<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/NCT03795428</url>
  </required_header>
  <id_info>
    <org_study_id>PB1046-PT-CL-0006</org_study_id>
    <nct_id>NCT03795428</nct_id>
  </id_info>
  <brief_title>Long-Term, Open Label Extension Study of Pemziviptadil (PB1046) in PAH Subjects Following Completion of Study PB1046-PT-CL-0004</brief_title>
  <acronym>VIP Extend</acronym>
  <official_title>A Long-Term, Open Label Extension Study of Pemziviptadil (PB1046) Subcutaneous Injections in Pulmonary Arterial Hypertension Subjects Following Completion of Study PB1046-PT-CL-0004</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PhaseBio Pharmaceuticals Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>PhaseBio Pharmaceuticals Inc.</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 is a multi-center, Phase 2 Long-Term, Open Label Extension (OLE) Study to assess the&#xD;
      safety and tolerability of pemziviptadil (PB1046) at an optimally titrated dose. This is a&#xD;
      Long-Term, Open label Extension (OLE) Study for subjects with (PAH), having participated in&#xD;
      double-blind Study PB1046-PT-CL-0004. The study will include adult subjects previously&#xD;
      diagnosed with symptomatic PAH, who are receiving background clinician-directed therapy for&#xD;
      PAH.&#xD;
&#xD;
      During this period, subjects will continue to be followed for safety and tolerability, as&#xD;
      well as for periodic efficacy, quality of life data and immunogenicity. The study will&#xD;
      continue per the schedule of events until such time when pemziviptadil (PB1046) is able to be&#xD;
      self-administered, becomes commercially available to the subjects in a particular country or&#xD;
      region, or the sponsor terminates the study due to lack of efficacy, safety or other reasons.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects entering this study will enter from the double-blind Study PB1046-PT-CL-0004. The&#xD;
      starting dose level of pemziviptadil (PB1046) for all subjects in this parent study was a&#xD;
      sub-therapeutic or minimally effective dose (MED) of 0.2 mg/kg, administered by SC injection.&#xD;
&#xD;
      Subjects were randomized into the MED) Group or a dose-titration group. In the dose-titration&#xD;
      group, individual subjects were titrated up to their maximum tolerated dose (MTD) in a&#xD;
      blinded fashion, with the objective of titrating subjects up to a dose of at least 1.2 mg/kg&#xD;
      or higher in the MTD Group, while subjects in the MED Group remained at the MED level of 0.2&#xD;
      mg/kg, and underwent &quot;sham dose-titration&quot; to maintain the blind.&#xD;
&#xD;
      Subjects entering the 0006 trial prior to implementation of this protocol amendment will&#xD;
      remain blinded until such time that open label dosing will not unblind the 0004 study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Terminated: Study drug resupply delayed (Covid-19)&#xD;
  </why_stopped>
  <start_date type="Actual">April 10, 2019</start_date>
  <completion_date type="Actual">January 11, 2022</completion_date>
  <primary_completion_date type="Actual">January 11, 2022</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>Sequential Assignment</intervention_model>
    <intervention_model_description>To protect the blind of the parent study (PB1046-PT-CL-0004), all subjects entering PB1046-PT-CL-0006 will commence dosing at Week 1 on 0.4 mg/kg and will be up-titrated in 0.2 mg/kg increments in an open label fashion for 9 weeks.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Subjects entering the 0006 trial prior to the implementation of this protocol amendment will remain blinded until such time that open label dosing will not unblind the 0004 study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence and Severity of Adverse Events</measure>
    <time_frame>Duration of extension study - Starting the day of first dose and completing 28 days after last dose.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Clinical Laboratory Abnormalities</measure>
    <time_frame>Duration of extension study - Starting the day of first dose and completing 28 days after last dose.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Diastolic Blood Pressure from baseline</measure>
    <time_frame>Duration of extension study - Starting the day of first dose and completing 28 days after last dose.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Systolic Blood Pressure from baseline</measure>
    <time_frame>Duration of extension study - Starting the day of first dose and completing 28 days after last dose.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Oral Body Temperature from baseline</measure>
    <time_frame>Duration of extension study - Starting the day of first dose and completing 28 days after last dose.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Respiratory Rate from baseline</measure>
    <time_frame>Duration of extension study - Starting the day of first dose and completing 28 days after last dose.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Heart Rate from baseline</measure>
    <time_frame>Duration of extension study - Starting the day of first dose and completing 28 days after last dose.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>12-Lead ECG - Incidence of clinically significant abnormal ECG findings as measured by 12 Lead ECG</measure>
    <time_frame>Duration of extension study - Starting the day of first dose and completing 28 days after last dose.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Immunogenicity</measure>
    <time_frame>Duration of extension study - Starting up to 30 days prior to first dose of study drug in original study (PB1046-PT-CL-0004/0005) and completing 28 days after last dose.</time_frame>
    <description>Incidence of positive immunogenicity results after receipt of study drug</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Survival</measure>
    <time_frame>Duration of extension study - Starting the day of first dose and completing 28 days after last dose.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in 6MWD (6 minute walk distance test)</measure>
    <time_frame>Duration of extension study - Starting the day of first dose and completing 28 days after last dose.</time_frame>
    <description>Measured in meters walked in 6 minutes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in NT-proBNP</measure>
    <time_frame>Duration of extension study - Starting the day of first dose and completing 28 days after last dose.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in NYHA/WHO Functional Class (FC)</measure>
    <time_frame>Duration of extension study - Starting the day of first dose and completing 28 days after last dose.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in emPHasis-10 (Health Related Quality of Life) score</measure>
    <time_frame>Duration of extension study - Starting the day of first dose and completing 28 days after last dose.</time_frame>
    <description>Scores, which assess breathlessness, fatigue, control and confidence, range from 0 to 50, higher scores indicate worse quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Borg Dyspnea Index (BDI)</measure>
    <time_frame>Duration of extension study - Starting the day of first dose and completing 28 days after last dose.</time_frame>
    <description>BDI scale as measured from 0 to 10 (0 being no breathlessness and 10 being maximal breathlessness)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Clinical Worsening</measure>
    <time_frame>Duration of extension study - Starting the day of first dose and completing 28 days after last dose.</time_frame>
    <description>As defined by any one of the following: 1. All cause mortality; 2. Hospitalization due to worsening PAH; 3. Initiation of parenteral prostacyclin; 4. Any three of the following: 15% decrease in 6MWD, Functional class III or IV symptoms, Addition of PAH therapy, Worsening right heart failure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in REVEAL Registry Risk Calculator Score</measure>
    <time_frame>Duration of extension study - Starting the day of first dose and completing 28 days after last dose.</time_frame>
    <description>Risk scores range from 0 (Lowest risk) to 22 (Highest risk) in PAH subjects</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in pulmonary artery pressure from baseline</measure>
    <time_frame>Duration of extension study - Starting the day of first dose and completing 28 days after last dose.</time_frame>
    <description>PB1046-PT-CL-0005 subjects only as measured by CardioMEMS device</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in cardiac index from baseline</measure>
    <time_frame>Duration of extension study - Starting the day of first dose and completing 28 days after last dose.</time_frame>
    <description>PB1046-PT-CL-0005 subjects only as measured by CardioMEMS device</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in total pulmonary resistance from baseline</measure>
    <time_frame>Duration of extension study - Starting the day of first dose and completing 28 days after last dose.</time_frame>
    <description>PB1046-PT-CL-0005 subjects only as measured by CardioMEMS device</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Pulmonary Arterial Hypertension</condition>
  <arm_group>
    <arm_group_label>Pemziviptadil (PB1046) Injection-OL Active Drug-Up-Titration to Stable Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pemziviptadil (PB1046) Injection: Regardless of dose assignment, all subjects will be up-titrated in 0.2 mg/kg weekly increments, beginning with 0.4 mg/kg at Week 1, to the target dose of 1.2 mg/kg or higher depending on safety and tolerability.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pemziviptadil (PB1046) Injection</intervention_name>
    <description>Once-weekly subcutaneous injection</description>
    <arm_group_label>Pemziviptadil (PB1046) Injection-OL Active Drug-Up-Titration to Stable Dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects must have completed Week 17 / End of Study of PB1046-PT-CL-0004;&#xD;
&#xD;
          -  Willing and able to sign a written Informed Consent (IC) prior to all study-related&#xD;
             procedures;&#xD;
&#xD;
          -  Agrees to use a medically acceptable method of contraception (both male and female&#xD;
             patients) throughout the entire study period and continuing for 30 days after their&#xD;
             last dose of study drug. if the possibility of conception exists. Medically acceptable&#xD;
             methods of contraception include the following: abstinence (not having sex), vasectomy&#xD;
             (with confirmed negative sperm counts), condoms and partner using vaginal spermicide&#xD;
             and/or cervical cap with spermicide or sponge; oral, implantable, or injectable&#xD;
             contraceptives (starting ˃2 months before dosing), diaphragm with vaginal spermicide,&#xD;
             intrauterine device, surgical sterilization (˃6 months after surgery). Female subjects&#xD;
             ˂45 years of age of non-childbearing potential are defined as being surgically sterile&#xD;
             by bilateral tubal ligation, bilateral oophorectomy, or hysterectomy. Female subjects&#xD;
             45to-60 years of age, inclusive, who are post-menopausal for at least 1 year, and have&#xD;
             a follicle-stimulating hormone (FSH) level confirmation indicating post-menopausal&#xD;
             status, will be considered to be of non-childbearing potential. Female subjects &gt; 60&#xD;
             years of age are considered post-menopausal and of non-childbearing potential;&#xD;
&#xD;
          -  Willing and able to understand and follow instructions, return to the study unit for&#xD;
             specified study visits; and, be able to participate in the study through the Stable&#xD;
             Dose Maintenance Period, at a minimum.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Concomitant medical disorder, condition, or history, that in the opinion of the&#xD;
             Investigator, would impair the subject's ability to participate in or complete the&#xD;
             requirements of the study;&#xD;
&#xD;
          -  Pregnant or lactating female subjects;&#xD;
&#xD;
          -  Significant liver dysfunction as measured by any one of the following during&#xD;
             participation in PB1046-PT-CL-0004. (If exclusionary laboratory results become&#xD;
             available after the subject has enrolled in PB1046-PT-CL-0006 they should be&#xD;
             discontinued. a. alanine aminotransferase (ALT) &gt; 3.0 times upper limit of normal&#xD;
             (ULN) or; b. aspartate aminotransferase (AST) &gt; 3.0 times ULN or; c. serum bilirubin ≥&#xD;
             1.6 mg/dL.&#xD;
&#xD;
          -  Recent history of substance abuse that, in the opinion of the Investigator, would&#xD;
             impair the subject's ability to participate in or complete the requirements of the&#xD;
             study;&#xD;
&#xD;
          -  In the opinion of the principal investigator (PI), any major surgical procedure within&#xD;
             90 days, or a planned surgical procedure during the study period; which would impact&#xD;
             participation in PB1046-PT-CL-0006.&#xD;
&#xD;
          -  Other new medical or psychiatric conditions which, in the opinion of the Investigator,&#xD;
             would place the subject at increased risk, would preclude obtaining voluntary consent,&#xD;
             or would confound the objectives of the study;&#xD;
&#xD;
          -  Known hypersensitivity to study drug or any of the excipients of the drug formulation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>79 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University of California San Diego</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California - Davis</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami - Pulmonary Research Center</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33125</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University, The Emory Clinic</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa Hospitals and Clinics</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Medical Center</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tufts Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU Langone Health</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Rochester Medical Center</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Lindner Center for Research and Education at The Christ Hospital</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>INTEGRIS Baptist Medical Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allegheny General Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Presbyterian</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>December 18, 2018</study_first_submitted>
  <study_first_submitted_qc>January 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 7, 2019</study_first_posted>
  <last_update_submitted>February 4, 2022</last_update_submitted>
  <last_update_submitted_qc>February 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Arterial Hypertension</mesh_term>
    <mesh_term>Familial Primary Pulmonary Hypertension</mesh_term>
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>VIP-ELP fusion molecule PB1046</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/NCT03795428
org study id: PB1046-PT-CL-0006
nct id: NCT03795428
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a multi-center, Phase 2 Long-Term, Open Label Extension (OLE) Study to assess the
      safety and tolerability of pemziviptadil (PB1046) at an optimally titrated dose. This is a
      Long-Term, Open label Extension (OLE) Study for subjects with (PAH), having participated in
      double-blind Study PB1046-PT-CL-0004. The study will include adult subjects previously
      diagnosed with symptomatic PAH, who are receiving background clinician-directed therapy for
      PAH.

      During this period, subjects will continue to be followed for safety and tolerability, as
      well as for periodic efficacy, quality of life data and immunogenicity. The study will
      continue per the schedule of events until such time when pemziviptadil (PB1046) is able to be
      self-administered, becomes commercially available to the subjects in a particular country or
      region, or the sponsor terminates the study due to lack of efficacy, safety or other reasons.
Subjects entering this study will enter from the double-blind Study PB1046-PT-CL-0004. The
      starting dose level of pemziviptadil (PB1046) for all subjects in this parent study was a
      sub-therapeutic or minimally effective dose (MED) of 0.2 mg/kg, administered by SC injection.

      Subjects were randomized into the MED) Group or a dose-titration group. In the dose-titration
      group, individual subjects were titrated up to their maximum tolerated dose (MTD) in a
      blinded fashion, with the objective of titrating subjects up to a dose of at least 1.2 mg/kg
      or higher in the MTD Group, while subjects in the MED Group remained at the MED level of 0.2
      mg/kg, and underwent "sham dose-titration" to maintain the blind.

      Subjects entering the 0006 trial prior to implementation of this protocol amendment will
      remain blinded until such time that open label dosing will not unblind the 0004 study.
allocation: N/A
intervention model: Sequential Assignment
intervention model description: To protect the blind of the parent study (PB1046-PT-CL-0004), all subjects entering PB1046-PT-CL-0006 will commence dosing at Week 1 on 0.4 mg/kg and will be up-titrated in 0.2 mg/kg increments in an open label fashion for 9 weeks.
primary purpose: Treatment
masking: None (Open Label)
masking description: Subjects entering the 0006 trial prior to the implementation of this protocol amendment will remain blinded until such time that open label dosing will not unblind the 0004 study.
measure: Incidence and Severity of Adverse Events
time frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
measure: Incidence of Clinical Laboratory Abnormalities
time frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
measure: Change in Diastolic Blood Pressure from baseline
time frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
measure: Change in Systolic Blood Pressure from baseline
time frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
measure: Change in Oral Body Temperature from baseline
time frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
measure: Change in Respiratory Rate from baseline
time frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
measure: Change in Heart Rate from baseline
time frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
measure: 12-Lead ECG - Incidence of clinically significant abnormal ECG findings as measured by 12 Lead ECG
time frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
measure: Incidence of Immunogenicity
time frame: Duration of extension study - Starting up to 30 days prior to first dose of study drug in original study (PB1046-PT-CL-0004/0005) and completing 28 days after last dose.
description: Incidence of positive immunogenicity results after receipt of study drug
measure: Survival
time frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
measure: Change from baseline in 6MWD (6 minute walk distance test)
time frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
description: Measured in meters walked in 6 minutes.
measure: Change from baseline in NT-proBNP
time frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
measure: Change from baseline in NYHA/WHO Functional Class (FC)
time frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
measure: Change from baseline in emPHasis-10 (Health Related Quality of Life) score
time frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
description: Scores, which assess breathlessness, fatigue, control and confidence, range from 0 to 50, higher scores indicate worse quality of life.
measure: Change from baseline in Borg Dyspnea Index (BDI)
time frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
description: BDI scale as measured from 0 to 10 (0 being no breathlessness and 10 being maximal breathlessness)
measure: Incidence of Clinical Worsening
time frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
description: As defined by any one of the following: 1. All cause mortality; 2. Hospitalization due to worsening PAH; 3. Initiation of parenteral prostacyclin; 4. Any three of the following: 15% decrease in 6MWD, Functional class III or IV symptoms, Addition of PAH therapy, Worsening right heart failure
measure: Change in REVEAL Registry Risk Calculator Score
time frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
description: Risk scores range from 0 (Lowest risk) to 22 (Highest risk) in PAH subjects
measure: Change in pulmonary artery pressure from baseline
time frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
description: PB1046-PT-CL-0005 subjects only as measured by CardioMEMS device
measure: Change in cardiac index from baseline
time frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
description: PB1046-PT-CL-0005 subjects only as measured by CardioMEMS device
measure: Change in total pulmonary resistance from baseline
time frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
description: PB1046-PT-CL-0005 subjects only as measured by CardioMEMS device
arm group label: Pemziviptadil (PB1046) Injection-OL Active Drug-Up-Titration to Stable Dose
arm group type: Experimental
description: Pemziviptadil (PB1046) Injection: Regardless of dose assignment, all subjects will be up-titrated in 0.2 mg/kg weekly increments, beginning with 0.4 mg/kg at Week 1, to the target dose of 1.2 mg/kg or higher depending on safety and tolerability.
intervention type: Drug
intervention name: Pemziviptadil (PB1046) Injection
description: Once-weekly subcutaneous injection
arm group label: Pemziviptadil (PB1046) Injection-OL Active Drug-Up-Titration to Stable Dose
criteria: 
gender: All
minimum age: 18 Years
maximum age: 79 Years
healthy volunteers: No
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country: United States
responsible party type: Sponsor
mesh term: Pulmonary Arterial Hypertension
mesh term: Familial Primary Pulmonary Hypertension
mesh term: Hypertension
mesh term: VIP-ELP fusion molecule PB1046
sharing ipd: No