Phase 2 Study to Assess Safety, Tolerability and Efficacy of Once Weekly Subcutaneous Injections of PB1046 (study drug) in Subjects With Symptomatic Pulmonary Arterial Hypertensio
- Conditions
- Symptomatic Pulmonary Arterial HypertensionMedDRA version: 21.1Level: PTClassification code 10064911Term: Pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2019-001598-10-ES
- Lead Sponsor
- PhaseBio Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 63
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, > or =18 and < or = 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 < 550 m prior to randomization with results +/- 10% of each other. Note: Up to four tests may be conducted between Screening and Randomization for eligibility purposes (no more than two 6MWT may be performed on the same day, and must be completed at least two hours apart)
5. Hemodynamic assessment of PAH by right heart catheterization (RHC) demonstrating elevated mPAP and PVR as indicated below during the Screening Period
a. mPAP of > or = 25 mmHg; and
b. PVR > or = 400 dyne•sec/cm5; and
c. PCWP or left ventricular end diastolic pressure (LVEDP) of < or = 12 mmHg if PVR > or = 400 and < 500 dynes•sec/cm5; or PCWP/LVEDP < or = 15 mmHg if PVR > or = 500 dynes•sec/cm5
6. Body mass index (BMI) > or = 18 kg/m2 and < or = 40 kg/m2 at screening
7. Meet the following criteria determined by pulmonary function tests completed no more than 24 weeks prior to screening
a. Forced expiratory volume in one second (FEV1) > or = 55% of predicted normal
b. FEV1: FVC (forced vital capacity) ratio > or = 0.60
8. 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 subject 45 to 60 years of age, inclusive, who is 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
9. Stable background medical regimen of up to 3 PAH disease-specific therapies for at least 3 months comprised of any combination of oral and/or inhaled or IV therapy and at stable doses for at least 30 days prior to Screening
10. If a subject has historical diagnosis (prior to sc
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 < or = 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 < 50%, or left ventricular regional wall motion abnormality suggestive of active coronary artery disease on documented 2D-echocardiography occurring within 12 months of Screening
8. Sustained SBP < 95 mmHg and/or diastolic blood pressure (DBP) < 50 mmHg (confirmed by a duplicate seated reading) on at least 3 consecutive readings (self-monitored or office) at screening and prior to dosing, or overt symptomatic hypotension
9. Sustained resting heart rate >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 < 30 mL/min/1.73m2 as calculated by the IDMS-Traceable MDRD equation: eGFR = (mL/min/1.73 m2) = 175 x (serum creatinine in mg/dL) – 1.154 x (Age) – 0.203 x (0.742 if female) x (1.212 if African American) (conventional units)
11. Significant liver dysfunction as measured by any one of the following at screening:
a. alanine aminotransferase (ALT) >3.0 times ULN or
b. aspartate aminotransferase (AST) >3.0 times ULN or
c. serum bilirubin > or = 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method