Hypertension
Conditions
Interventions
YKYY029 injection group(Cohort A):YKYY029 150mg
Dosage and Administration: Participants shall be assigned to corresponding dosage groups A and receive abdominal subcutaneous injection.
Duration of Tr
YKYY029 injection group(Cohort A):YKYY029 300mg
Dosage and Administration: Participants shall be assigned to corresponding dosage groups B and receive abdominal subcutaneous injection.
Duration of Tre
YKYY029 injection group(Cohort A):YKYY029 600mg
Dosage and Administration: Participants shall be assigned to corresponding dosage groups C and receive abdominal subcutaneous injection.
Duration of Tr
Placebo group(Cohort A):Placebo
Dosage and Administration: Appropriate volume, subcutaneous injection in the abdomen.
Duration of Treatment: 24weeks
YKYY029 injection group(Cohort B):YKYY029 injection 600mg
Dosage and Administration: Participants shall be assigned to corresponding dosage groups B and receive abdominal subcutaneous injection.
Dur
YKYY029 injection group(Cohort B):YKYY029 injection 300mg
Dosage and Administration: Participants shall be assigned to corresponding dosage groups C and receive abdominal subcutaneous injection.
Dura
Placebo group(Cohort B):Placebo
Dosage and Administration: Appropriate volume, subcutaneous injection in the abdomen.
Duration of Treatment: 24weeks
Sponsors
Peking University Third Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: Participants must meet all of the following criteria to be enrolled in the trial: 1. Male or female participants aged 18- 80 years (inclusive); 2. Male participants with body weight = 50.0 kg, female participants with body weight = 45.0 kg, and body mass index (BMI) of 19.0–35.0 kg/m² (inclusive); 3. At screening, participants must meet either of the following medication usage conditions, and have no plan to add any antihypertensive agents other than the study drug during the screening period and the entire treatment period: (1) Antihypertensive treatment naïve participants: defined as no use of any antihypertensive agents for at least 2 consecutive weeks prior to screening; (2) Participants receiving background antihypertensive treatment: defined as stable use of a maximum of 2 antihypertensive agents for at least 4 weeks prior to screening, with stable dose and agent type and no planned adjustment during the screening period and the entire double blind treatment period. Note: Permitted classes of antihypertensive agents include conventional therapies (ARB, ACEI, CCB, diuretics). Fixed-dose combinations shall be counted according to their components (e.g., Co Irbesartan Hydrochlorothiazide Tablets shall be counted as 2 antihypertensive agents). 4. Requirements for mean office sitting systolic blood pressure (SBP) during the screening period and prior to the first dose are as follows: regardless of background antihypertensive treatment, SBP must be within 140–169 mmHg (inclusive) for all participants; and all participants must have a mean daytime SBP = 135 mmHg by 24-hour ambulatory blood pressure monitoring (ABPM). 5. Maintained a normal diet for at least 4 weeks prior to screening, with no plan to significantly change diet or body weight during the study. 6. Agree to have no childbearing or fathering intention during the trial and within 12 months after the last dose, and voluntarily use effective contraceptive measures (including reliable methods judged by the investigator). 7. Able to understand trial requirements, voluntarily participate, and provide written informed consent.
Exclusion criteria
Exclusion criteria: Participants who meet any one or more of the following criteria are not eligible for the trial: 1. Severe hypertension (mean seated SBP = 180 mmHg and/or mean seated DBP = 110 mmHg); malignant hypertension, hypertensive emergency, hypertensive crisis, hypertensive encephalopathy, etc.; 2. History or diagnostic evidence of secondary hypertension, including but not limited to: renal parenchymal hypertension, renovascular hypertension (unilateral or bilateral renal artery stenosis), aortic coarctation, primary aldosteronism, Cushing’s syndrome, pheochromocytoma, polycystic kidney disease, drug-induced hypertension, etc.; 3. Use of any of the following medications within 4 weeks prior to randomization, or anticipated use during the study (other than investigational product): anti-anginal drugs (excluding trimetazidine and nicorandil), phosphodiesterase type 5 inhibitors (including sildenafil, tadalafil, vardenafil and avanafil), glucocorticoids (excluding topical or inhaled glucocorticoids), estrogens, licorice preparations, monoamine oxidase inhibitors, digitalis preparations, potassium supplements, and other chemical drugs, biological products, traditional Chinese medicines or natural products that, in the investigator’s opinion, are inappropriate or have significant effects on blood pressure. 4. Initiation, discontinuation, or other changes of sodium-glucose cotransporter 2 (SGLT2) inhibitor therapy within 4 weeks prior to screening. Patients who receive stable-dose SGLT2 inhibitor therapy for at least 4 weeks prior to screening and are expected to have no changes during study treatment may be enrolled. 5. Use of 3 or more antihypertensive agents concurrently (including 3 or more antihypertensive components in fixed-dose combinations) within 4 weeks prior to screening. 6. Type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus(Glycosylated hemoglobin, HbA1c = 8.0% at screening). 7. Any clinically significant abnormal findings on physical examination, vital signs, safety laboratory tests or other auxiliary examinations during the screening or baseline period, as judged by the investigator, or that participation would introduce unacceptable risk. Participants meeting any of the following laboratory criteria must be excluded: ALT, AST > 1.5 × upper limit of normal; Total bilirubin > 1.5 × upper limit of normal; Serum potassium > 5.5 mmol/L; Clinically significant abnormal thyroid function tests; eGFR < 30 mL/min/1.73m²; Positive result for any of the following tests: hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCVAb), treponema pallidum antibody (TPAb), human immunodeficiency virus antibody (HIV-Ab). 8. Heart rate < 50 beats/min or = 105 beats/min at screening and judged by the investigator to be clinically significant abnormalities . 9. History of orthostatic hypotension, or orthostatic hypotension at screening (symptomatic SBP reduction = 20 mmHg or DBP reduction = 10 mmHg upon standing). 10. History of syncope within 3 months prior to screening. 11. History of alcohol abuse within 6 months prior to screening. Alcohol abuse is defined as consumption of 14 alcohol units per week: 1 unit = 285 mL beer, 25 mL spirits, or 100 mL wine. 12. Patients with a confirmed diagnosis of anxiety or depression. 13. Major surgical procedure within 6 months prior to screening, or planned surgery during the study. 14. Known history of hypersensitivity to ARNI (e.g., sacubitril/valsartan), siRNA drugs, RAAS inhibitors (in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in mean office sitting systolic blood pressure (msSBP); | — |
Secondary
| Measure | Time frame |
|---|---|
| Change from baseline in 24 hour mean SBP and DBP as assessed by ambulatory blood pressure monitoring (ABPM);Change from baseline in mean office sitting diastolic blood pressure (msDBP);Mean office sitting blood pressure control rate (defined as the proportion of participants with sitting systolic blood pressure < 140 mmHg and sitting diastolic blood pressure < 90 mmHg);Change from baseline in msSBP and msDBP at each visit;Proportion of participants with a reduction from baseline in mean office sitting systolic blood pressure = 20 mmHg;Change from baseline in daytime and nighttime mean SBP and DBP as assessed by ABPM;To evaluate the percentage change in serum angiotensinogen (AGT) from baseline;Plasma PK parameters;Incidence of Anti-Drug Antibody(ADA)and Neutralizing Antibody(NAb);Adverse events (TEAE); | — |
Countries
China
Contacts
Public ContactRen Chuan,Tang Yida
Peking University Third Hospital
Outcome results
None listed