A Phase II Study of VB19055 in Uncontrolled or Resistant Hypertension

This study is a multicenter, randomized, double-blind, placebo parallel-controlled, dose-ranging Phase II clinical trial designed to evaluate the efficacy and safety of 12-week treatment with VB19055 in trial participants with hypertension (including resistant hypertension) whose blood pressure remains uncontrolled despite treatment with two or more antihypertensive medications, and to explore the dosing regimen for confirmatory studies.

Inclusion criteria

• Adult male and female aged ≥18 years;
• Mean seated systolic blood pressure (SBP) ≥140 mmHg and <170 mmHg at screening, and SBP ≥135 mmHg and <170 mmHg at randomization (Mean seated SBP/DBP is defined as the average of 3 seated SBP/DBP measurements obtained by automated office blood pressure measurement at a single clinic visit. If the trial participant has not taken routine antihypertensive medication prior to the visit, a repeat mean blood pressure measurement may be performed within 2 days after dosing.)
• Meet at least one of the following two criteria:

• Uncontrolled hypertension: At screening and randomization, as judged by the investigator, stably taking antihypertensive medications of two different therapeutic classes at maximum tolerated dose for ≥4 weeks (at least one must be a non-potassium-sparing diuretic). Beta-blockers used for other indications (e.g., migraine, heart failure, coronary artery disease) shall not count toward antihypertensive medications for eligibility;
• Resistant hypertension: At screening and randomization, as judged by the investigator, stably taking antihypertensive medications of ≥3 different therapeutic classes at maximum tolerated dose for ≥4 weeks (at least one must be a non-potassium-sparing diuretic). Beta-blockers used for other indications (e.g., migraine, heart failure, coronary artery disease) shall not count toward antihypertensive medications for eligibility.
• Serum potassium (K⁺) ≥3.5 and <5.0 mmol/L at screening (local laboratory);
• Morning (08:00 ± 2 hours) serum cortisol >3 µg/dL (local or central laboratory);
• Female participants of childbearing potential agree to no pregnancy plans and use highly effective contraception from ICF signing until 30 days after last dose; male participants agree to no fertility plans and use highly effective contraception from ICF signing until 90 days after last dose (see Appendix 2 for details);
• Voluntarily participate in this clinical study and have the capacity to sign the informed consent form.

Exclusion criteria

• Known causes of secondary hypertension: renal artery stenosis, uncontrolled or untreated hyperthyroidism/hypothyroidism, hyperparathyroidism, pheochromocytoma, Cushing's syndrome, aortic coarctation, or obstructive sleep apnea syndrome being treated with continuous positive airway pressure (CPAP) (participants with primary aldosteronism may be considered for enrollment unless adrenalectomy is planned before study completion);
• Have undergone coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or any major surgery (e.g., valve replacement, peripheral artery bypass surgery) within 6 months prior to ICF signing, or plan to undergo such procedures during the study;
• Arrhythmia requiring treatment or left bundle branch block at screening;
• Known chronic permanent atrial fibrillation;
• New York Heart Association (NYHA) Class III or IV chronic heart failure at screening;
• Glycated hemoglobin (HbA1c) >9.5% at screening;
• Adrenal insufficiency diagnosed within 6 months prior to ICF signing;
• Any of the following abnormal laboratory/physical examination findings at screening:

• Serum sodium <135 mmol/L;
• Mean seated SBP ≥170 mmHg or mean seated DBP ≥110 mmHg;
• Aspartate aminotransferase (AST) >3.0 × upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3.0 × ULN;
• Total bilirubin >2.0 × ULN, unless the participant has a history of Gilbert's syndrome;
• Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m²;
• Body mass index (BMI) <18 kg/m² or ≥45 kg/m²;
• Any of the following ECG abnormalities: heart rate <45 bpm or >110 bpm; QT interval corrected by Fridericia's formula (QTcF) >470 ms;
• Clinically significant abnormal chest imaging (chest X-ray or computed tomography [CT]) assessed by the investigator as posing a safety risk;
• Positive hepatitis B surface antigen (HBsAg) with possible viral replication (positive HBV DNA) as judged by the investigator based on further testing, or positive anti-hepatitis C virus (HCV) antibody, or positive human immunodeficiency virus (HIV) antibody.