Overview

Phase 2 Study to Assess Safety, Tolerability and Efficacy of Once Weekly SC Pemziviptadil (PB1046) in Subjects With Symptomatic PAH

Status:
Recruiting
Trial end date:
2021-12-31
Target enrollment:
0
Participant gender:
All
Summary
This is a multi-center, randomized, double-blind, controlled, Phase 2 study to assess the safety, tolerability, and efficacy of pemziviptadil (PB1046) at the optimally titrated dose after 16 weeks of treatment. Subjects will be randomized in a 2:1 ratio to one of two parallel dose groups: a) high-dose group where PB1046 will be up-titrated from a 0.2 mg/kg minimally effective starting dose to a target high dose level of at least 1.2 mg/kg or higher to a maximally tolerated dose (MTD), or b) a low-dose group that will start at 0.2 mg/kg and remain at this minimally effective dose (MED) level with sham up-titration. The total treatment period will be comprised of 2 phases: 1) an initial 10 week dose titration phase in which weekly doses of PB1046 will be titrated (or sham titrated) up to a target dose level of at least 1.2 mg/kg or higher to the MTD, and 2) a maintenance of treatment phase that begins when subjects reach week 11 and continues for 6 weeks during which no further up-titration should occur.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
PhaseBio Pharmaceuticals Inc.
Treatments:
Vasoactive Intestinal Peptide
VIP-ELP fusion molecule PB1046
Criteria
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;

- Two 6MWD test 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;

- Hemodynamic assessment of PAH 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;

- 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;

- Stable background medical regimen of up to 3 oral PAH therapies for at least 30 days
prior to Screening and having been on PAH therapy for at least 3 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 subcutaneous 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)

- 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.