a study to assess the safety, tolerability and efficacy of ionis-agt-lrx in hypertensive participants with uncontrolled blood pressure

Conditions: Hypertension

Summary: the purpose of this study was to evaluate the effect of ionis-agt-lrx compared to placebo on seated automated office systolic blood pressure (sbp) from baseline to study day 85 in uncontrolled hypertensive participants on ≥ 3 antihypertensive medications and to evaluate the effect of ionis-agt-lrx on ambulatory blood pressure, seated automated office sbp, seated automated office diastolic blood pressure (dbp), and plasma angiotensinogen (agt) at each scheduled visit in uncontrolled hypertensive participants on ≥ 3 antihypertensive medications.

this was a phase 2, double-blind, randomized, placebo-controlled study in up to 160 participants. participants were randomized in a 2:1 ratio and received a once-weekly subcutaneous (sc) treatment with either ionis-agt-lrx or matching placebo. the length of participation in the study was approximately 31 weeks, which included an up to 6-week screening period, a 12-week treatment period, and a 13-week post-treatment period.

Eligibility criteria:
inclusion criteria: * males or females aged 18-80 inclusive and weighing ≥ 50 kilograms (kg) at the time of informed consent * females: must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal * males must be abstinent, surgically sterile or if engaged in sexual relations with a woman of childbearing potential (wocbp), a highly effective contraceptive method must be used * body mass index (bmi) ≤ 45.0 kilograms per square meter (kg/m\^2) * at screening, the participant must have been on a stable, maximally tolerated regimen (per investigator judgement) of 3 or more antihypertensive medications for at least 1 month prior to screening and will be required to maintain this regimen throughout the study. the combination of antihypertensive medications must be in the following categories: a) angiotensin-converting enzyme inhibitor (acei) or angiotensin ii receptor blocker (arb), b) beta blocker: c) calcium channel blocker d) diuretic, e) alpha-1 blocker f) centrally acting sympatholytic agent or g) direct acting vasodilators (e.g. hydralazine) exclusion criteria: * clinically significant abnormalities in screening laboratory results, medical history according to investigator judgment * history of secondary hypertension (htn) including, but not limited to any of the following: renovascular htn (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary hyperaldosteronism, cushing's disease, pheochromocytoma, polycystic kidney disease, and drug-induced htn * the use of the following at time of screening and during the course of the study: * other medications for the treatment of htn (e.g., minoxidil, diazoxide, renin inhibitors) * medications that may cause hyperkalemia unless on a stable dose at least 1 month prior to the screening visit and no known history of hyperkalemia per investigator judgement * use of oral anticoagulants, unless stable for 4 weeks prior to the first dose of study drug and regular monitoring must be performed per clinical practice during the study unless the participant is receiving vitamin k agonists. if the participant is receiving vitamin k antagonists (e.g., warfarin) international normalized ratio (inr) should be in therapeutic range, as established by the investigator, for 4 weeks prior to the first dose * chronic administration of non-steroidal anti-inflammatory drugs (nsaids) or cyclooxygenase 2 (cox-2) inhibitors (except aspirin for cardiovascular disease provided the total daily dose does not exceed 325 mg) * history of bleeding diathesis, coagulopathy, immune thrombocytopenic purpura (itp), thrombotic cytopenic purpura (ttp), or any qualitative or quantitative platelet defect * unstable/underlying known cardiovascular disease defined as: * any history of congestive heart failure (new york heart association \[nyha\] class iii-iv) * any history of previous myocardial infarction, coronary revascularization, unstable or stable angina pectoris ˂ 1 year prior to screening * any hemodynamically unstable atrial or ventricular arrhythmias * significant uncorrected valvular heart disease * any history of stroke or transient ischemic attack \< 1 year prior to screening * a cardiac valve repair, cardiac device implantation, and/or a hospitalization for heart failure within 3 months of screening * participant works nighttime shifts (e.g., 11 pm to 7 am)

Keywords: hypertension hypertensive agt angiotensinogen blood pressure