Status:
COMPLETED
A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx in Participants With Chronic Heart Failure With Reduced Ejection Fraction
Lead Sponsor:
Ionis Pharmaceuticals, Inc.
Conditions:
Chronic Heart Failure With Reduced Ejection Fraction
Eligibility:
All Genders
18-80 years
Phase:
PHASE2
Brief Summary
The purpose of this study is to evaluate the effect of IONIS-AGT-LRX weekly subcutaneous (SC) injection on plasma angiotensinogen (AGT) concentration from Baseline to Study Day 85 (Week 13) and to eva...
Detailed Description
This study will be a Phase 2, double-blind, randomized, placebo-controlled study in up to 72 participants. Participants will be randomized in a 2:1 ratio to either IONIS-AGT-LRX or matching placebo an...
Eligibility Criteria
Inclusion
- 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
- Screening NT-proBNP ≥ 600 picograms per milliliter (pg/mL) and less than (\<) 8500 pg/mL
- Established diagnosis of heart failure (HF) with reduced systolic function for at least 6 months prior to the screening visit (left ventricular ejection fraction, \[LVEF\] ≤ 40%
- New York Heart Association class I-III
- Participants should receive background standard of care for HFrEF. Therapy should have been individually optimized and stable for ≥ 4 weeks before randomization and include:
- An angiotensin-converting-enzyme inhibitor (ACEi), or angiotensin II receptor blockers (ARBs) or sacubitril/valsartan (mandatory)
- A beta-blocker (unless contraindicated or not tolerated)
- A mineralocorticoid receptor antagonist (MRA, unless contraindicated or not tolerated)
Exclusion
- HF due to restrictive cardiomyopathy, active myocarditis, chemotherapy, hypertrophic cardiomyopathy, primary cardiac valve disease, non-compaction cardiomyopathy, or takotsubo cardiomyopathy.
- 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.
- Symptomatic hypotension or systolic blood pressure (SBP) ≤ 90 millimeters of mercury (mmHg) at screening.
- Uncontrolled hypertension (HTN) (SBP \> 160 mmHg or diastolic blood pressure (BP) \> 100 mmHg) prior to screening.
- Heart transplant, and/or Left Ventricular Assist Device (LVAD) prior to screening or anticipated heart transplant or LVAD during the study.
- Implantation of a cardiac resynchronization therapy device (CRT) within 3 months prior screening or intent to implant a CRT within 3 months after screening.
- 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.
- Coronary, valve or carotid artery disease likely to require surgical or percutaneous intervention within the 3 months after screening.
- Severe pulmonary disease with any of the following:
- Requirement of continuous (home) oxygen or
- Known diagnosis of severe chronic obstructive pulmonary disease (as defined by the American Thoracic Society/European Respiratory Society) or severe restrictive lung disease, in the opinion of the investigator.
- 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.
- Alanine aminotransferase/aspartate aminotransferase (ALT/AST) \> 2.0 × upper limit of normal (ULN).
- Total bilirubin ≥ 1.5 × ULN (participants with total bilirubin ≥ 1.5 × ULN may be allowed on study if indirect bilirubin only is elevated, ALT/AST is not greater than the ULN, and known to have Gilbert's disease).
- Platelets \< 100,000/millimeter\^3 (mm\^3).
- Urine protein creatinine ratio (UPCR) ≥ 500 milligrams per gram (mg/g).
- Hemoglobin A1c (HbA1c) \> 9.5% or uncontrolled diabetes per investigator judgement.
- Estimated glomerular filtration rate (eGFR) \< 30 milliliters/ minute /1.73 m\^2 (mL/min/1.73 meter\^2) at screening.
- Abnormal thyroid function tests with clinical significance per investigator judgement.
- Serum potassium \> 5.1 millimoles per liter (mmol/L) at screening.
- Requirement of treatment with both ACEi and ARBs.
- Previous history of intolerance to ACEi or ARBs or history of hyperkalemia.
Key Trial Info
Start Date :
June 8 2021
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
January 11 2023
Estimated Enrollment :
72 Patients enrolled
Trial Details
Trial ID
NCT04836182
Start Date
June 8 2021
End Date
January 11 2023
Last Update
September 11 2023
Active Locations (19)
Enter a location and click search to find clinical trials sorted by distance.
1
Arkansas Cardiology
Little Rock, Arkansas, United States, 72205
2
Nature Coast Clinical Research - Crystal River
Crystal River, Florida, United States, 34429
3
New Generation of Medical Research
Hialeah, Florida, United States, 33016
4
Michigan Heart
Ypsilanti, Michigan, United States, 48197