Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MWX205

Официальное название

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered MWX205 Injection in Adult Participants With Dyslipidemia

Обзор

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?

Подробное описание

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.

Вмешательства

• Препарат MWX205
  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.
• Препарат Placebo
  Matching placebo

Первичные конечные точки

• Incidence of TEAEs [Срок оценки: From Day 1 to Day 86]
• Incidence of SAEs [Срок оценки: From Day 1 to Day 86]
• Number of participants with abnormal vital signs [Срок оценки: From Day 1 to Day 86]
• Number of participants with abnormal Physical examination findings [Срок оценки: From Day 1 to Day 337]
• Number of participants with abnormal ECG readings [Срок оценки: From Day 1 to Day 337]

Вторичные конечные точки (6)

• Plasma PK parameters Cmax (Maximum observed plasma drug concentration directly determined from the plasma concentration-time profiles) [Срок оценки: Day 1, Day 2, Day 3]
• Plasma PK parameters- Tmax (Time to maximum observed plasma drug concentration) [Срок оценки: Day 1, Day 2, Day 3]
• Plasma PK parameters- AUC0-inf (Area under the plasma concentration-time curve from time 0 extrapolated to infinity.) [Срок оценки: Day 1, Day 2, Day 3]
• Plasma PK parameters- AUC0-last (Area under the plasma concentration-time curve, from time zero to the last time point with measurable analyte concentration) [Срок оценки: Day 1, Day 2, Day 3]
• Urine PK parameters- Fe (dose fraction of the drug in its original form excreted in urine after administration) [Срок оценки: Day 1, Day 2, Day 3]
• Urine PK parameters- Ae (cumulative excretion of the drug's original form in urine) [Срок оценки: Day 1, Day 2, Day 3]

Критерии участия

Критерии включения

• Adult participants with dyslipidemia will be enrolled in this study.
• The absence of clinically significant illness and surgery within 4 weeks prior to study drug administration.
• 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.
• 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.
• 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

Критерии исключения

• Positive pregnancy test or lactating female participant.
• 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.
• QTcF over 450 ms at screening.
• 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%).
• 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%).
• 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.
• 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.
• Have received treatment with any liver-targeted siRNA therapy or ASO (Antisense Oligonucleotide) within12 months prior to screening.
• Use of ANGPTL3 or PCSK9-inhibiting monoclonal antibodies within 90 days prior to screening.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07634510 · MWX205-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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