The First-in-Human Study of GW906 Injection

• Age 18-60 years (inclusive) at the time of signing the informed consent form, gender is not restricted.
• BMI 19.0-30.0 kg/m² (inclusive) and weight ≥50 kg during the screening period.
• No use of antihypertensive medications, including ACEIs, ARBs, CCBs, ARNIs, diuretics, etc., within 30 days prior to signing the informed consent form.
• Mean seated SBP measured by AOBP during the screening and baseline periods was 110-159 mmHg (inclusive) and DBP was 70-99 mmHg (inclusive).
• 12-lead electrocardiogram (ECG) results are normal or, according to the investigator, abnormalities are clinically insignificant, and QTcF was \<450 ms for males and \<470 ms for females.
• Before any procedure related to the study begins, the applicant voluntarily signs a written informed consent form, fully understands the purpose and significance of the study, and is willing to comply with the study protocol

Exclusion Criteria:

• Secondary hypertension.
• Orthostatic hypotension (defined as a decrease in SBP ≥20 mmHg or DBP ≥10 mmHg within 1 minute after standing from a supine position).
• History of syncope.
• Metabolic and cardiovascular diseases: ① Diabetes mellitus, or laboratory tests showing fasting blood glucose ≥7.0 mmol/L (126 mg/dL) or glycated hemoglobin (HbA1c) ≥6.5%; ② History of cardiovascular events (e.g., stroke, transient ischemic attack, myocardial infarction, unstable angina, coronary artery bypass grafting, percutaneous coronary intervention, hospitalization for heart failure) or clinically significant valvular heart disease; ③ Other conditions deemed by the investigators to potentially affect the trial or increase the risk to the participants.
• Liver or kidney dysfunction, psychiatric disorders, neurological disorders, tumors, hematological disorders, or other uncontrolled/serious conditions, which the investigator deems may affect trial conduct or increase participant risk.
• Clinically relevant medical history or comorbidities, which the investigator deems may affect trial compliance or data interpretation.
• History of allergy to ≥2 drugs, or known allergy to oligonucleotides or N-acetylgalactosamine (GalNAc).
• History of subcutaneous injection intolerance, or significant abdominal scarring (e.g., due to surgery or burns), which may affect administration of the study drug or assessment of local tolerance.
• Underwent major surgery within 6 months prior to screening, or plans to undergo surgery during the study.
• Lost more than 10% of body weight within 6 months prior to screening, or plans to lose weight during the study.
• History of hospitalization or any clinically significant illness within 3 months prior to randomization, which the investigator deems may affect trial conduct or data interpretation.
• Physical examination and vital signs (excluding blood pressure) results during the screening period are deemed abnormal and clinically significant by the investigator.

• Laboratory test results during the screening period are deemed abnormal and clinically significant by the investigator, including but not limited to:

  1. Creatinine level exceeding the upper limit of normal (ULN), or eGFR \<90 mL/min/1.73 m².
  2. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin, and total bilirubin ≥1.5 times the ULN, deemed abnormal and clinically significant by the investigator.
  3. Serum potassium >5 mmol/L.
• Positive results for hepatitis B surface antigen, hepatitis C virus antibody, human immunodeficiency virus antibody, or Treponema pallidum antibody screening during the screening period.
• Vaccinated within 8 weeks prior to screening, or planned to be vaccinated during the study.
• Individuals who have received the investigational drug or participated in or are currently participating in other clinical trials within 30 days or 5 half-lives (whichever is longer) prior to randomization.
• Individuals who have used, are currently using, or are expected to use, any herbal remedies, supplements, over-the-counter or prescription drugs that affect blood pressure, or other drugs or treatments that the investigator determines may affect the participant's blood pressure or the conduct of the trial within 30 days or 5 half-lives (whichever is longer) prior to administration.
• Women who are pregnant, breastfeeding, or plan to become pregnant during the study period and within one year after administration; women with a positive pregnancy test result at the screening or baseline period; or women of childbearing age who have had unprotected sex with their partner within 14 days prior to or during the screening period.
• The participants or their partners is unwilling to comply with contraceptive requirements (such as complete abstinence, condoms, IUDs, tubal ligation, or other non-pharmacological contraceptive methods) during the study period and within one year after administration.
• Plans to donate sperm or eggs during the study and for 1 year after dosing.
• Alcohol intake ≥14 units per week within 30 days prior to administration of the investigational drug (1 unit = 10g alcohol ≈ 360mL beer/150mL wine/ 45 mL of 40% alcohol-by-volume spirits); or unwillingness to comply with the alcohol restriction requirements during the study period (alcohol intake \<14 units/week, abstinence from alcohol within 24 hours prior to each visit); or a positive breathalyzer test (if a positive breathalyzer test is due to social drinking, a retest may be conducted before D-2 at the investigator's discretion, and the retest result shall prevail).
• Smoking ≥5 cigarettes per day within 3 months prior to screening, or planning to smoke ≥5 cigarettes per day during the study period.
• Positive drug abuse screening (if a false positive is due to methodological reasons, or a positive result is due to drugs (such as influenza or cold medicine), a retest may be conducted before D-2 at the investigator's discretion, and the retest result shall prevail).
• Excessive daily consumption of tea, coffee, and/or caffeinated beverages (≥8 cups/day, 1 cup = 250 mL) within the 3 months prior to randomization, or intake of caffeinated (e.g., coffee, strong tea, cola, chocolate, etc.) or rich in xanthines (animal organs, sardines, soy products, etc.) foods or beverages within 48 hours prior to randomization.
• Receiving a blood transfusion within the 3 months prior to screening, or a total blood donation/loss ≥400 mL; or a total blood donation/loss ≥200 mL within 1 month prior to screening.
• Unwilling or unable to avoid strenuous exercise within 48 hours prior to each blood sample collection.
• Other circumstances deemed unsuitable for participation by the investigator (e.g., circumstances that may cause blood pressure fluctuations or affect the diurnal rhythm of blood pressure)