Healthy Volunteers
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled, single ascending dose Phase 1 study designed to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of MWX203 Injection in healthy Chinese subjects. The study comprises six dose cohorts with a planned enrollment of 54 subjects. The primary endpoint is safety, assessed by adverse events (AEs), serious adverse events (SAEs), vital signs, physical examinations, laboratory tests, and 12-lead electrocardiograms. Secondary endpoints include plasma PK parameters, urinary PK parameters, and immunogenicity (anti-drug antibodies).
Interventions
DRUGMWX203 S1
administered subcutaneously (SC)
DRUGPlacebo
administered SC
DRUGMWX203 S2
administered SC.
DRUGMWX203 S3
administered SC.
DRUGMWX203 S4
administered SC.
DRUGMWX203 S5
administered SC.
DRUGMWX203 S6
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 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy male and female subjects aged 18 to 55 years (inclusive) at the time of signing the informed consent form (ICF). 2. Fasting serum LDL-C ≥ 2.6 mmol/L (100 mg/dL) and \< 4.1 mmol/L (158 mg/dL), and fasting triglycerides ≥ 1.1 mmol/L (100 mg/dL) and \< 5.7 mmol/L (500 mg/dL) at screening; no lipid-regulating drugs used within the past 3 months. 3. Body mass index (BMI) from 19.0 to 30.0 kg/m², inclusive, at screening; male subjects must have a body weight ≥ 50.0 kg and female subjects must have a body weight ≥ 45.0 kg. 4. Stable diet and physical-activity habits for 4 weeks prior to screening; no major changes to diet or exercise are planned during the study, and participants will not follow any weight-loss plan. 5. Subjects or their partners have no plans for pregnancy, sperm donation, or egg donation from the time of signing the ICF until at least 6 months after dosing, and agree to use medically-recognized, effective non-pharmacological contraceptive methods throughout the study. 6. Voluntarily participate in the study; able to read, understand, and sign the ICF before study participation; willing to comply with the study protocol and expected to complete the study.
Exclusion criteria
1. Any infectious disease within 4 weeks prior to screening (as judged by the investigator to affect the subject's ability to participate in the study). 2. Serious trauma or major surgery (requiring general anesthesia) within 6 months prior to screening, or planned major surgery during the study. 3. At screening, any of the following laboratory abnormalities: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), or total bilirubin \> 1.5 × ULN; serum creatinine \> 1.2 × ULN; or estimated glomerular filtration rate (eGFR) \< 90 mL/min/1.73 m² (calculated using the CKD-EPI equation, Appendix 4). 4. QTcF ≥ 450 ms (male) or ≥ 470 ms (female) at screening; or clinically-significant abnormalities on the 12-lead electrocardiogram. 5. HbA1c \> ULN. 6. Overall atherosclerotic cardiovascular disease (ASCVD) risk assessed by the investigator as moderate or high risk at screening. 7. Use of any liver-targeted oligonucleotide drug within 1 year prior to screening. 8. Pregnant or lactating female subjects at screening. 9. Difficult venous access, difficult subcutaneous injection, or intolerance to repeated venipuncture; or clinically significant needle phobia or blood phobia history as judged by the investigator. 10. Use of any over-the-counter medications, prescription medications, traditional Chinese medicine, vitamins, or health supplements within 2 weeks prior to screening or within 5 half-lives of any prior medication (whichever is longer). 11. Receipt of any live vaccine, live attenuated vaccine, or vaccines containing live viral components within 3 months prior to screening or planned vaccination during the study. 12. Any other condition judged by the investigator to make the subject unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events (AEs) | Through study completion, for at least 85 days | The incidence of adverse events (AEs) and serious adverse events (SAEs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Elimination Half-Life (t1/2) | Up to 48 hours post-dose | t1/2 of MWX203. |
| Terminal Elimination Rate Constant (λz) | Up to 48 hours post-dose | λz of MWX203. |
| Apparent Oral Clearance (CL/F) | Up to 48 hours post-dose] | CL/F of MWX203. |
| Apparent Volume of Distribution (Vd/F) | Up to 48 hours post-dose | Vd/F of MWX203. |
| Mean Residence Time (MRT) | Up to 48 hours post-dose | MRT of MWX203. |
| Cumulative Urinary Excretion (Ae) | Up to 48 hours post-dose | Ae of MWX203. |
| Fraction of Dose Excreted in Urine (Fe) | Up to 48 hours post-dose | Fe of MWX203. |
| Renal Clearance (CLr) | Up to 48 hours post-dose | CLr of MWX203. |
| Anti-Drug Antibody (ADA) | Up to Day 85 | ADA of MWX203. |
| Maximum Concentration (Cmax) | Up to 48 hours post-dose | Cmax of MWX203. |
| Time to Reach Maximum Concentration (Tmax) | Up to 48 hours post-dose | Tmax of MWX203. |
| Area Under the Curve From Time 0 to Infinity (AUC0-inf) | Up to 48 hours post-dose | AUC0-inf of MWX203. |
| Area Under the Curve From Time 0 to Last Quantifiable Time Point (AUC0-t) | Up to 48 hours post-dose | AUC0-t of MWX203. |
Countries
China
Outcome results
None listed