Single Ascending Doses of GGF2 in Patients With Left Ventricular Dysfunction and Symptomatic Heart Failure

Study Overview
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Brief Summary
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Study to determine the safety, tolerability, pharmacokinetics and immunogenicity of single intravenous administrations of GGF2 in patients with heart failure.

Detailed Description
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Phase 1, double-blind, placebo-controlled, dose escalation study to determine the safety, tolerability, pharmacokinetics and immunogenicity of single intravenous administrations of GGF2 in cohorts of patients with left ventricular dysfunction and symptomatic heart failure.

Official Title
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A Phase 1, Double-Blind, Placebo-Controlled Study of Single Ascending Doses of GGF2 in Patients With Left Ventricular Dysfunction and Symptomatic Heart Failure

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Glial growth factor 2/ Neuregulin 1β3
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Left ventricular ejection fraction (LVEF) between 10% and 40%. Male or female, aged 18 to 75 years, inclusive. Exclusion Criteria: Received any investigational agent or participation in any clinical study of an investigational agent or investigational therapy up to 30 days prior to the screening visit. Use of any new prescription medication up to 14 days prior to receiving investigational drug. Patients with known specific hepatic disease; bilirubin >2 mg/dL, SGOT > 100 IU. Patients with a history of hepatic impairment (hepatitis B and C). Serum creatinine >2.5 mg/dL. Documented stroke or transient ischemic attack (TIA) within 60 days of study enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: GGF2<br>Seven dosing cohorts: 2 patients randomized to receive 1 GGF2, 1 placebo; if no drug-related dose-limiting toxicities in GGF2-treated patient, other 4 patients in cohort will be randomized (3:1) and dosed | Drug: Glial growth factor 2/ Neuregulin 1β3<br> <br> * Other names: Recombinant Human Glial Growth Factor 2;Other: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of Single Ascending Doses of GGF2 Via an Assessment of the Toxicology Profile as Measured by Treatment Emergent Adverse Events (TEAEs) | Safety/ tolerability of single dose; cumulative safety over 6 months TEAEs are defined as adverse events with date of onset (or worsening) on or after the start date of double-blind treatment and no more than 28 days from the start date of double-blind treatment. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline of Two-Dimensional Echocardiogram (2D-ECHO) Measured by Ejection Fraction (EF) | An echocardiogram is a type of ultrasound test that uses high-pitched sound waves that are sent through a device called a transducer. The device picks up echoes of the sound waves as they bounce off the different parts of your heart. These echoes are turned into moving pictures of your heart that can be seen on a video screen.¹ Ejection fraction is a measurement of the percentage of blood leaving your heart each time it contracts.² ¹http://wakeinternalmedicine.com/services-and-procedures/services/radiology/2d-echo/ ²http://www.mayoclinic.org/ejection-fraction/expert-answers/faq-20058286 | Screening, day 8, day 14, day 28, and 3 months post-dose | 
| Change From Baseline of 2D-ECHO Measured by End-Diastolic Volume (EDV) | EDV is the amount of blood in the ventricle immediately before a cardiac contraction begins; used as a measurement of diastolic function.¹ ¹http://medical-dictionary.thefreedictionary.com/end-diastolic+volume | Screening, day 8, day 14, day 28, and 3 months post-dose | 
| Change From Baseline of 2D-ECHO Measured by End-Systolic Volume (ESV) | ESV is the volume of blood remaining in each ventricle at the end of systole.¹ ¹http://medical-dictionary.thefreedictionary.com/end-diastolic+volume | Screening, day 8, day 14, day 28, and 3 months post-dose |