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Long-Term, Open Label Extension Study of Pemziviptadil (PB1046) in PAH Subjects Following Completion of Study PB1046-PT-CL-0004 (VIP Extend)

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ClinicalTrials.gov Identifier: NCT03795428
Recruitment Status : Recruiting
First Posted : January 7, 2019
Last Update Posted : October 6, 2020
Sponsor:
Information provided by (Responsible Party):
PhaseBio Pharmaceuticals Inc.

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Pulmonary Arterial Hypertension Drug: Pemziviptadil (PB1046) Injection Phase 2

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 63 participants
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.
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.
Primary Purpose: Treatment
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
Actual Study Start Date : April 10, 2019
Estimated Primary Completion Date : January 15, 2024
Estimated Study Completion Date : February 15, 2024


Arm Intervention/treatment
Experimental: Pemziviptadil (PB1046) Injection-OL Active Drug-Up-Titration to Stable Dose
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.
Drug: Pemziviptadil (PB1046) Injection
Once-weekly subcutaneous injection




Primary Outcome Measures :
  1. 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. ]
  2. Incidence of Clinical Laboratory Abnormalities [ Time Frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose. ]
  3. 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. ]
  4. 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. ]
  5. 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. ]
  6. 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. ]
  7. 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. ]
  8. 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. ]
  9. 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. ]
    Incidence of positive immunogenicity results after receipt of study drug


Secondary Outcome Measures :
  1. Survival [ Time Frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose. ]
  2. 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. ]
    Measured in meters walked in 6 minutes.

  3. 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. ]
  4. 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. ]
  5. 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. ]
    Scores, which assess breathlessness, fatigue, control and confidence, range from 0 to 50, higher scores indicate worse quality of life.

  6. 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. ]
    BDI scale as measured from 0 to 10 (0 being no breathlessness and 10 being maximal breathlessness)

  7. Incidence of Clinical Worsening [ Time Frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose. ]
    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

  8. 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. ]
    Risk scores range from 0 (Lowest risk) to 22 (Highest risk) in PAH subjects


Other Outcome Measures:
  1. 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. ]
    PB1046-PT-CL-0005 subjects only as measured by CardioMEMS device

  2. 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. ]
    PB1046-PT-CL-0005 subjects only as measured by CardioMEMS device

  3. 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. ]
    PB1046-PT-CL-0005 subjects only as measured by CardioMEMS device



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have completed Week 17 / End of Study of PB1046-PT-CL-0004;
  • Willing and able to sign a written Informed Consent (IC) prior to all study-related procedures;
  • Agrees to use a medically acceptable method of contraception (both male and female patients) throughout the entire study period and continuing for 30 days after their last dose of study drug. if the possibility of conception exists. Medically acceptable methods of contraception include the following: abstinence (not having sex), vasectomy (with confirmed negative sperm counts), condoms and partner using vaginal spermicide and/or cervical cap with spermicide or sponge; oral, implantable, or injectable contraceptives (starting ˃2 months before dosing), diaphragm with vaginal spermicide, intrauterine device, surgical sterilization (˃6 months after surgery). Female subjects ˂45 years of age of non-childbearing potential are defined as being surgically sterile by bilateral tubal ligation, bilateral oophorectomy, or hysterectomy. Female subjects 45to-60 years of age, inclusive, who are post-menopausal for at least 1 year, and have a follicle-stimulating hormone (FSH) level confirmation indicating post-menopausal status, will be considered to be of non-childbearing potential. Female subjects > 60 years of age are considered post-menopausal and of non-childbearing potential;
  • Willing and able to understand and follow instructions, return to the study unit for specified study visits; and, be able to participate in the study through the Stable Dose Maintenance Period, at a minimum.

Exclusion Criteria:

  • Concomitant medical disorder, condition, or history, that in the opinion of the Investigator, would impair the subject's ability to participate in or complete the requirements of the study;
  • Pregnant or lactating female subjects;
  • Significant liver dysfunction as measured by any one of the following during participation in PB1046-PT-CL-0004. (If exclusionary laboratory results become available after the subject has enrolled in PB1046-PT-CL-0006 they should be discontinued. a. alanine aminotransferase (ALT) > 3.0 times upper limit of normal (ULN) or; b. aspartate aminotransferase (AST) > 3.0 times ULN or; c. serum bilirubin ≥ 1.6 mg/dL.
  • Recent history of substance abuse that, in the opinion of the Investigator, would impair the subject's ability to participate in or complete the requirements of the study;
  • In the opinion of the principal investigator (PI), any major surgical procedure within 90 days, or a planned surgical procedure during the study period; which would impact participation in PB1046-PT-CL-0006.
  • Other new medical or psychiatric conditions which, in the opinion of the Investigator, would place the subject at increased risk, would preclude obtaining voluntary consent, or would confound the objectives of the study;
  • Known hypersensitivity to study drug or any of the excipients of the drug formulation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03795428


Locations
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United States, California
University of California San Diego Recruiting
La Jolla, California, United States, 92037
Contact: Paola M Ceren    858-657-7135    pmm001@health.ucsd.edu   
Principal Investigator: David S Poch, MD         
University of California - Davis Recruiting
Sacramento, California, United States, 95817
Contact: Nikhil Jaha    916-734-1554    nkjaha@ucdavis.edu   
Principal Investigator: Roblee Allen, MD         
United States, Georgia
Emory University, The Emory Clinic Recruiting
Atlanta, Georgia, United States, 30322
Contact: Jane Gillespie    404-712-8204    jane.gillespie@emory.edu   
Principal Investigator: Micah Fisher, MD         
United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52242
Contact: Traci Parks, RN, BSN    319-353-5236    traci-parks@uiowa.edu   
Principal Investigator: Linda M Cadaret, MD         
United States, Kansas
University of Kansas Medical Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Luigi Boccardi    913-588-4022    lboccardi@kumc.edu   
Principal Investigator: Leslie A Spikes, MD         
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Olivia Vayer    617-525-9731    Ovayer@bwh.harvard.edu   
Contact: Diana Acuna    617-732-4954    Dacuna@bwh.harvard.edu   
Principal Investigator: Aaron Waxman, MD, PhD         
United States, New York
University of Rochester Medical Center Recruiting
Rochester, New York, United States, 14642
Contact: Andrew Mintz, RN    585-486-0869    urmc_pahresearch@urmc.rochester.edu   
Principal Investigator: R. James White, MD         
United States, Ohio
The Lindner Center for Research and Education at The Christ Hospital Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Ellen Anderson    513-585-1777    ellen.anderson@thechristhospital.com   
Principal Investigator: Peter Engel, MD         
United States, Pennsylvania
Allegheny General Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15212
Contact: Amresh Raina, MD    412-737-4760    Amresh.Raina@ahn.org   
Principal Investigator: Amresh Raina, MD         
UPMC Presbyterian Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Kristin Shoemaker    412-692-2769    shoeka@upmc.edu   
Principal Investigator: Marc Simon, M.D.         
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Sonja Bartolome, MD    214-645-6493    sonja.bartolome@utsouthwestern.edu   
Principal Investigator: Sonja Bartolome, MD         
Sponsors and Collaborators
PhaseBio Pharmaceuticals Inc.
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Responsible Party: PhaseBio Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT03795428    
Other Study ID Numbers: PB1046-PT-CL-0006
First Posted: January 7, 2019    Key Record Dates
Last Update Posted: October 6, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Familial Primary Pulmonary Hypertension
Hypertension
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases