A Study of the Safety, Tolerability and Effectiveness of the Experimental Medicine PB1046 for Pulmonary Arterial Hypertension

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"Volunteer for research at UC Davis and contribute to discoveries that may improve health care for you, your family, and your community!"
Age: 18 to 79 years old
Gender:
Any
Healthy Volunteers: No
Keywords: Pulmonary Arterial Hypertension
Type: Drug study, Phase 2
Target:
7 Participants
Investigator:
Description
This is a research study involving an investigational drug called PB1046. "Investigational" means that the drug is not yet approved by the FDA.

The study drug contains an active ingredient similar to a protein called vasoactive intestinal peptide (VIP). The VIP protein is normally found in the body. The change made to the natural protein helps to protect the protein from breaking down too quickly. Scientific sources state that the amount of VIP may be lower in people with pulmonary arterial hypertension (PAH).

The purpose of this study is to see how well participants with PAH tolerate the study drug. We will also study how much of the study drug is absorbed into the bloodstream and how long it stays in the blood stream (called pharmacokinetics). The study will also see whether your body makes antibodies against the study drug.

Antibodies are proteins produced by the body's immune system. They are usually found in the blood that help protect our bodies from harm by finding and destroying invaders, like bacteria and viruses. They can also cause harm when they find other proteins that are not normally in the body like the study drug. These antibodies can make the study drug, or the natural VIP found in our bodies not work as well or not at all. In addition, the study will look at the effect of the study drug on special markers in the blood that are related to PAH.
This study requires

The study team will make sure you qualify to take part in the study. Qualified participants will receive detailed information about the study. This may include a list of study-related tests and procedures.

Who can participate

Inclusion criteria:

  • 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;
  • Willing and able to sign a written informed consent prior to all study-related procedures;
  • 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);
  • Two 6MWD test results > 50 m and < 525 m prior to dosing with results +/- 10% of each other. Note: Up to four tests may be conducted between Screening and Baseline for eligibility purposes (no more than two 6MWD tests may be performed on the same day, and must be completed at least two hours apart);
  • Hemodynamic assessment of PAH by right heart catheterization (RHC) demonstrating elevated mPAP and PVR as indicated below during the Screening Period: a. mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg; and, b. pulmonary vascular resistance (PVR) ≥ 400 dyne•sec/cm5; and, c. pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) of ≤ 12 mmHg if PVR ≥ 400 and < 500 dynes•sec/cm5; or PCWP/LVEDP ≤ 15 mmHg if PVR ≥ 500 dynes•sec/cm5;
  • Body mass index ≥ 18 kg/m2 and ≤ 40 kg/m2 at screening;
  • 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) ≥ 55% of predicted normal, b. FEV1: FVC (forced vital capacity) ratio ≥ 0.60;
  • Male subjects and female subjects of childbearing potential willing and able to practice effective contraception during the study and continuing contraception for 30 days after their last dose of study drug. Female subjects of non-childbearing potential are defined as being surgically sterile by bilateral tubal ligation, bilateral oophorectomy, or hysterectomy. A female subject 45 to 60 year of age, inclusive who is post-menopausal for at least 1 year and has a follicle-stimulating hormone level confirmation indicating post-menopausal status will be considered of non-childbearing potential. Female subjects >60 years of age are considered post-menopausal and of non-childbearing potential;
  • Stable background medical regimen of up to 2 oral PAH therapies for at least 30 days prior to Screening and having been on PAH therapy for at least 4 months;
  • If a subject has historical diagnosis (prior to screening visit) of being positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV), must be clinically stable and if on therapy, must be on stable therapy for HIV or HCV for at least 3 months; Willing and able to understand and follow instructions; return to the study unit for specified study visits; and able to participate in the study for the entire period.

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;
  • Concomitant medical disorder that is expected to limit the subject's life-expectancy to ≤ 1 year;
  • Pregnant or lactating female subjects;
  • First positive result from serology testing at visit 1 (screening labs) for HIV, HBsAg, or HCV prior to randomization;
  • 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;
  • Use of chronic prostanoid/prostacyclin therapy for PAH within 30 days prior to screening, including prostacyclin receptor agonists;
  • 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;
  • Sustained systolic blood pressure (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;
  • 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;
  • Clinically significant renal dysfunction at the Screening Visit as measured by the estimated glomerular filtration rate (eGFR) of < 40 mL/min/1.73m2 as calculated by the MDRD equation: eGFR = 186 x (Creat / 88.4)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if black)
  • Significant liver dysfunction as measured by any one of the following at screening: 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;
  • 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;
  • Any major surgical procedure within 90 days prior to screening or planned surgical procedure during the study period;
  • Any in-patient hospitalization (defined as greater than 23 hours) within 30 days of subject screening;
  • Enrollment within the past 3 months prior to screening or plans to enroll during the study into a cardiopulmonary rehabilitation program;
  • 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;
  • Known hypersensitivity to study drug or any of the excipients of the drug formulation;
  • More than two 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.
Benefits and risks of participating
BENEFITS:

We cannot promise any benefits to you as a result of taking part in this research study.


RISKS:

The study doctor will discuss the risks associated with taking part in this research study.
Compensation
If you agree to take part in this research study, we will compensate you for each completed study visit as listed below.

Visit 1: $100
Visit 2: $300
Visits 3 - 11: $100 each
Visit 12: $300
Visits 13 - 17d: $100 each
Visit 18: $300
Visits 19 - 20: $100 each
Unscheduled Visit: $50 each
Additional Immunogenicity sampling: $50.00 each
Resources
Schedule
Study duration and period
You will be in this research study for at least 25 weeks and will include about 20 office and/or home visits.
Recruitment period
From Nov. 5, 2018
Location
UC Davis Medical Center
2315 Stockton Boulevard
Sacramento, CA 95817
Contact
Macey Sockolov
Research Topic
Conditions:
  • Pulmonary Arterial Hypertension