Judson, MA., Culver, DA., et al.[2022]

Sarcoidosis primarily affects the lungs and is diagnosed through clinical presentation, imaging, and the presence of non-caseating granulomas, with biopsies from superficial lesions recommended for accurate diagnosis.

Corticosteroids are the first-line treatment for lung involvement in sarcoidosis, but half of patients may experience spontaneous resolution, highlighting the need for careful monitoring and personalized treatment strategies, including potential use of immunosuppressive and anti-TNFα drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Lung sarcoidosis: Clinical features and therapeutic issues]. Uzunhan, Y., Jeny, F., Crockett, F., et al.[2017]

Sarcoidosis is a systemic inflammatory condition primarily affecting the lungs, with over 90% of patients showing abnormalities, but many remain asymptomatic or improve without treatment, highlighting the importance of careful initial assessment and regular monitoring.

Oral corticosteroids have been the standard treatment since the 1950s, showing short to medium-term benefits, but the long-term effectiveness remains uncertain, prompting exploration of inhaled steroids and alternative immunosuppressants in management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management strategies for pulmonary sarcoidosis. Coker, RK.[2021]

In a study of eight patients with sarcoidosis-related pulmonary hypertension, short-term treatment with inhaled nitric oxide (iNO) resulted in a significant decrease in pulmonary vascular resistance (PVR) by 31% and mean pulmonary artery pressure (mPAP) by 18%, indicating its efficacy as a pulmonary vasodilator.

Long-term treatment with iNO showed improvements in exercise capacity, as all five patients receiving it had better results on the 6-minute walk test, suggesting potential benefits for ongoing management of pulmonary hypertension in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vasoresponsiveness of sarcoidosis-associated pulmonary hypertension. Preston, IR., Klinger, JR., Landzberg, MJ., et al.[2019]

Refractory pulmonary sarcoidosis is defined by progressive disease despite at least 10 mg of prednisolone for three months, requiring additional treatments due to ineffectiveness or intolerability, and significant impairment of life due to symptoms.

For patients with refractory sarcoidosis, treatment options include second-line agents like methotrexate and infliximab, and newer anti-fibrotic drugs like pirfenidone may also be promising, with lung transplantation considered for those unresponsive to medical therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Refractory pulmonary sarcoidosis - proposal of a definition and recommendations for the diagnostic and therapeutic approach. Korsten, P., Strohmayer, K., Baughman, RP., et al.[2020]

Efzofitimod, a novel biologic targeting neuropilin-2 (NRP2), has shown promise in reducing granulomatous inflammation in sarcoidosis, as demonstrated in preclinical studies with an animal model.

In a dose-escalating trial involving patients with chronic symptomatic pulmonary sarcoidosis, efzofitimod improved quality of life and showed a trend towards reduced use of glucocorticoids while maintaining or improving pulmonary function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efzofitimod: a novel anti-inflammatory agent for sarcoidosis. Baughman, RP., Niranjan, V., Walker, G., et al.[2023]

A systematic review of 15 studies found that nine out of 14 pharmacological interventions significantly improved health-related quality of life (HRQoL) and fatigue in sarcoidosis patients, indicating potential benefits for those with active disease.

Most studies had a high risk of bias, highlighting the need for more rigorous randomized, double-blind, and placebo-controlled trials to better understand the effects of treatments on HRQoL and fatigue in sarcoidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of pharmacological interventions on quality of life and fatigue in sarcoidosis: a systematic review. Vis, R., van de Garde, EMW., Grutters, JC., et al.[2022]

Sarcoidosis is a rare disease that primarily affects the lungs and lymph nodes, but can also impact other organs, making it important to differentiate from other rheumatic diseases during diagnosis.

The main diagnostic procedure involves bronchoscopy with ultrasound-guided fine needle aspiration, and treatment typically starts with cortisone, while methotrexate and azathioprine are effective second-line options, with TNF-neutralizing antibodies considered for third-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Sarcoidosis]. Frye, BC., Schupp, JC., Köhler, TC., et al.[2018]

Citations

1. tyvasohcp.com tyvasohcp.com/ph-ild/efficacy-safety/efficacy/

TYVASO® INCREASE Study Efficacy Patients who took TYVASO saw improvement in 6MWD starting as early as week 4 and reached statistical significance by week 12.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12224286/

Practical Considerations for Managing Patients on Tyvaso ... While comorbidities should be considered, inhaled treprostinil remains safe and effective even in these patients [33, 34]. A recently published ...

3. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2022/214324Orig1s000MedR.pdf

214324Orig1s000 CLINICAL REVIEW(S) - accessdata.fda.gov Treprostinil is a prostacyclin mimetic currently indicated for the treatment of WHO group I pulmonary arterial hypertension (PAH) as an ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1094553923000780

Tyvaso DPI: Drug-device characteristics and patient clinical ... Inhaled treprostinil results in clinical improvements in patients with PAH and PH-ILD, as well as hemodynamic improvement in patients with PAH [21,[25], [26], [ ...

5. tyvaso.com tyvaso.com/pah/about-tyvaso/clinical-findings/

TYVASO® (treprostinil) Clinical Findings and Results In a clinical study, people who added TYVASO to their current PAH medicine walked farther, improving their 6MWD in as soon as 6 weeks.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35514770/

BREEZE: Open-label clinical study to evaluate the safety ... Studies have confirmed the robust benefits and safety of nebulized inhaled treprostinil, but it requires a time investment for nebulizer ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0954611125003816

Long-Term Safety and Efficacy of Treprostinil Dry Powder ... The BREEZE OEP successfully demonstrated the safety of long-term treatment with treprostinil DPI in patients with PAH. Clinical Trial ...

8. resmedjournal.com resmedjournal.com/article/S0954-6111(25)00381-6/fulltext

BREEZE Optional Extension Phase: Long-term safety and ... Long-term use of treprostinil DPI in PAH was safe and may provide clinical stability. Abstract. Introduction. Pulmonary arterial hypertension (PAH) is a rare ...