<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03814317</url>
  </required_header>
  <id_info>
    <org_study_id>OCR19684</org_study_id>
    <secondary_id>20192572</secondary_id>
    <nct_id>NCT03814317</nct_id>
  </id_info>
  <brief_title>Inhaled Treprostinil in Sarcoidosis Patients With Pulmonary Hypertension</brief_title>
  <acronym>SAPPHIRE</acronym>
  <official_title>An Open-Label Study of Inhaled Treprostinil in Sarcoidosis Patients With Pulmonary Hypertension and Interstitial Lung Disease (SAPPHIRE)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Florida</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>United Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Florida</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to evaluate the efficacy and safety of inhaled treprostinil in subjects with&#xD;
      sarcoidosis-associated interstitial lung disease and pulmonary hypertension.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pulmonary sarcoidosis-associated pulmonary hypertension is classified as WHO Group 5&#xD;
      pulmonary hypertension and may occur in anywhere from 5-20% of sarcoidosis patients. Inhaled&#xD;
      treprostinil has shown clinical improvements in exercise capacity after 12 weeks of therapy&#xD;
      in patients with WHO Group 1 pulmonary hypertension. More recently, there has been interest&#xD;
      in using inhaled PAH-specific therapies for the treatment of pulmonary hypertension&#xD;
      associated with interstitial lung disease.&#xD;
&#xD;
      The investigators believe that those patients with pulmonary hypertension in the setting of&#xD;
      sarcoidosis-associated interstitial lung disease are a unique population which may&#xD;
      potentially benefit from inhaled, targeted pulmonary arterial hypertension therapy (inhaled&#xD;
      treprostinil) while minimizing the adverse effects associated with systemic pulmonary&#xD;
      vasodilators. This study aims to evaluate the efficacy and safety of inhaled treprostinil in&#xD;
      subjects with sarcoidosis-associated interstitial lung disease and pulmonary hypertension.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 30, 2020</start_date>
  <completion_date type="Anticipated">October 29, 2023</completion_date>
  <primary_completion_date type="Anticipated">October 29, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_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.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PVR by Right heart catheterization (RHC)</measure>
    <time_frame>Baseline, Week 16</time_frame>
    <description>Change in RHC parameter PVR (pulmonary vascular resistance )</description>
  </primary_outcome>
  <primary_outcome>
    <measure>mPAP by Right heart catheterization (RHC)</measure>
    <time_frame>Baseline, Week 16</time_frame>
    <description>Change in RHC parameter mPAP (mean pulmonary arterial pressure)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in 6-Minute Walk Test (6MWT)</measure>
    <time_frame>Baseline, Week 8, Week 16</time_frame>
    <description>change in walk test distance during the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Cardiac MRI parameters</measure>
    <time_frame>Baseline, Week 16</time_frame>
    <description>Change in Right ventricle ejection fraction, Right ventricular end diastolic ventricle index, right ventricular systolic index</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Pulmonary Function Testing</measure>
    <time_frame>Baseline, Week 16</time_frame>
    <description>Change in FEV1 abd FVC</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Brain Natriuretic Peptide (BNP)</measure>
    <time_frame>Baseline, Week 16</time_frame>
    <description>change in BNP level during the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in WHO Functional Class (WHO FC)</measure>
    <time_frame>Baseline, Week 8, Week 16</time_frame>
    <description>change in WHO FC status during the study</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Sarcoidosis</condition>
  <condition>Precapillary Pulmonary Hypertension</condition>
  <condition>Interstitial Lung Disease</condition>
  <arm_group>
    <arm_group_label>Study Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sarcoidosis patients with interstitial lung disease and precapillary pulmonary hypertension based on right heart catheterization (RHC).&#xD;
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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Inhaled Treprostinil</intervention_name>
    <description>Inhaled treprostinil causes dilatation of the pulmonary arteries and may help reduce the pulmonary pressures in this studied population.&#xD;
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.</description>
    <arm_group_label>Study Group</arm_group_label>
    <other_name>Tyvaso®</other_name>
    <other_name>pulmonary arterial hypertension (PAH) therapy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Study participant willing and able to provide informed consent&#xD;
&#xD;
          -  Negative urine pregnancy test at baseline for females of childbearing potential&#xD;
&#xD;
          -  Established diagnosis of sarcoidosis by ATS/ERS/WASOG 1999 Statement on of Sarcoidosis&#xD;
&#xD;
          -  Presence of interstitial lung disease by Scadding Stage IV chest radiograph or&#xD;
             extensive fibrosis on chest computed tomography&#xD;
&#xD;
          -  Right heart catheterization within six months of baseline visit showing precapillary&#xD;
             pulmonary hypertension (mPAP ≥ 25 mmHg, PCWP ≤ 15 mmHg, and PVR &gt; 3 WU)&#xD;
&#xD;
          -  Patient on stable sarcoidosis therapy for at least three months prior to screening&#xD;
&#xD;
          -  If patients are on oral PAH therapy (PDE5i/SCGS and/or ERA) then dose should be stable&#xD;
             for at least three months prior to screening&#xD;
&#xD;
          -  A 6MWT within three months of screening visit of &gt; 100 meters&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant patients or those who are actively lactating&#xD;
&#xD;
          -  Patient not willing to use form of birth control (if applicable) during the study&#xD;
&#xD;
          -  Inability to undergo 6MWT, RHC, PFTs or CMRI&#xD;
&#xD;
          -  Predicted survival &lt; 6 months&#xD;
&#xD;
          -  Patient on any prostanoid or prostanoid analog therapy&#xD;
&#xD;
          -  Patients with left sided heart disease as defined by either a PCWP &gt; 15 mmHg and/or&#xD;
             left ventricular ejection fraction &lt; 40%&#xD;
&#xD;
          -  Use of any investigational drug/device, or participation in any investigational study&#xD;
             with therapeutic intent within 30 days prior to randomization.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ali Ataya, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Florida</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Christina M Eagan, DNP</last_name>
    <phone>352-273-8990</phone>
    <email>christina.eagan@medicine.ufl.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Rosie Kizza, RN</last_name>
    <phone>352-273-7225</phone>
    <email>rosie.kizza@medicine.ufl.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Florida, Division of Pulmonary and Critical Care Medicine</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christina M Eagan, DNP</last_name>
    </contact>
    <investigator>
      <last_name>Ali Ataya, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Divya C Patel, DO, MBA</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>January 4, 2019</study_first_submitted>
  <study_first_submitted_qc>January 22, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>May 17, 2023</last_update_submitted>
  <last_update_submitted_qc>May 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>right heart catheterization (RHC)</keyword>
  <keyword>pulmonary vascular resistance (PVR)</keyword>
  <keyword>mean pulmonary arterial pressure (mPAP)</keyword>
  <keyword>pulmonary hypertension (PH)</keyword>
  <keyword>Inhaled treprostinil</keyword>
  <keyword>Sarcoidosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Hypertension, Pulmonary</mesh_term>
    <mesh_term>Lung Diseases, Interstitial</mesh_term>
    <mesh_term>Hypertension</mesh_term>
    <mesh_term>Sarcoidosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Treprostinil</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03814317
org study id: OCR19684
secondary id: 20192572
nct id: NCT03814317
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study aims to evaluate the efficacy and safety of inhaled treprostinil in subjects with
      sarcoidosis-associated interstitial lung disease and pulmonary hypertension.
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.
allocation: N/A
intervention model: Single Group Assignment
intervention 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.
primary purpose: Treatment
masking: None (Open Label)
measure: PVR by Right heart catheterization (RHC)
time frame: Baseline, Week 16
description: Change in RHC parameter PVR (pulmonary vascular resistance )
measure: mPAP by Right heart catheterization (RHC)
time frame: Baseline, Week 16
description: Change in RHC parameter mPAP (mean pulmonary arterial pressure)
measure: Change in 6-Minute Walk Test (6MWT)
time frame: Baseline, Week 8, Week 16
description: change in walk test distance during the study
measure: Change in Cardiac MRI parameters
time frame: Baseline, Week 16
description: Change in Right ventricle ejection fraction, Right ventricular end diastolic ventricle index, right ventricular systolic index
measure: Change in Pulmonary Function Testing
time frame: Baseline, Week 16
description: Change in FEV1 abd FVC
measure: Change in Brain Natriuretic Peptide (BNP)
time frame: Baseline, Week 16
description: change in BNP level during the study
measure: Change in WHO Functional Class (WHO FC)
time frame: Baseline, Week 8, Week 16
description: change in WHO FC status during the study
arm group label: Study Group
arm group type: Experimental
description: 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.
intervention type: Drug
intervention name: Inhaled Treprostinil
description: 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.
arm group label: Study Group
other name: Tyvaso®
other name: pulmonary arterial hypertension (PAH) therapy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Ali Ataya, MD
role: Principal Investigator
affiliation: University of Florida
last name: Christina M Eagan, DNP
phone: 352-273-8990
email: christina.eagan@medicine.ufl.edu
last name: Rosie Kizza, RN
phone: 352-273-7225
email: rosie.kizza@medicine.ufl.edu
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Hypertension, Pulmonary
mesh term: Lung Diseases, Interstitial
mesh term: Hypertension
mesh term: Sarcoidosis
mesh term: Treprostinil
sharing ipd: No