Dyslipidemias
Conditions
Brief summary
This study is being done to test a new injection called MWX205 in people with high cholesterol or fat levels in the blood (dyslipidemia). Researchers will check if a single dose of MWX205 is safe and how the body reacts to it. They will also measure how quickly the drug enters the bloodstream and how long it stays in the body, and compare it with a placebo (inactive treatment). The study will help decide the right dose and understand how this medicine could be used in future treatments. The main questions this study aims to answer are: 1. Is MWX205 safe after a single dose? 2. How does the body process MWX205? 3. Does MWX205 show any effect on the body related to cholesterol levels?
Detailed description
This is a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose study in which the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of MWX205 Injection will be assessed in adult participants with dyslipidemia. Overall, 37 participants will be enrolled and assigned to 5 sequential cohorts (Cohorts 1 through 5). Cohort 1 will enroll 5 participants and be randomized 3:2 to receive a single dose of MWX205 or placebo (3 participants receiving MWX205 and 2 receiving a placebo). Cohorts 2 to 5 will be comprised of 8 participants per Cohort and randomized 3:1 to receive a single dose of MWX205 or placebo, respectively (6 participants receiving MWX205 Injection and 2 receiving a placebo). Dosing in each cohort will be such that 2 participants (1 MWX205 Injection and 1 placebo) will be administered at least 24 hours before the remaining 3 participants (the first cohort) or 6 participants (cohorts 2-5). After dosing the first 2 participants on a separate day, a minimum of a 5-minute dosing interval for the remaining 3 participants (the first cohort), or 6 participants (cohorts 2-5) in the following cohort, is considered acceptable. Continuation to dose the remaining 3 participants (Cohort 1) or 6 participants (Cohorts 2-5) will be at the investigator's discretion. Each participant will participate in 1 cohort only, residing at the Clinical Research Unit (CRU) from Day -1 (the day before dosing) to Day 8.
Interventions
DRUGMWX205
Each vial contains 200mg of MWX205 small nucleic acid, with water for injection as the solvent. The excipient, including sodium hydroxide and/or hydrochloric acid, may be added to adjust the pH to 6.5±0.2.
DRUGPlacebo
Matching placebo
Sponsors
Shanghai Minwei Biotechnology Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Adult participants with dyslipidemia will be enrolled in this study. 2. The absence of clinically significant illness and surgery within 4 weeks prior to study drug administration. 3. Participants must have fasting triglycerides greater than or equal to 150 mg/dL (1.7 mmol/L) and less than 500 mg/dL (5.7 mmol/L), and LDL-C greater than or equal to 70 mg/dL (1.8 mmol/L) at pre-screening and confirmation within 7 days before randomization. 4. Have a body mass index within the range 18.5 to 40.0 kg/m2 (inclusive), with no plans to significantly alter diet or BMI over the course of study. 5. Females of childbearing potential and males who are not surgically sterile (\> 90 days since vasectomy with no viable sperm) will agree to use contraception from Screening until 6 months after the administration, OR females of non-reproductive potential
Exclusion criteria
1. Positive pregnancy test or lactating female participant. 2. Systolic BP lower than 90 or over 140 mmHg, diastolic BP lower than 40 or over 90 mmHg, HR less than 40 or over 100 bpm at screening. 3. QTcF over 450 ms at screening. 4. Consume more than 7 units for women or 14 units for men of alcohol per week within 8 weeks prior to screening (1 unit = 285 mL of beer 3.5%, 75 mL of wine 13.5%, or 25 mL of distilled alcohol 40%). 5. Participants with established coronary artery disease, peripheral arterial disease, prior stroke, or other clinically significant atherosclerotic cardiovascular disease (such as stent placement or heart bypass, unstable angina or last known ejection fraction of \<50%). 6. History of intolerance to SC injection or relevant abdominal scarring (surgical, burns, etc.), or any skin conditions, including infections or open wounds, or dermatitis at the injection site that could interfere with the evaluation of injection reaction. 7. Have taken any prescription medications that are specifically indicated for lowering serum TGs (e.g., fibric acid derivatives, niacin, and omega-3 fatty acids \[\>1 g/day\]) or medications that interfere with absorption of dietary cholesterol or fats (e.g., bile acid sequestrants, orlistat) within 2 months prior to screening. 8. Have received treatment with any liver-targeted siRNA therapy or ASO (Antisense Oligonucleotide) within12 months prior to screening. 9. Use of ANGPTL3 or PCSK9-inhibiting monoclonal antibodies within 90 days prior to screening. 10. Use of systemic glucocorticoid therapy for more than 14 consecutive days in the past year, or any glucocorticoid therapy (excluding topical, intra-ocular, intra-articular, intranasal, or inhaled preparations) within 1 month before screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of TEAEs | From Day 1 to Day 86 | — |
| Incidence of SAEs | From Day 1 to Day 86 | — |
| Number of participants with abnormal vital signs | From Day 1 to Day 86 | Vital signs include tympanic body temperature, systolic and diastolic blood pressure, pulse rate, and respiratory rate |
| Number of participants with abnormal Physical examination findings | From Day 1 to Day 337 | Complete physical examinations include general appearance, mouth/dental (if required), neck (including thyroid \& nodes), cardiovascular, respiratory, gastrointestinal, renal, neurological, musculoskeletal, skin, other |
| Number of participants with abnormal ECG readings | From Day 1 to Day 337 | 12 Lead ECG: Triplicate readings to be taken within 2 to 5 minutes of each other. ECGs are to be taken after the participant has rested in the supine position for ≥ 5 minutes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma PK parameters Cmax (Maximum observed plasma drug concentration directly determined from the plasma concentration-time profiles) | Day 1, Day 2, Day 3 | Non-compartmental analysis (NCA) will be used to calculate the PK parameters with Phoenix WinNonlin Software |
| Plasma PK parameters- Tmax (Time to maximum observed plasma drug concentration) | Day 1, Day 2, Day 3 | Non-compartmental analysis (NCA) will be used to calculate the PK parameters with Phoenix WinNonlin Software |
| Plasma PK parameters- AUC0-inf (Area under the plasma concentration-time curve from time 0 extrapolated to infinity.) | Day 1, Day 2, Day 3 | Non-compartmental analysis (NCA) will be used to calculate the PK parameters with Phoenix WinNonlin Software |
| Plasma PK parameters- AUC0-last (Area under the plasma concentration-time curve, from time zero to the last time point with measurable analyte concentration) | Day 1, Day 2, Day 3 | Non-compartmental analysis (NCA) will be used to calculate the PK parameters with Phoenix WinNonlin Software |
| Urine PK parameters- Fe (dose fraction of the drug in its original form excreted in urine after administration) | Day 1, Day 2, Day 3 | Non-compartmental analysis (NCA) will be used to calculate the PK parameters with Phoenix WinNonlin Software |
| Urine PK parameters- Ae (cumulative excretion of the drug's original form in urine) | Day 1, Day 2, Day 3 | Non-compartmental analysis (NCA) will be used to calculate the PK parameters with Phoenix WinNonlin Software |
Contacts
CONTACTMohd Naguib bin Mohd Yunos, Dr.
PRINCIPAL_INVESTIGATORMohd Naguib bin Mohd Yunos, Dr.
Veritus Research
Outcome results
None listed