Study to Assess the Safety, Tolerability and PK/PD After... | NCT02808585

NCT02808585

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
PB1046 Injection, 0.2 mg/kg	Experimental	Four weekly doses of PB1046 Injection, 0.2 mg/kg	Drug: PB1046 Injection
PB1046 Injection, 0.4 mg/kg	Experimental	Four weekly doses of PB1046 Injection, 0.4 mg/kg	Drug: PB1046 Injection
PB1046 Injection, 0.6 mg/kg	Experimental	Four weekly doses of PB1046 Injection, 0.6 mg/kg	Drug: PB1046 Injection
PB1046 Injection, 1.2 mg/kg	Experimental	Four weekly doses of PB1046 Injection, 1.2 mg/kg	Drug: PB1046 Injection
Placebo Comparator	Placebo Comparator	Four weekly doses of Placebo (0.9% NaCl) Injection	Drug: Placebo Injection

Interventions

Name	Type	Description	Arm Group Labels	Other Names
PB1046 Injection	Drug	Four weekly subcutaneous injections of PB1046.	PB1046 Injection, 0.2 mg/kg PB1046 Injection, 0.4 mg/kg PB1046 Injection, 0.6 mg/kg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Telemetry	Number of participants with rhythm abnormalities as assessed by continuous mobile telemetry monitoring.	Up to six weeks starting 7 to 10 days before first dose.
12-Lead ECG Assessment - Incidence of Clinically Significant Findings	Number of participants with a clinically significant change from baseline in 12-Lead ECG and presence of rhythm abnormalities and relationship to exposure of PB1046 compared to placebo	Seven weeks starting the first week of dosing.
12-Lead ECG - Categorical Analysis of QT/QTc Interval - Participants With Clinically Significant Findings	Number of participants with a clinically significant change from baseline in 12-Lead ECG and presence or absence of rhythm abnormalities and relationship to exposure of PB1046 compared to placebo	Seven weeks starting the first week of dosing.
Laboratory Parameters - Serum Chemistry - Participants With Clinically Significant Findings	Number of participants with clinically significant changes from baseline in laboratory parameters (serum chemistry) and the relationship to PB1046 compared to placebo	Eight weeks starting one week before first dose.
Laboratory Parameters - Hematology - Participants With Clinically Significant Findings	Number of participants with clinically significant changes from baseline in laboratory parameters (hematology) and the relationship to PB1046 compared to placebo	Eight weeks starting one week before first dose.
Laboratory Parameters - Urinalysis - Participants With Clinically Significant Findings

Secondary Outcomes

Measure	Description	Time Frame
Pharmacokinetic Profile - Area Under the Curve Over the Dosing Interval [AUC(0-t)]	Comparison of dose exposures [AUC(0-t)] during once weekly administration of various doses of PB1046	Pre-dose, Day 1 post-dose (1, 3, 24, 48, 72, 120 hours post-dose 1), Day 7, 14, 21 (1, 3, 24, 48, 72, 120 hours post-dose 4), Day 22, 23, 24, 26, 28, 29, 30, and 31.

Eligibility Module

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.

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Pinnacle Research Group, LLC		Anniston	Alabama	36207	United States
Phoenix Medical Research

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
FG001	PB1046 Injection, 0.4 mg/kg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 17, 2016	Mar 17, 2022

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

PB1046 Injection, 1.2 mg/kg

Number of participants with clinically significant changes from baseline in laboratory parameters (urinalysis) and the relationship to PB1046 compared to placebo

Four weekly doses of PB1046 Injection, 0.4 mg/kg

PB1046 Injection: Four weekly subcutaneous injections of PB1046.

Safety/Intent-to-Treat/Per Protocol Population

Arm/Group Information

ID	Title	Description
BG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
BG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
BG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
BG003	PB1046 Injection, 1.2 mg/kg	Four weekly doses of PB1046 Injection, 1.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
BG004	Placebo Comparator	Four weekly doses of Placebo (0.9% NaCl) Injection Placebo Injection: Four weekly subcutaneous injections of placebo.
BG005	Total	Total of all reporting groups

Units	Counts
Participants	BG0003 BG0016 BG0027 BG0036 BG0047 BG00529

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00060.7± 13.01 BG00169.7± 10.89 BG00267.6± 11.27 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0002 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG0003 BG0016 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Telemetry

Number of participants with rhythm abnormalities as assessed by continuous mobile telemetry monitoring.

Safety/Intent-to-Treat/Per Protocol Population

Posted

Count of Participants

Participants

Up to six weeks starting 7 to 10 days before first dose.

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg	Four weekly doses of PB1046 Injection, 1.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG004	Placebo Comparator	Four weekly doses of Placebo (0.9% NaCl) Injection Placebo Injection: Four weekly subcutaneous injections of placebo.

Units	Counts
Participants	OG0003 OG0016 OG0026 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Primary

12-Lead ECG Assessment - Incidence of Clinically Significant Findings

Number of participants with a clinically significant change from baseline in 12-Lead ECG and presence of rhythm abnormalities and relationship to exposure of PB1046 compared to placebo

Safety/Intent-to-Treat/Per Protocol Population

Posted

Count of Participants

Participants

Seven weeks starting the first week of dosing.

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg	Four weekly doses of PB1046 Injection, 1.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.

Primary

12-Lead ECG - Categorical Analysis of QT/QTc Interval - Participants With Clinically Significant Findings

Number of participants with a clinically significant change from baseline in 12-Lead ECG and presence or absence of rhythm abnormalities and relationship to exposure of PB1046 compared to placebo

Safety/Intent-to-Treat/Per Protocol Population

Posted

Count of Participants

Participants

Seven weeks starting the first week of dosing.

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg

Primary

Laboratory Parameters - Serum Chemistry - Participants With Clinically Significant Findings

Number of participants with clinically significant changes from baseline in laboratory parameters (serum chemistry) and the relationship to PB1046 compared to placebo

Safety/Intent-to-Treat/Per Protocol Population

Posted

Count of Participants

Participants

Eight weeks starting one week before first dose.

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg	Four weekly doses of PB1046 Injection, 1.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.

Primary

Laboratory Parameters - Hematology - Participants With Clinically Significant Findings

Number of participants with clinically significant changes from baseline in laboratory parameters (hematology) and the relationship to PB1046 compared to placebo

Safety/Intent-to-Treat/Per Protocol Population

Posted

Count of Participants

Participants

Eight weeks starting one week before first dose.

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg	Four weekly doses of PB1046 Injection, 1.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.

Primary

Laboratory Parameters - Urinalysis - Participants With Clinically Significant Findings

Number of participants with clinically significant changes from baseline in laboratory parameters (urinalysis) and the relationship to PB1046 compared to placebo

Safety/Intent-to-Treat/Per Protocol Population

Posted

Count of Participants

Participants

Eight weeks starting one week before first dose.

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg	Four weekly doses of PB1046 Injection, 1.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.

Primary

Laboratory Parameters - eGFR

Changes from baseline in laboratory parameters (eGFR) and the relationship to PB1046 compared to placebo.

Calculated using Chronic Kidney Disease Epidemiology Collaboration Equation (CKD-EPI)

Safety/Intent-to-Treat/Per Protocol Population. One subject at 0.6 mg/kg dose missed sample collection and was excluded from analysis.

Posted

Mean

Standard Deviation

mL/min/1.73m^2

Baseline, Week 2, 3, 4, 5 and 8.

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg

Primary

Laboratory Parameters - Lipid Profile - Participants With Clinically Significant Findings

Number of participants with clinically significant changes from baseline in laboratory parameters (lipid profile) and the relationship to PB1046 compared to placebo

Posted

Count of Participants

Participants

Eight weeks starting one week before first dose (Baseline and at Week 8).

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg	Four weekly doses of PB1046 Injection, 1.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.

Primary

Vital Signs - Systolic Blood Pressure

Changes from baseline in vital signs (systolic blood pressure) and the relationship to PB1046 compared to placebo.

Safety/Intent-to-Treat/Per Protocol Population

Posted

Mean

Standard Deviation

mmHg

Baseline, Day 0, Day 1, 2, 3, 5, 7, 14, 21, 22, 23, 24, 26, 28, 29, 30, 31, and 49.

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg	Four weekly doses of PB1046 Injection, 1.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.

Primary

Vital Signs - Heart Rate

Changes from baseline in vital signs (heart rate) and the relationship to PB1046 compared to placebo.

Safety/Intent-to-Treat/Per Protocol Population

Posted

Mean

Standard Deviation

Beats/min

Baseline, Day 0, Day 1, 2, 3, 5, 7, 14, 21, 22, 23, 24, 26, 28, 29, 30, 31, and 49.

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg	Four weekly doses of PB1046 Injection, 1.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.

Primary

Vital Signs - Temperature

Changes from baseline in vital signs (temperature) and the relationship to PB1046 compared to placebo.

Safety/Intent-to-Treat/Per Protocol Population

Posted

Mean

Standard Deviation

Celsius

Baseline, Day 0, Day 1, 2, 3, 5, 7, 14, 21, 22, 23, 24, 26, 28, 29, 30, 31, and 49.

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg	Four weekly doses of PB1046 Injection, 1.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.

Primary

Vital Signs - Respiratory Rate

Changes from baseline in vital signs (respiratory rate) and the relationship to PB1046 compared to placebo.

Safety/Intent-to-Treat/Per Protocol Population

Posted

Mean

Standard Deviation

Breaths/min

Baseline, Day 0, Day 1, 2, 3, 5, 7, 14, 21, 22, 23, 24, 26, 28, 29, 30, 31, and 49.

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg	Four weekly doses of PB1046 Injection, 1.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.

Primary

Vital Signs - Diastolic Blood Pressure

Changes from baseline in vital signs (systolic blood pressure) and the relationship to PB1046 compared to placebo.

Safety/Intent-to-Treat/Per Protocol Population

Posted

Mean

Standard Deviation

mmHg

Baseline, Day 0, Day 1, 2, 3, 5, 7, 14, 21, 22, 23, 24, 26, 28, 29, 30, 31, and 49.

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg	Four weekly doses of PB1046 Injection, 1.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.

Secondary

Pharmacokinetic Profile - Area Under the Curve Over the Dosing Interval [AUC(0-t)]

Comparison of dose exposures [AUC(0-t)] during once weekly administration of various doses of PB1046

Safety/Intent-to-Treat/Per Protocol Population. Only subjects with sufficient data analyzed.

Posted

Mean

Standard Error

h*ng/mL

Pre-dose, Day 1 post-dose (1, 3, 24, 48, 72, 120 hours post-dose 1), Day 7, 14, 21 (1, 3, 24, 48, 72, 120 hours post-dose 4), Day 22, 23, 24, 26, 28, 29, 30, and 31.

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg

Secondary

Pharmacokinetic Profile - Maximum Serum Concentration (Cmax)

Comparison of dose exposures (Cmax) during once weekly administration of various doses of PB1046

Safety/Intent-to-Treat/Per Protocol Population. Only subjects with sufficient data analyzed.

Posted

Mean

Standard Error

ng/mL

Pre-dose, Day 1 post-dose (1, 3, 24, 48, 72, 120 hours post-dose 1), Day 7, 14, 21 (1, 3, 24, 48, 72, 120 hours post-dose 4), Day 22, 23, 24, 26, 28, 29, 30, and 31.

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg

Secondary

Pharmacokinetic Profile - Time to Cmax (Tmax)

Comparison of dose exposures (Tmax) during once weekly administration of various doses of PB1046

Safety/Intent-to-Treat/Per Protocol Population. Only subjects with sufficient data analyzed.

Posted

Mean

Standard Error

hours

Pre-dose, Day 1 post-dose (1, 3, 24, 48, 72, 120 hours post-dose 1), Day 7, 14, 21 (1, 3, 24, 48, 72, 120 hours post-dose 4), Day 22, 23, 24, 26, 28, 29, 30, and 31.

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg

Secondary

Pharmacokinetic Profile - Elimination Rate Constant (Lambda z)

Comparison of dose exposures (lambda z) during once weekly administration of various doses of PB1046

Safety/Intent-to-Treat/Per Protocol Population. Only subjects with sufficient data analyzed.

Posted

Mean

Standard Error

1/hour

Pre-dose, Day 1 post-dose (1, 3, 24, 48, 72, 120 hours post-dose 1), Day 7, 14, 21 (1, 3, 24, 48, 72, 120 hours post-dose 4), Day 22, 23, 24, 26, 28, 29, 30, and 31.

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg

Secondary

Pharmacokinetic Profile - Elimination Half-life (t½)

Comparison of dose exposures (t½) during once weekly administration of various doses of PB1046

Safety/Intent-to-Treat/Per Protocol Population. Only subjects with sufficient data analyzed.

Posted

Mean

Standard Error

hours

Pre-dose, Day 1 post-dose (1, 3, 24, 48, 72, 120 hours post-dose 1), Day 7, 14, 21 (1, 3, 24, 48, 72, 120 hours post-dose 4), Day 22, 23, 24, 26, 28, 29, 30, and 31.

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg

Secondary

Pharmacokinetic Profile - Clearance (CL/F), Uncorrected for Bioavailability

Comparison of dose exposures (CL/F) during once weekly administration of various doses of PB1046

Safety/Intent-to-Treat/Per Protocol Population. Only subjects with sufficient data analyzed.

Posted

Mean

Standard Error

mL/h/kg

Pre-dose, Day 1 post-dose (1, 3, 24, 48, 72, 120 hours post-dose 1), Day 7, 14, 21 (1, 3, 24, 48, 72, 120 hours post-dose 4), Day 22, 23, 24, 26, 28, 29, 30, and 31.

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg

Secondary

Pharmacokinetic Profile - Volume of Distribution (Vz/F), Uncorrected for Bioavailability (F)

Comparison of dose exposures (Vz/F) during once weekly administration of various doses of PB1046

Safety/Intent-to-Treat/Per Protocol Population. Only subjects with sufficient data analyzed.

Posted

Mean

Standard Error

mL/kg

Pre-dose, Day 1 post-dose (1, 3, 24, 48, 72, 120 hours post-dose 1), Day 7, 14, 21 (1, 3, 24, 48, 72, 120 hours post-dose 4), Day 22, 23, 24, 26, 28, 29, 30, and 31.

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg

Secondary

Immunogenicity

Number of participants reporting positive immunogenicity (four-fold increase of pre-dose titer)

Safety/Intent-to-Treat/Per Protocol Population

Posted

Number

subjects

Eleven weeks starting the first week of dosing.

ID	Title	Description
OG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.
OG003	PB1046 Injection, 1.2 mg/kg	Four weekly doses of PB1046 Injection, 1.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	PB1046 Injection, 0.2 mg/kg	Four weekly doses of PB1046 Injection, 0.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.	3	0	3	3	3
EG001	PB1046 Injection, 0.4 mg/kg	Four weekly doses of PB1046 Injection, 0.4 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.	6	1	6	6	6
EG002	PB1046 Injection, 0.6 mg/kg	Four weekly doses of PB1046 Injection, 0.6 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.	7	0	7	7	7
EG003	PB1046 Injection, 1.2 mg/kg	Four weekly doses of PB1046 Injection, 1.2 mg/kg PB1046 Injection: Four weekly subcutaneous injections of PB1046.	6	0	6	6	6
EG004	Placebo Comparator	Four weekly doses of Placebo (0.9% NaCl) Injection Placebo Injection: Four weekly subcutaneous injections of placebo.	7	0	7	0	7

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	Systematic Assessment	EG0003 at risk EG0011 affected6 at risk EG0027 at risk EG0036 at risk EG0047 at risk
Blood creatinine increased	Cardiac disorders	Systematic Assessment	EG0003 at risk EG0011 affected6 at risk EG0027 at risk EG003
White blood cell count	Cardiac disorders	Systematic Assessment	EG0003 at risk EG0011 affected6 at risk EG0027 at risk EG003

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG0030 events0 affected6 at risk EG0040 events0 affected7 at risk
Hypersensitivity	Immune system disorders	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Burning sensation	Nervous system disorders	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Dizziness	Nervous system disorders	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0023 events1 affected7 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Dizziness	Vascular disorders	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Flushing	Vascular disorders	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003
Orthostatic hypotension	Vascular disorders	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected6 at risk EG0022 events2 affected7 at risk EG003
Injection site erythema	General disorders	Systematic Assessment	EG00020 events3 affected3 at risk EG00140 events6 affected6 at risk EG00234 events7 affected7 at risk EG003
Injection site induration	General disorders	Systematic Assessment	EG0000 events0 affected3 at risk EG0013 events2 affected6 at risk EG0023 events2 affected7 at risk EG003
Injection site pain	General disorders	Systematic Assessment	EG0009 events2 affected3 at risk EG0015 events2 affected6 at risk EG00210 events2 affected7 at risk EG003
Injection site pruritus	General disorders	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected7 at risk EG003
Injection site swelling	General disorders	Systematic Assessment	EG0004 events1 affected3 at risk EG0014 events2 affected6 at risk EG0025 events4 affected7 at risk EG003
Injection site warmth	General disorders	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0021 events1 affected7 at risk EG003
Malaise	General disorders	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected6 at risk EG0020 events0 affected7 at risk EG003

ID	Term
D006333	Heart Failure

ID	Term
C000706508	VIP-ELP fusion molecule PB1046

Four weekly doses of PB1046 Injection, 1.2 mg/kg

PB1046 Injection: Four weekly subcutaneous injections of PB1046.

Four weekly doses of PB1046 Injection, 1.2 mg/kg

PB1046 Injection: Four weekly subcutaneous injections of PB1046.

Four weekly doses of PB1046 Injection, 1.2 mg/kg

PB1046 Injection: Four weekly subcutaneous injections of PB1046.

Four weekly doses of PB1046 Injection, 1.2 mg/kg

PB1046 Injection: Four weekly subcutaneous injections of PB1046.

Four weekly doses of PB1046 Injection, 1.2 mg/kg

PB1046 Injection: Four weekly subcutaneous injections of PB1046.

Four weekly doses of PB1046 Injection, 1.2 mg/kg

PB1046 Injection: Four weekly subcutaneous injections of PB1046.

Four weekly doses of PB1046 Injection, 1.2 mg/kg

PB1046 Injection: Four weekly subcutaneous injections of PB1046.

EG0040 events0 affected7 at risk

ID	Term
D006331	Heart Diseases
D002318	Cardiovascular Diseases