A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx in Participants With Chronic Heart Failure With Reduced Ejection Fraction

Completed · Phase 2 · Has a placebo group

Conditions studied: Chronic Heart Failure With Reduced Ejection Fraction

In brief

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 evaluate the effect of IONIS-AGT-LRx weekly SC injection on plasma AGT concentration and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) levels at each scheduled visit in chronic heart failure participants with reduced ejection fraction (HFrEF).

Key facts

Study ID

NCT04836182

Run by

Ionis Pharmaceuticals, Inc.

People needed

72

Starts

2021-06-08

Expected to finish

2023-01-11

Last updated by the study team

2023-09-11

Who can join

Age: 18 and older, up to 80. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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)

You may not qualify if…

• 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.

Where it is running

• Arkansas Cardiology — Little Rock, Arkansas, United States
• Nature Coast Clinical Research - Crystal River — Crystal River, Florida, United States
• New Generation of Medical Research — Hialeah, Florida, United States
• Michigan Heart — Ypsilanti, Michigan, United States
• St. Louis Heart and Vascular Cardiology — St Louis, Missouri, United States
• The Lindner Center for Research and Education at The Christ Hospital — Cincinnati, Ohio, United States
• South Oklahoma Heart Research — Oklahoma City, Oklahoma, United States
• Newton Clinical Research — Oklahoma City, Oklahoma, United States
• North Texas Research Associates — Allen, Texas, United States
• York Clinical Research LLC — Norfolk, Virginia, United States
• Semmelweis Egyetem - Varosmajori Sziv es Ergyogyaszati Klinika — Budapest, Hungary
• Kardiologiai Maganrendeles es Klinikai Vizsgalohely — Orosháza, Hungary
• Specjalistyczna Praktyka Lekarska — Krakow, Poland
• Samodzielny Publiczny ZOZ Centralny Szpital Kliniczny Uniwersytetu Medycznego — Lodz, Poland
• Indywidualna Specjalistyczna Praktyka Lekarska — Lodz, Poland
• AKA-MED Centrum Spólka z Ograniczona Odpowiedzialnoscia — Ruda Śląska, Poland
• NZOZ Pro Cordis Sopockie Centrum Badan Kardiologicznych — Sopot, Poland
• Centrum Chorob Serca w USK — Wroclaw, Poland
• 4 Wojskowy Szpital Kliniczny z Poliklinika Samodzielny Publiczny ZOZ we Wroclawiu — Wroclaw, Poland

Full record on ClinicalTrials.gov

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