Chronic Heart Failure with Reduced Ejection Fraction MedDRA version: 20.0 Level: LLT Classification code 10008908 Term: Chronic heart failure System Organ Class: 100000004849
Conditions
Interventions
Product Name: ISIS 757456
Product Code: ISIS 757456
Pharmaceutical Form: Solution for injection
Current Sponsor code: ISIS 757456
Other descriptive name: ISIS 757456
Concentration unit: mg/ml milligra
Sponsors
Ionis Pharmaceuticals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Satisfy the following: Females must be non-pregnant and non-lactating and of non-childbearing potential. Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential (WOCBP), she must be willing to use a highly effective contraceptive method 2. Screening NT-proBNP = 600 picograms per milliliter (pg/mL) and less than (=65 years) yes F.1.3.1 Number of subjects for this age range 47
Exclusion criteria
Exclusion criteria: 1. Any cause of chronic HF other than ischemic cardiomyopathy and dilated cardiomyopathy 2. Acute decompensated HF requiring intravenous (IV) diuretics, IV inotropes or IV vasodilators with discharge date within 30 days of screening or acute mechanical support (e.g., intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device) with discharge date within 90 days of screening. 3. Symptomatic hypotension or systolic blood pressure (SBP) = 90 millimeters of mercury (mmHg) at screening. 4. Heart transplant, and/or Left Ventricular Assist Device (LVAD) prior to screening or anticipated heart transplant or LVAD during the study. 5. Implantation of a cardiac resynchronization therapy device (CRT) within 3 months prior screening or intent to implant a CRT within 3 months after screening. 6. Acute coronary syndrome, unstable angina, stroke, transient ischemic attack (TIA), coronary revascularization, cardiac device implantation, cardiac valve repair, carotid or other major surgery within 3 months of screening. 7. Coronary, valve or carotid artery disease likely to require surgical or percutaneous intervention within the 3 months after screening. 8. Screening laboratory results as follows, or any other clinically significant abnormalities in screening laboratory values that would render a participant unsuitable for inclusion in the opinion of the investigator. a. Estimated glomerular filtration rate (eGFR) 4.7 millimoles per liter (mmol/L) at screening. 9. Requirement of treatment with both ACEi and ARBs. 10. Previous history of intolerance to ACEi or ARBs or history of hyperkalemia.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of ISIS 757456 weekly subcutaneous (SC) injection on plasma angiotensinogen (AGT) concentration from Baseline to Study Day 85 (Week 13) in patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF);Secondary Objective: To evaluate the effect of ISIS 757456 weekly SC injection on plasma angiotensinogen (AGT) concentration at each scheduled visit in patients with chronic HFrEF To evaluate the effect of ISIS 757456 on N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) at each scheduled visit in patients with chronic HFrEF ;Primary end point(s): Percent change in plasma AGT from Baseline to Study Day 85 (Week 13);Timepoint(s) of evaluation of this end point: Percent change in plasma AGT from Baseline to Study Day 85 (Week 13) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Absolute levels and change and percent change in plasma AGT from Baseline to each scheduled, post-baseline visit • Absolute level, change, within group changes, and percent change in NT-proBNP, from Baseline to each scheduled, post-baseline visit ;Timepoint(s) of evaluation of this end point: From Baseline to each scheduled, post-baseline visit | — |
Countries
Hungary, Poland, United States
Contacts
Public ContactIonis Clinical Trial Information
Ionis Pharmaceuticals, Inc.
Outcome results
None listed