Study to Assess the Safety, Tolerability and PK/PD After 4 Weekly SC Injections of PB1046 in Subjects With Stable HFrEF
Condition: Heart Failure
MeSH terms: Heart Failure
Intervention: PB1046 Injection; Placebo Injection
Intervention description: Four weekly subcutaneous injections of PB1046.; Four weekly subcutaneous injections of placebo.
Intervention MeSH terms: VIP-ELP fusion molecule PB1046
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study will be a sequential multiple-dose escalation study that will enroll (randomize
      and dose) approximately 28 subjects in four cohorts consisting of 3 active and 1 placebo in
      Cohort 1 and 6 active and 2 placebo in subsequent cohorts. Randomized subjects will receive a
      fixed weekly dose of study drug or placebo for a 4 week dosing period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Willing and able to sign a written informed consent and follow all study-related
             procedures,

          -  Male subjects and female subjects of reproductive or childbearing potential must
             practice effective contraception during the study and be willing and able to continue
             contraception for 30 days after their last dose of study drug,

          -  Body mass index ≥ 18 kg/m2 and ≤ 45 kg/m2,

          -  Receipt of stable pharmacological therapy(ies) for heart failure for a minimum of 1
             month prior to screening and between screening and randomization and are in stable
             clinical condition,

          -  NYHA Class II or III heart failure diagnosis (ischemic or non-ischemic confirmed by
             medical history) at least 6 months prior to screening,

          -  Stable HF defined as no hospitalizations for cardiac related issues within the
             previous 3 months prior to the screening visit or between screening and randomization,

          -  A screening or historical Left Ventricular Ejection Fraction ≤ 40% by centralized
             reading of 2-D echocardiography,

          -  Screening hemoglobin ≥ 9.0 g/dL secondary to the volume of blood to be collected
             during the study period,

          -  Willing and able to return to the study unit for specified study visits, and be able
             to self-monitor blood pressure while at home,

          -  Live and work in an area with reliable cellular services (e.g., Sprint®) for real time
             transmission of telemetry data to the core laboratory.

        Exclusion Criteria:

          -  Have previously received PB1046 or have a known allergy to the study drug or any of
             its components,

          -  Participating in any other study and have received any other investigational
             medication or device within 30 days prior to screening or are taking part in a
             non-medication study which, in the opinion of the Investigator, would interfere with
             study compliance or outcome assessments,

          -  Diagnosed with acute coronary syndrome (ACS) or an acute myocardial infarction (MI)
             within 3 months of screening,

          -  Canadian Cardiovascular Society (CCS) Class III or IV angina necessitating frequent
             use of as needed short acting nitroglycerin,

          -  Cardiac surgery or valvuloplasty within 3 months prior to screening,

          -  Cerebrovascular accident or transient ischemic attack within 3 months prior to
             screening,

          -  Sustained systolic blood pressure (SBP) < 110 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) prior to randomization or overt symptomatic
             hypotension,

          -  Sustained resting heart rate >100 beats per minute (BPM) at screening (V1) or prior to
             randomization,

          -  History or evidence of clinically significant arrhythmias (uncontrolled by drug
             therapy or use of an implantable defibrillator), long QT syndrome or evidence of QT
             prolongation demonstrating QTcF > 460 ms prior to randomization (Subjects with QTcF
             >460 ms due to electronic pacing by an implanted pacemaker/ICD device may be
             enrolled),

          -  Clinically significant renal dysfunction as measured by the estimated glomerular
             filtration rate (eGFR) of < 40 mL/min/1.73m2 as calculated by the CKD-EPI
             creatinine-cystatin C equation at screening, or a clinically significant change in
             renal function between screening and baseline,

          -  Clinically significant liver dysfunction as measured by: alanine aminotransferase >3.0
             × the upper limit of normal (ULN), aspartate aminotransferase >3.0 × the ULN, or serum
             bilirubin ≥ 1.6 mg/dL at screening, or a clinically significant change in liver
             function between screening and baseline,

          -  Pregnant or lactating female subjects,

          -  Known history of or active alcohol abuse or use of illicit drugs within 1 year prior
             to randomization,

          -  Positive screening for human immunodeficiency virus antibodies, hepatitis B surface
             antigen, or hepatitis C virus antibodies,

          -  Any major surgical procedure within 1 month prior to screening or planned surgical
             procedure during the study period,

          -  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/assent or would confound the secondary objectives of study.