Symptomatic Pulmonary Arterial Hypertension MedDRA version: 21.1 Level: PT Classification code 10064911 Term: Pulmonary arterial hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: Vasomera (PB1046) Injection
Product Code: PB1046
Pharmaceutical Form: Solution for injection
INN or Proposed INN: not available
CAS Number: N/A
Current Sponsor code: PB1046
Other descrip
Sponsors
PhaseBio Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects will be eligible for inclusion in the study if they meet all the following criteria at screening and up to the time of first dose as indicated: 1. Male and female subjects with PAH, =18 and = 79 years of age, who are symptomatic and have reduced exercise capacity due primarily to their PAH diagnosis and have been assessed by a qualified individual (i.e. physician, physician assistant, nurse practitioner) to be in NYHA/WHO functional class II or III 2. Willing and able to sign a written informed consent prior to all study-related procedures 3. Subjects with PAH belonging to one of the following subgroups of the NICE Clinical Classification of Pulmonary Hypertension Group 1: a. Idiopathic b. Heritable c. Drug or toxin-induced d. Associated with connective tissue disease, HIV infection, portal hypertension, congenital heart disease (pulmonary-to-systemic shunt, e.g., atrial septal defect (ASD) or patent ductus arteriosus (PDA), at least 1 year after surgical repair) 4. Two 6MWT results > 50 m and 60 years of age are considered post-menopausal and of non-childbearing potential 9. S
Exclusion criteria
Exclusion criteria: Subjects will be excluded from the study if they meet any of the following criteria: 1. 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 2. Concomitant medical disorder that is expected to limit the subject’s life-expectancy to = 1 year 3. Pregnant or lactating female subjects 4. First positive result from serology testing at Visit 1 (screening labs) for HIV, HBsAg, or HCV prior to randomization 5. Participation in another investigational drug study within 30 days prior to screening or participating in a non-medication study which, in the opinion of the Investigator, would interfere with the study compliance or outcome assessments 6. Use of subcutaneous prostanoid/prostacyclin therapy for PAH within 30 days prior to the screening visit 7. More than mild mitral or aortic valve disease, left ventricular ejection fraction 110 beats per minute (BPM) (confirmed by duplicate assessments of office vital signs or consecutive ECG assessments) on at least 3 consecutive readings at screening and prior to dosing 10. Clinically significant renal dysfunction based on Screening labs as measured by the estimated glomerular filtration rate (eGFR) of 3.0 times ULN or b. aspartate aminotransferase (AST) >3.0 times ULN or c. serum bilirubin = 1.6 mg/dL 12. Known history of substance abuse within the past 1 year that in the opinion of the Investigator would impair the subject’s ability to participate in or complete the requirements of the study 13. Any major surgical procedure within 90 days prior to screening or planned surgical procedure during the study period 14. Any in-patient hospitalization (defined as greater than 23 hours) within 30 days of subject screening 15. Enrollment within the past 3 months prior to screening or plans to enroll during the study into a cardiopulmonary rehabilitation program 16. Other medical or psychiatric condition which, in the opinion of the Investigator, would place the subject at increased risk or would preclude obtaining voluntary consent or would confound the objectives of study 17. Known hypersensitivity to study drug or any of the excipients of the drug formulation; 18. Three or more of the following: a. BMI >35 b. Current atrial fibrillation c. Current Diabetes Mellitus d. Current Hypertension e. History of clinically significant coronary artery disease in prior 3 years
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Assess the safety, tolerability, and effect on pulmonary vascular resistance (PVR) of dose titrated levels of PB1046 administered subcutaneously once-weekly for 16 weeks in subjects with symptomatic pulmonary arterial hypertension (PAH);Secondary Objective: • To investigate the effect of PB1046 on exercise capacity following treatment in PAH subjects • To investigate the effect of PB1046 on change in N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP) • To investigate the effect of PB1046 on cardiopulmonary hemodynamics • To evaluate the multi-dose pharmacokinetic profile of individually dose-titrated PB1046 administered once-weekly for 16 weeks • To evaluate the immunogenicity profile of PB1046 PAH subjects;Primary end point(s): Primary Efficacy Endpoint: Change from Baseline to end of assessment in Pulmonary Vascular Resistance (PVR);Timepoint(s) of evaluation of this end point: Right Heart Catherization (RHC) performed between Screening and Baseline and between Visits 17 (End of Treatment) and 18, preferably 48 to 72 hours after the last dose. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints: 1. Change from Baseline to end of assessment in: • Six Minute Walk Test (6MWT) • NT-proBNP • Cardiac index (CI), mean pulmonary artery pressure (mPAP), mean right atrial pressure (mRAP), pulmonary capillary wedge pressure (PCWP), mixed venous oxygen saturation (SvO2), including pulmonary artery compliance 2. Safety Endpoints • Incidence and severity of AEs and their relationship to study drug • Vital signs, laboratory parameters, electrocardiograms (ECGs) and their relationship to PB1046 • Immunogenicity 3. Pharmacokinetic Endpoints: • Plasma PB1046 concentration at each time point and PK parameters;Timepoint(s) of evaluation of this end point: 1. From Baseline (V2) to end of assessment (V18) 2. From Baseline (V2) to the day of enrollment in the open-label extension (OLE) study PB1046-PT-CL-0006 (V18) or 2. For those not opting to continue into the OLE, safety endpoints will continue to be collected for 28 days after the final dose of PB1046 (V18). Moreover, approximately 56 days after the final dose (V18) a blood sample will be also drawn for immunogenicity testing. If anti-drug antibodies are still present at 56 days post last dose, then subjects will be followed further until resolution of the antibody status. 3. From Baseline to end of assessment | — |
Countries
Austria, Belgium, Bulgaria, Czech Republic, Germany, Greece, Hungary, Italy, Poland, Romania, Serbia, Spain, United States
Contacts
Public ContactPB1046 Clinical Project Manager
PhaseBio Pharmaceuticals, Inc.
Outcome results
None listed