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

NCT03795428 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: PB1046-PT-CL-0006
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 16

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.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (9)

• Incidence and Severity of Adverse Events

  Duration of extension study - Starting the day of first dose and completing 28 days after last dose.

• Incidence of Clinical Laboratory Abnormalities

  Duration of extension study - Starting the day of first dose and completing 28 days after last dose.

• Change in Diastolic Blood Pressure from baseline

  Duration of extension study - Starting the day of first dose and completing 28 days after last dose.

• Change in Systolic Blood Pressure from baseline

  Duration of extension study - Starting the day of first dose and completing 28 days after last dose.

• Change in Oral Body Temperature from baseline

  Duration of extension study - Starting the day of first dose and completing 28 days after last dose.

• Change in Respiratory Rate from baseline

  Duration of extension study - Starting the day of first dose and completing 28 days after last dose.

• Change in Heart Rate from baseline

  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

  Duration of extension study - Starting the day of first dose and completing 28 days after last dose.

• 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 Outcomes (8)

• Survival

  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)

  Duration of extension study - Starting the day of first dose and completing 28 days after last dose.

• Change from baseline in NT-proBNP

  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)

  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

  Duration of extension study - Starting the day of first dose and completing 28 days after last dose.

Other Outcomes (3)

• Change in pulmonary artery pressure from baseline

  Duration of extension study - Starting the day of first dose and completing 28 days after last dose.

• Change in cardiac index from baseline

  Duration of extension study - Starting the day of first dose and completing 28 days after last dose.

• Change in total pulmonary resistance from baseline

  Duration of extension study - Starting the day of first dose and completing 28 days after last dose.

Study Arms (1)

Pemziviptadil (PB1046) Injection-OL Active Drug-Up-Titration to Stable Dose

EXPERIMENTAL

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

Interventions

Pemziviptadil (PB1046) Injection DRUG

Once-weekly subcutaneous injection

Pemziviptadil (PB1046) Injection-OL Active Drug-Up-Titration to Stable Dose

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• PhaseBio Pharmaceuticals Inc.: lead

Study Sites (16)

University of California San Diego

La Jolla, California, 92037, United States

Location

University of California - Davis

Sacramento, California, 95817, United States

Location

University of Miami - Pulmonary Research Center

Miami, Florida, 33125, United States

Location

Emory University, The Emory Clinic

Atlanta, Georgia, 30322, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

The Lindner Center for Research and Education at The Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

INTEGRIS Baptist Medical Center

Oklahoma City, Oklahoma, 73112, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

UPMC Presbyterian

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

VIP-ELP fusion molecule PB1046; Injections

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 18, 2018
• First Posted: January 7, 2019
• Study Start: April 10, 2019
• Primary Completion: January 11, 2022
• Study Completion: January 11, 2022
• Last Updated: February 22, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)