Eligibility Criteria
Inclusion Criteria:
1. Aged 18 to 65 years (inclusive) at the time of signing the informed consent form (ICF), male or female.
2. Patients diagnosed with essential hypertension.
3. Previously untreated for hypertension, or previously treated with ≤2 types of antihypertensive medications and have undergone at least a 2-week washout period prior to Visit 2 (for long-acting antihypertensive drugs, a 4-week washout period is required, e.g., chlorthalidone, amlodipine, etc.), and meet the following blood pressure measurement criteria:
① During the screening period and at baseline, seated systolic blood pressure (SBP) measured by OBPM is ≥140 mmHg and \<160 mmHg;
② During the screening period, without the use of antihypertensive medications, 24-hour ABPM shows mean SBP ≥130 mmHg and \<160 mmHg.
4. Male subjects with body weight ≥50.0 kg, female subjects with body weight ≥45.0 kg, and Body Mass Index (BMI) between 18.0 and 35.0 kg/m² (inclusive).
5. Maintained a normal diet and salt intake for at least 4 weeks prior to the administration of the investigational product, and has no plans to significantly change diet or body weight during the study.
6. Subjects of childbearing potential, or male subjects with partners of childbearing potential, must agree to use effective contraception from the signing of the ICF until 24 weeks after the administration of the investigational product, and must refrain from donating sperm or eggs.
7. Voluntarily signed a written informed consent form, understands the study procedures and content, is able to communicate effectively with the investigator, and is willing to comply with study-related regulations.
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Exclusion Criteria:
* 1\. Secondary hypertension, including but not limited to renovascular hypertension (unilateral or bilateral renal artery stenosis), coarctation of the aorta, primary aldosteronism, Cushing's syndrome, pheochromocytoma, polycystic kidney disease, or drug-induced hypertension.
2\. During the screening period and at baseline, seated diastolic blood pressure (DBP) measured by OBPM is ≥120 mmHg or \<75 mmHg.
3\. History or current presence of hypotension, orthostatic hypotension, or postural orthostatic tachycardia syndrome (POTS).
4\. Occurrence of cardiovascular or cerebrovascular events within 6 months prior to screening, including but not limited to stroke, transient ischemic attack (TIA), myocardial infarction, unstable angina, coronary artery bypass graft (CABG) surgery, percutaneous coronary intervention (PCI), or hospitalization due to heart failure.
5\. Presence of congestive heart failure (New York Heart Association \[NYHA\] functional class III-IV), or clinically significant valvular heart disease or arrhythmia (e.g., persistent atrial fibrillation) as determined by the investigator.
6\. Diagnosis of congenital long QT syndrome, family history of congenital long QT syndrome, or presence of an implanted pacemaker or automatic implantable cardioverter-defibrillator (AICD).
7\. Presence of clinically significant electrocardiogram (ECG) abnormalities as judged by the investigator at screening.
8\. Comorbid type 1 diabetes at screening, or poorly controlled type 2 diabetes (Glycated Hemoglobin \[HbA1c\] \>9.0%).
9\. Comorbid chronic liver disease, including but not limited to liver fibrosis and cirrhosis.
10\. Diagnosis of malignancy, or a history of malignancy within 5 years prior to signing the ICF (except for cured non-melanoma skin cancer and cervical intraepithelial neoplasia with no signs of recurrence).
11\. Accompanied by other severe, progressive, or uncontrolled diseases, including but not limited to diseases of the endocrine, hematological, urinary, hepatobiliary, respiratory, neurological, cardiovascular, gastrointestinal systems, or infectious diseases, wherein the investigator assesses that participation in the study would increase the risk to the subject.
12\. Positive for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV-Ab), Treponema pallidum antibody (TP-Ab), or Human Immunodeficiency Virus antibody (HIV-Ab) at screening.
13\. Laboratory abnormalities during the screening period as follows:
1. Platelet count \<100×10⁹/L;
2. Hemoglobin \<90 g/L;
3. eGFR \<60 mL/min/1.73 m² (calculated by CKD-EPI 2021 equation);
4. Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) \>1.5×ULN;
5. Total Bilirubin (TBIL) \>2×ULN (for subjects with Gilbert's syndrome, TBIL \>3×ULN);
6. Serum potassium \>1.0×ULN. 14. Known allergy to oligonucleotides, drugs containing N-acetylgalactosamine (GalNAc), the investigational product used in this trial and its components, or drugs of the same class.
15\. Presence of tattoos, scars, or birthmarks on the abdomen, upper arm, or thigh that may affect the assessment of injection site reactions.
16\. Undergone major surgery within 3 months prior to the administration of the investigational product, or planning to undergo elective surgery during the study period.
17\. Donated blood or experienced significant blood loss (≥400 mL) within 3 months prior to the administration of the investigational product (excluding menstrual bleeding in females), or received a blood transfusion within 12 months prior to the administration of the investigational product.
18\. Received a live vaccine within 4 weeks prior to the administration of the investigational product, or planning to receive a live vaccine during the study period.
19\. Use of any antisense oligonucleotide (ASO) or small interfering RNA (siRNA) drugs within 12 months prior to the administration of the investigational product.
20\. History of drug or substance abuse, or positive urine drug abuse screening during the screening period.
21\. Smoking history of ≥5 cigarettes per day within 3 months prior to screening, or plan to smoke ≥5 cigarettes per day during the study period after signing the ICF.
22\. Alcohol intake of ≥14 units/week within 4 weeks prior to screening (1 unit = 10 g of alcohol, ≈360 mL of beer / 150 mL of wine / 45 mL of 40% spirits), or unwillingness to comply with alcohol restriction requirements during the study period after signing the ICF (alcohol consumption \<14 units/week, abstinence from alcohol for 24 hours prior to each visit), or positive alcohol breath test during screening.
23\. Consumed caffeine-containing beverages (e.g., coffee, tea, caffeinated soda, and cola) within 2 days prior to the administration of the investigational product, or unwillingness to comply with requirements regarding caffeine beverage intake during the study period after signing the ICF (\<5 cups of coffee/day).
24\. Participation in other clinical trials within 3 months prior to the administration of the investigational product, or currently participating in other clinical trials (subjects may be enrolled in this study if they withdrew from the previous study before treatment, i.e., were not randomized or did not receive treatment).
25\. Pregnant or lactating women. 26. Individuals whose job nature requires night shifts, early shifts, or rotating shifts, which may lead to blood pressure fluctuations or affect circadian blood pressure rhythms.
27\. Use or planned use of other antihypertensive drugs (e.g., beta-blockers, phosphodiesterase-5 inhibitors) from the signing of the ICF until 24 weeks after receiving the investigational product, except for protocol-permitted antihypertensive treatments and the investigational product.
28\. Any other condition judged by the investigator to make the subject unsuitable for participation in this clinical trial.