Perirenal SC101 injection to lower blood pressure in resistant hypertension with moderate–severe CKD

Safety and Efficacy of SC101 Via Perirenal Fat Injection for Resistant Hypertension in Patients With Moderate to Severe Chronic Kidney Disease

This trial will test whether a single injection of SC101 into the fat around the kidneys can lower blood pressure in adults with resistant hypertension and stage 3–4 chronic kidney disease.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 3 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: The First Affiliated Hospital with Nanjing Medical University (Academic / other)
• Locations: 1 site (Suzhou, Jiangsu)
• Trial ID: NCT07483372 on ClinicalTrials.gov

What this trial studies

This single-center, open-label, phase 1 proof-of-concept trial will deliver a single bilateral injection of SC101, an siRNA agent, into the perirenal adipose tissue of three adults with resistant hypertension and moderate-to-severe CKD. The primary focus is safety, with secondary measures tracking initial blood-pressure response and durability over follow-up. The protocol includes screening for resistant hypertension, confirmation of eGFR 15 to <40 mL/min/1.73 m2, and assessment of perirenal fat volume before bilateral injection. Investigators will also collect mechanistic data to explore the proposed perirenal fat–dorsal root ganglion axis as a contributor to hypertension.

Who should consider this trial

Good fit: Adults 18–65 years old with resistant hypertension uncontrolled despite at least three antihypertensive drug classes (including a diuretic) and an eGFR of 15 to <40 mL/min/1.73 m2 who have enough inferior perirenal fat for injection are the intended participants.

Not a fit: Patients with well-controlled blood pressure, eGFR ≥40 mL/min/1.73 m2 or <15 mL/min/1.73 m2, very little perirenal fat, or other exclusionary comorbidities are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, this approach could offer a localized, non-systemic option to lower blood pressure in people with resistant hypertension and moderate-to-severe CKD, potentially reducing medication needs and cardiovascular risk.

How similar studies have performed: This perirenal siRNA injection is a novel human application with limited direct precedent, although related renal-targeted interventions such as renal denervation have produced mixed results in prior trials.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 and ≤ 65 years.
* Participants with an estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73m\^2 and \<40 mL/min/1.73m\^2 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.
* The inferior perirenal fat volume is judged by the investigator to be sufficient for SC101 injection.
* Agreement to use effective contraceptive measures throughout the trial (within 1 year after SC101 injection), and women of childbearing potential must have a negative pregnancy test during the screening period.
* Capable of understanding and voluntarily signing the informed consent form, and able to complete the study in accordance with the protocol requirements.

Exclusion Criteria:

* 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).
* Abnormal liver function, defined as Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) \> 2 times the Upper Limit of Normal (ULN).
* Hematological diseases that may affect safety evaluation, including but not limited to anemia (Hemoglobin \< 90 g/L) or abnormal coagulation function (INR \> 1.5 or fibrinogen less than the lower limit of normal).
* Type 1 diabetes mellitus or poorly controlled hyperglycemia at screening (defined as HbA1c ≥ 7.5%).
* Urinary system diseases requiring surgical intervention at screening.
* Conditions unable to tolerate perirenal fat injection under local anesthesia, including but not limited to local skin problems or structural abnormalities adjacent to perirenal fat.
* Contraindications related to anesthetics (such as lidocaine).
* Life expectancy \< 1 year.
* History of malignant tumors (except those cured for more than 5 years without recurrence) or confirmed malignant tumors or precancerous lesions.
* Known Acquired Immunodeficiency Syndrome (AIDS) or HIV-positive status, or previous diagnosis of immunodeficiency with absolute neutrophil count \< 1000/mm\^3.
* Active liver disease participants, such as positive HAV antibody, positive HBV markers (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb, HBV DNA quantification), or positive HCV antibody (HCV Ab) and HCV RNA quantification above the detection limit.
* Positive Syphilis antibody and positive Rapid Plasma Reagin (RPR) test.
* Vaccination with live (attenuated) vaccines within 4 weeks before screening or planned during the trial.
* Currently participating in other clinical trials, or received other interventional clinical trial drugs within 3 months prior to enrollment.
* Currently using corticosteroids or immunosuppressants, where the investigator judges that dose adjustments will be required during the trial.
* Women who are breastfeeding.
* Other conditions that the investigator believes may affect compliance or make the participant unsuitable for the study.

Where this trial is running

Suzhou, Jiangsu

• Suzhou Municipal Hospital — Suzhou, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Xiangqing Kong, MD, PhD

Conditions Resistant Arterial Hypertension; Chronic Kidney Disease