Inhaled Treprostinil in Sarcoidosis Patients With Pulmonary Hypertension

Study Overview
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Brief Summary
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This study aims to evaluate the efficacy and safety of inhaled treprostinil in subjects with sarcoidosis-associated interstitial lung disease and pulmonary hypertension.

Detailed Description
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Pulmonary sarcoidosis-associated pulmonary hypertension is classified as WHO Group 5 pulmonary hypertension and may occur in anywhere from 5-20% of sarcoidosis patients. Inhaled treprostinil has shown clinical improvements in exercise capacity after 12 weeks of therapy in patients with WHO Group 1 pulmonary hypertension. More recently, there has been interest in using inhaled PAH-specific therapies for the treatment of pulmonary hypertension associated with interstitial lung disease. The investigators believe that those patients with pulmonary hypertension in the setting of sarcoidosis-associated interstitial lung disease are a unique population which may potentially benefit from inhaled, targeted pulmonary arterial hypertension therapy (inhaled treprostinil) while minimizing the adverse effects associated with systemic pulmonary vasodilators. This study aims to evaluate the efficacy and safety of inhaled treprostinil in subjects with sarcoidosis-associated interstitial lung disease and pulmonary hypertension.

Official Title
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An Open-Label Study of Inhaled Treprostinil in Sarcoidosis Patients With Pulmonary Hypertension and Interstitial Lung Disease (SAPPHIRE)

Conditions
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Sarcoidosis, Precapillary Pulmonary Hypertension, Interstitial Lung Disease

Intervention / Treatment
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* Drug: Inhaled Treprostinil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Study participant willing and able to provide informed consent Negative urine pregnancy test at baseline for females of childbearing potential Established diagnosis of sarcoidosis by ATS/ERS/WASOG 1999 Statement on of Sarcoidosis Presence of interstitial lung disease by Scadding Stage IV chest radiograph or extensive fibrosis on chest computed tomography Right heart catheterization within six months of baseline visit showing precapillary pulmonary hypertension (mPAP ≥ 25 mmHg, PCWP ≤ 15 mmHg, and PVR > 3 WU) Patient on stable sarcoidosis therapy for at least three months prior to screening If patients are on oral PAH therapy (PDE5i/SCGS and/or ERA) then dose should be stable for at least three months prior to screening A 6MWT within three months of screening visit of > 100 meters 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 Predicted survival < 6 months Patient on any prostanoid or prostanoid analog therapy Patients with left sided heart disease as defined by either a PCWP > 15 mmHg and/or left ventricular ejection fraction < 40% Use of any investigational drug/device, or participation in any investigational study with therapeutic intent within 30 days prior to randomization.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Group<br>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. | Drug: Inhaled Treprostinil<br>* Inhaled treprostinil causes dilatation of the pulmonary arteries and may help reduce the pulmonary pressures in this studied population. 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.<br>* Other names: pulmonary arterial hypertension (PAH) therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PVR by Right heart catheterization (RHC) | Change in RHC parameter PVR (pulmonary vascular resistance ) | Baseline, Week 16 | 
| mPAP by Right heart catheterization (RHC) | Change in RHC parameter mPAP (mean pulmonary arterial pressure) | Baseline, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 6-Minute Walk Test (6MWT) | change in walk test distance during the study | Baseline, Week 8, Week 16 | 
| Change in Cardiac MRI parameters | Change in Right ventricle ejection fraction, Right ventricular end diastolic ventricle index, right ventricular systolic index | Baseline, Week 16 | 
| Change in Pulmonary Function Testing | Change in FEV1 abd FVC | Baseline, Week 16 | 
| Change in Brain Natriuretic Peptide (BNP) | change in BNP level during the study | Baseline, Week 16 | 
| Change in WHO Functional Class (WHO FC) | change in WHO FC status during the study | Baseline, Week 8, Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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right heart catheterization (RHC), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), pulmonary hypertension (PH), Inhaled treprostinil, Sarcoidosis