Essential Hypertension, Healthy Volunteers
Conditions
Brief summary
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.
Interventions
DRUGMWX401 1
Administered subcutaneously (SC)
DRUGMWX401 2
Administered SC
DRUGMWX401 3
Administered SC
DRUGMWX401 4
Administered SC
DRUGMWX401 5
Administered SC
DRUGPlacebo
Administered SC
Sponsors
Shanghai Minwei Biotechnology Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of treatment-emergent adverse events (TEAEs) | Through study completion, for at least 85 days | Incidence and severity of TEAEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration (Cmax) | Up to 48 hours post-dose | Cmax of MWX401. |
| Time to Reach Maximum Concentration (Tmax) | Up to 48 hours post-dose | Tmax of MWX401. |
| Area Under the Curve From Time 0 to Last Quantifiable Time Point (AUC0-t) | Up to 48 hours post-dose | AUC0-t of MWX401. |
| Area Under the Curve From Time 0 to Infinity (AUC0-inf) | Up to 48 hours post-dose | AUC0-inf of MWX401. |
| Elimination Half-Life (t1/2) | Up to 48 hours post-dose | t1/2 of MWX401. |
| Cumulative Urinary Excretion (Ae) | Up to 72 hours post-dose | Ae of MWX401. |
| Cumulative Urinary Excretion from 0 to 48 hours (Ae0-48h) | Up to 72 hours post-dose | Ae0-48h of MWX401 |
| Fraction of Dose Excreted in Urine (Ae%) | Up to 72 hours post-dose | Ae% of MWX401. |
| Fractional Excretion (Fe) | Up to 72 hours post-dose | Fe of MWX401. |
| Renal Clearance (CLr) | Up to 72 hours post-dose | CLr of MWX401. |
| Change from Baseline in Serum Angiotensinogen (AGT) | Through study completion, for at least 85 days | Change value and percentage change from baseline in serum AGT. |
| Change from Baseline in Other RAAS Component Biomarkers | Through study completion, for at least 85 days | Change value and percentage change from baseline in other RAAS component (PRA, PRC, Ang I, Ang II, or ALD) biomarkers. |
| Change from Baseline in Blood Pressure | Through study completion, for at least 85 days | Change in systolic and diastolic blood pressure from baseline throughout the study. |
| Change from Baseline in 24-hour Ambulatory Blood Pressure | Up to Day 85 | Changes in mean systolic and mean diastolic blood pressure from baseline throughout the study. |
| Change from Baseline in Stroke Volume | Through study completion, for at least 85 days | Change from baseline in stroke volume. |
| Change from Baseline in Systemic Vascular Resistance | Through study completion, for at least 85 days | Change from baseline in systemic vascular resistance. |
| Detect anti-drug antibodies (ADA) | Through study completion, for at least 85 days | — |
Countries
China
Contacts
CONTACTWanxiang Chen
Outcome results
None listed