Phase 1 Clinical Study of MWX401 Injection in Chinese Healthy Participants and Participants With Mild Hypertension

A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Subcutaneous Administration of MWX401 Injection in Chinese Healthy Participants and Participants With Mild Hypertension

This is a single-center, randomized, double-blind, placebo-controlled, single ascending-dose phase 1 clinical study, aimed at evaluating the safety, tolerability, PK, PD and immunogenicity of single subcutaneous administration of MWX401 Injection in healthy Chinese participants and participants with primary mild hypertension.

The study comprises five dose cohorts with a planned enrollment of 46 subjects. The primary endpoint is the incidence and severity of treatment-emergent adverse events. Secondary endpoints include plasma and urinary PK parameters, changes in serum AGT and RAAS components, changes in blood pressure and hemodynamics, and immunogenicity indicators.

Inclusion Criteria:

1. Male or female participants aged 18 to 60 years (inclusive) at the time of signing the informed consent form (ICF).
2. Body mass index (BMI) within 19.0 to 30.0 kg/m^2 (inclusive) at screening, with body weight >= 50 kg.
3. No use of antihypertensive medications within 30 days prior to signing the ICF, including beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), angiotensin receptor-neprilysin inhibitors (ARNIs), and diuretics.
4. At screening and baseline, average seated office blood pressure: healthy participants: SBP 120-139 mmHg (inclusive) and DBP 75-89 mmHg (inclusive); participants with mild hypertension: SBP 140-159 mmHg (inclusive) and DBP 90-99 mmHg (inclusive).

5.12-lead electrocardiogram results normal or judged by the investigator as abnormal without clinical significance, with QTcF (Fridericia's formula) < 450 ms (male) or < 470 ms (female).

6. Voluntarily sign the ICF before any study-related procedure, able to understand and willing to comply with the requirements of the study protocol.

Exclusion Criteria:

1. History or evidence of secondary hypertension, including renal parenchymal hypertension, renovascular hypertension, aortic stenosis, primary aldosteronism, Cushing's syndrome, pheochromocytoma, polycystic kidney disease, drug-induced hypertension, etc.
2. History of type 1 or type 2 diabetes mellitus.
3. Pulse/heart rate <55 bpm or >100 bpm at screening.
4. eGFR (CKD-EPI) <80 mL/min/1.73 m² at screening.
5. Body weight loss >5% within 6 months before screening, or planned weight loss during study.
6. History of or current orthostatic hypotension (SBP drop ≥20 mmHg or DBP drop ≥10 mmHg within 1 min of standing from supine).
7. History of syncope before screening.
8. Use of prescription drugs, herbal products, or dietary supplements that may affect safety or data integrity within 30 days before randomization.
9. Excessive blood pressure fluctuation (SBP fluctuation >20 mmHg during screening).
10. History of needle phobia, difficult blood sampling, or intolerance to venipuncture.
11. Any other condition deemed unsuitable for study by investigator.