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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.

Tracking Information
First Submitted Date  ICMJE December 18, 2018
First Posted Date  ICMJE January 7, 2019
Last Update Posted Date October 6, 2020
Actual Study Start Date  ICMJE April 10, 2019
Estimated Primary Completion Date January 15, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 4, 2019)
  • 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. ]
  • Incidence of Clinical Laboratory Abnormalities [ Time Frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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. ]
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 4, 2019)
  • Survival [ Time Frame: Duration of extension study - Starting the day of first dose and completing 28 days after last dose. ]
  • 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.
  • 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. ]
  • 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. ]
  • 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.
  • 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)
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: January 4, 2019)
  • 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
  • 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
  • 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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Long-Term, Open Label Extension Study of Pemziviptadil (PB1046) in PAH Subjects Following Completion of Study PB1046-PT-CL-0004
Official Title  ICMJE 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
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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.
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
Condition  ICMJE Pulmonary Arterial Hypertension
Intervention  ICMJE Drug: Pemziviptadil (PB1046) Injection
Once-weekly subcutaneous injection
Study Arms  ICMJE 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.
Intervention: Drug: Pemziviptadil (PB1046) Injection
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 17, 2019)
63
Original Estimated Enrollment  ICMJE
 (submitted: January 4, 2019)
64
Estimated Study Completion Date  ICMJE February 15, 2024
Estimated Primary Completion Date January 15, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 79 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03795428
Other Study ID Numbers  ICMJE PB1046-PT-CL-0006
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party PhaseBio Pharmaceuticals Inc.
Study Sponsor  ICMJE PhaseBio Pharmaceuticals Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account PhaseBio Pharmaceuticals Inc.
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP