Long-Term, Open Label Extension Study of Pemziviptadil (PB1046) in PAH Subjects Following Completion of Study PB1046-PT-CL-0004 (VIP Extend)
Primary Purpose
Pulmonary Arterial Hypertension
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pemziviptadil (PB1046) Injection
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Arterial Hypertension
Eligibility 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.
Sites / Locations
- University of California San Diego
- University of California - Davis
- University of Miami - Pulmonary Research Center
- Emory University, The Emory Clinic
- University of Iowa Hospitals and Clinics
- University of Kansas Medical Center
- Tufts Medical Center
- Brigham and Women's Hospital
- NYU Langone Health
- University of Rochester Medical Center
- The Lindner Center for Research and Education at The Christ Hospital
- University of Cincinnati
- INTEGRIS Baptist Medical Center
- Allegheny General Hospital
- UPMC Presbyterian
- University of Texas Southwestern Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pemziviptadil (PB1046) Injection-OL Active Drug-Up-Titration to Stable Dose
Arm 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.
Outcomes
Primary Outcome Measures
Incidence and Severity of Adverse Events
Incidence of Clinical Laboratory Abnormalities
Change in Diastolic Blood Pressure from baseline
Change in Systolic Blood Pressure from baseline
Change in Oral Body Temperature from baseline
Change in Respiratory Rate from baseline
Change in Heart Rate from baseline
12-Lead ECG - Incidence of clinically significant abnormal ECG findings as measured by 12 Lead ECG
Incidence of Immunogenicity
Incidence of positive immunogenicity results after receipt of study drug
Secondary Outcome Measures
Survival
Change from baseline in 6MWD (6 minute walk distance test)
Measured in meters walked in 6 minutes.
Change from baseline in NT-proBNP
Change from baseline in NYHA/WHO Functional Class (FC)
Change from baseline in emPHasis-10 (Health Related Quality of Life) score
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)
BDI scale as measured from 0 to 10 (0 being no breathlessness and 10 being maximal breathlessness)
Incidence of Clinical Worsening
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
Risk scores range from 0 (Lowest risk) to 22 (Highest risk) in PAH subjects
Full Information
NCT ID
NCT03795428
First Posted
December 18, 2018
Last Updated
February 4, 2022
Sponsor
PhaseBio Pharmaceuticals Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03795428
Brief Title
Long-Term, Open Label Extension Study of Pemziviptadil (PB1046) in PAH Subjects Following Completion of Study PB1046-PT-CL-0004
Acronym
VIP Extend
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Terminated
Why Stopped
Terminated: Study drug resupply delayed (Covid-19)
Study Start Date
April 10, 2019 (Actual)
Primary Completion Date
January 11, 2022 (Actual)
Study Completion Date
January 11, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PhaseBio Pharmaceuticals Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
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.
Allocation
N/A
Enrollment
25 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pemziviptadil (PB1046) Injection-OL Active Drug-Up-Titration to Stable Dose
Arm Type
Experimental
Arm 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(s)
Pemziviptadil (PB1046) Injection
Intervention Description
Once-weekly subcutaneous injection
Primary Outcome Measure Information:
Title
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.
Title
Incidence of Clinical Laboratory Abnormalities
Time Frame
Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Title
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.
Title
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.
Title
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.
Title
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.
Title
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.
Title
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.
Title
Incidence of Immunogenicity
Description
Incidence of positive immunogenicity results after receipt of study drug
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.
Secondary Outcome Measure Information:
Title
Survival
Time Frame
Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Title
Change from baseline in 6MWD (6 minute walk distance test)
Description
Measured in meters walked in 6 minutes.
Time Frame
Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Title
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.
Title
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.
Title
Change from baseline in emPHasis-10 (Health Related Quality of Life) score
Description
Scores, which assess breathlessness, fatigue, control and confidence, range from 0 to 50, higher scores indicate worse quality of life.
Time Frame
Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Title
Change from baseline in Borg Dyspnea Index (BDI)
Description
BDI scale as measured from 0 to 10 (0 being no breathlessness and 10 being maximal breathlessness)
Time Frame
Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Title
Incidence of Clinical Worsening
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
Time Frame
Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Title
Change in REVEAL Registry Risk Calculator Score
Description
Risk scores range from 0 (Lowest risk) to 22 (Highest risk) in PAH subjects
Time Frame
Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Other Pre-specified Outcome Measures:
Title
Change in pulmonary artery pressure from baseline
Description
PB1046-PT-CL-0005 subjects only as measured by CardioMEMS device
Time Frame
Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Title
Change in cardiac index from baseline
Description
PB1046-PT-CL-0005 subjects only as measured by CardioMEMS device
Time Frame
Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Title
Change in total pulmonary resistance from baseline
Description
PB1046-PT-CL-0005 subjects only as measured by CardioMEMS device
Time Frame
Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
University of California San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
University of California - Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of Miami - Pulmonary Research Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33125
Country
United States
Facility Name
Emory University, The Emory Clinic
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
The Lindner Center for Research and Education at The Christ Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
INTEGRIS Baptist Medical Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
Allegheny General Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15212
Country
United States
Facility Name
UPMC Presbyterian
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Long-Term, Open Label Extension Study of Pemziviptadil (PB1046) in PAH Subjects Following Completion of Study PB1046-PT-CL-0004
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