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

Pulmonary Arterial Hypertension Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03795428
• Other study ID #: PB1046-PT-CL-0006
• Status: Terminated
• Phase: Phase 2
• Start date: April 10, 2019
• Est. completion date: January 11, 2022

Study information

• Verified date: February 2022
• Source: PhaseBio Pharmaceuticals Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: January 11, 2022
• Est. primary completion date: January 11, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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.

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• Pemziviptadil (PB1046) Injection
Once-weekly subcutaneous injection

Locations

Country	Name	City	State
United States	Emory University, The Emory Clinic	Atlanta	Georgia
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	The Lindner Center for Research and Education at The Christ Hospital	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of California San Diego	La Jolla	California
United States	University of Miami - Pulmonary Research Center	Miami	Florida
United States	NYU Langone Health	New York	New York
United States	INTEGRIS Baptist Medical Center	Oklahoma City	Oklahoma
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	UPMC Presbyterian	Pittsburgh	Pennsylvania
United States	University of Rochester Medical Center	Rochester	New York
United States	University of California - Davis	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
PhaseBio Pharmaceuticals Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in pulmonary artery pressure from baseline	PB1046-PT-CL-0005 subjects only as measured by CardioMEMS device	Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Other	Change in cardiac index from baseline	PB1046-PT-CL-0005 subjects only as measured by CardioMEMS device	Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Other	Change in total pulmonary resistance from baseline	PB1046-PT-CL-0005 subjects only as measured by CardioMEMS device	Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Primary	Incidence and Severity of Adverse Events		Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Primary	Incidence of Clinical Laboratory Abnormalities		Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Primary	Change in Diastolic Blood Pressure from baseline		Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Primary	Change in Systolic Blood Pressure from baseline		Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Primary	Change in Oral Body Temperature from baseline		Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Primary	Change in Respiratory Rate from baseline		Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Primary	Change in Heart Rate from baseline		Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Primary	12-Lead ECG - Incidence of clinically significant abnormal ECG findings as measured by 12 Lead ECG		Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Primary	Incidence of Immunogenicity	Incidence of positive immunogenicity results after receipt of study drug	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	Survival		Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Secondary	Change from baseline in 6MWD (6 minute walk distance test)	Measured in meters walked in 6 minutes.	Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Secondary	Change from baseline in NT-proBNP		Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Secondary	Change from baseline in NYHA/WHO Functional Class (FC)		Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Secondary	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.	Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Secondary	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)	Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Secondary	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	Duration of extension study - Starting the day of first dose and completing 28 days after last dose.
Secondary	Change in REVEAL Registry Risk Calculator Score	Risk scores range from 0 (Lowest risk) to 22 (Highest risk) in PAH subjects	Duration of extension study - Starting the day of first dose and completing 28 days after last dose.