This is a single-center, open-label, exploratory clinical study designed to evaluate the safety and efficacy of a single-session injection of SC101, a small interfering RNA (siRNA) agent, into the perirenal fat. This study plans to enroll 3 participants, aged 18 to 65 years, who have a clinical diagnosis of resistant hypertension and moderate to severe chronic kidney disease (CKD).
Age ≥ 18 and ≤ 65 years.
Participants with an estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73m² and <40 mL/min/1.73m² during the screening period (eGFR is calculated using the Cockcroft-Gault equation).
Diagnosed with resistant hypertension: blood pressure (BP) remains uncontrolled after at least 4 weeks of treatment with at least 3 types of antihypertensive drugs (including one diuretic) at tolerated and sufficient doses, in addition to lifestyle modification. At the end of the screening and run-in period (baseline), resting office systolic BP (OSBP) ≥ 140 mmHg, resting office diastolic BP (ODBP) ≥ 90 mmHg, and 24-hour mean ambulatory systolic BP (MASBP) ≥ 130 mmHg.
Received stable doses of antihypertensive drugs for at least 4 weeks prior to screening, and can accept stable doses of antihypertensive drugs for 2 weeks during the run-in period.
Obvious pseudo-resistant hypertension caused by white-coat effect, incorrect BP measurement, poor medication adherence, use of drugs affecting antihypertensive efficacy, insufficient dosage, unreasonable combination therapy, or secondary hypertension (except obstructive sleep apnea) as judged by the investigator.
Confirmed history of secondary hypertension (including but not limited to renal artery stenosis, primary aldosteronism, pheochromocytoma, aortic coarctation, etc.).
Congenital renal abnormalities that may affect the safety and/or efficacy evaluation of the trial, including but not limited to solitary kidney or polycystic kidney disease.
Cardiovascular-related diseases that may affect safety evaluation, including but not limited to: uncontrolled symptomatic tachyarrhythmia or bradyarrhythmia (e.g., untreated persistent atrial fibrillation, second-degree or higher heart block, sick sinus syndrome); congestive heart failure NYHA Class III or IV; myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack within the past 6 months; severe structural heart disease (including moderate or higher valvular lesions, cardiomyopathy, congenital heart disease).
Single group
SC101
DrugA single-session bilateral injection of SC101 into the inferior perirenal fat under B-mode ultrasound guidance.
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Safety and tolerability assessments include AEs, SAEs, vital signs, physical exams, 12-lead electrocardiography, echocardiography, carotid and renal ultrasound, limb pulse wave velocity, and laboratory tests
Change from Baseline in 24-hour mean ambulatory blood pressure at Months 1, 2, 4, and 6
This includes changes in both 24-hour mean ambulatory systolic blood pressure (BP) and 24-hour mean ambulatory diastolic BP
Change from Baseline in Office Blood Pressure at Months 1, 2, 4, and 6
This includes changes in both Office Systolic Blood Pressure (OSBP) and Office Diastolic Blood Pressure (ODBP)
Response Rate of Office Blood Pressure Lowering at Months 1, 2, 4, and 6
"Response" is defined as achieving target BP (OSBP \< 140 mmHg and ODBP \< 90 mmHg) or a reduction from baseline of ≥ 10 mmHg in OSBP or ≥ 5 mmHg in ODBP
Percentage of Participants with a Reduction in the Number or Dosage of Baseline Antihypertensive Medications
Evaluation of the proportion of participants who successfully reduced their background medication while maintaining BP control
Exploratory Outcome: Change from Baseline in Renal Function Biomarkers at Months 1, 2, 4, and 6
This includes serum creatinine, blood urea nitrogen (BUN), serum cystatin C, serum uric acid, retinol binding protein, serum bicarbonate, electrolytes, estimated glomerular filtration rate (eGFR, calculated via Cockcroft-Gault equation), urinary albumin, urine total protein-to-creatinine ratio (UPCR), plasma renin and plasma Angiotensin II.
Exploratory Outcome: Systemic Exposure of SC101
This includes the plasma concentration of the SC101 siRNA agent to evaluate its systemic exposure following local injection into the perirenal fat
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The First Affiliated Hospital with Nanjing Medical University
Lead sponsor
Suzhou Municipal Hospital
Collaborator
