A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetic Profile of MI226 Injection in Subjects With Abdominal Fat Accumulation
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Incidence and severity of treatment-emergent adverse events (TEAEs) as assessed by NCI CTCAE v6.0
研究概览
简要总结
This is a Phase 1, randomized, double-blind (with open-label sentinel cohorts), placebo-controlled, single-ascending-dose study designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of MI226 Injection in participants with abdominal fat accumulation.
详细描述
The study will enroll approximately 52 participants across 8 dose cohorts (24 mg to 1200 mg). The first two cohorts (24 mg and 60 mg) are open-label sentinel groups (2 participants each, all receiving active drug). Cohorts 3-8 are double-blind with a 6:1 or 8:1 randomization ratio to MI226 Injection or placebo. Each participant receives a single subcutaneous abdominal injection (0.2 mL per injection point, 1 cm apart, total volume up to 20 mL). The primary objectives are to assess the safety/tolerability and PK profile of MI226. Secondary objective is to evaluate the effect of MI226 on QT/QTc interval using a concentration-QTc (C-QTc) model in cohorts 5-8. Participants are followed for 28 days post-dose with serial safety assessments, PK blood sampling (13 time points over 24 hours for cohorts 3-8), and ECG monitoring. Dose escalation proceeds after review of 7-day safety data from the preceding cohort, with predefined stopping criteria.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged ≥18 and <65 years at the time of screening.
- •Male body weight ≥50 kg, female body weight ≥45 kg, and body mass index (BMI) between 19.0 kg/m² and 37.0 kg/m² (inclusive).
- •Presence of clinically appreciable abdominal fat accumulation, as assessed by the Clinical Photonumeric Rating Scale (CPnS) with a score of ≥2, and judged by the investigator as sufficient to accommodate the planned number of injections per assigned cohort.
- •Willingness to use effective contraceptive measures and to refrain from sperm/egg donation from the screening period until 3 months after the last dose of study drug; and no pregnancy plan during this period.
- •Ability to understand and voluntarily participate in the study, agree to comply with all study requirements, and provide written informed consent prior to any study-related procedures.
排除标准
- •Presence of any medical or physical condition that, in the judgment of the investigator, may interfere with the evaluation of efficacy or safety (e.g., uncontrolled hypertension, and respiratory, cardiovascular, hepatic, neurological, or thyroid diseases).
- •Presence of adipose tissue volume deficiency (e.g., post-traumatic) or immune-mediated lipodystrophy syndromes, including: generalized lipodystrophy (e.g., juvenile dermatomyositis-associated), partial lipodystrophy (e.g., Barraquer-Simons syndrome), or HIV-associated lipodystrophy.
- •History of or current clinically relevant skin disease that, in the judgment of the investigator, may affect the assessment of the injection site, or presence of keloid tendency (history of predisposition to hypertrophic scarring or keloid formation).
- •History of hypersensitivity (allergy to at least 2 substances) or known allergy to any component of the study drug.
- •Serious medical or psychiatric illness that, in the judgment of the investigator, may affect the study results or compromise participant compliance.
- •Restricted mobility, history of deep vein thrombosis or pulmonary embolism, or major surgery (within the past 3 months), or long-term hospitalization.
- •Known bleeding disorders, or use of medications that may increase the risk of post-injection bleeding (e.g., anticoagulant or antiplatelet therapy that cannot be safely discontinued) within 4 weeks prior to screening.
- •Females of childbearing potential who are pregnant, lactating, planning to become pregnant, or not using reliable contraceptive measures, and who are unwilling to use reliable contraception during the study (e.g., transdermal patches, intrauterine device/system [IUD/IUS], condoms, abstinence, or partner vasectomy).
- •Any other condition that, in the investigator's opinion, may significantly increase the participant's risk, confound the study results, or substantially interfere with the participant's participation in the study.
研究组 & 干预措施
MI226 Injection
干预措施: MI226 injection（dose 1） (Drug)
MI226 Injection
干预措施: MI226 Injection（dose 2） (Drug)
MI226 Injection
干预措施: MI226 Injection（dose 3） (Drug)
MI226 Injection
干预措施: MI226 injection（dose 4） (Drug)
MI226 Injection
干预措施: MI226 injection（dose 5） (Drug)
MI226 Injection
干预措施: MI226 Injection（dose 6） (Drug)
MI226 Injection
干预措施: MI226 Injection（dose 7） (Drug)
MI226 Injection
干预措施: MI226 injection（dose 8） (Drug)
placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence and severity of treatment-emergent adverse events (TEAEs) as assessed by NCI CTCAE v6.0
时间窗: Up to Day 28
Safety and tolerability will be evaluated by recording adverse events. AEs will be graded according to NCI CTCAE v6.0.
Number of participants with clinically significant abnormal physical examination findings
时间窗: Up to Day 28
Physical examination includes general appearance, skin, head and neck (eyes, ears, nose, throat), chest and lungs, cardiovascular system, abdomen, extremities, and neurological system. Clinically significant abnormalities will be recorded and summarized by system organ class.
Number of participants with clinically significant changes in vital signs
时间窗: Up to Day 28
Vital signs include systolic blood pressure (mmHg), diastolic blood pressure (mmHg), pulse rate (bpm), respiratory rate (breaths/min), and body temperature (°C). Clinically significant abnormalities in any of these parameters will be counted as an event.
Number of participants with clinically significant abnormal laboratory test results
时间窗: Up to Day 7
Laboratory examinations include hematology, serum chemistry, and urinalysis. Abnormalities will be graded according to CTCAE v6.0, and the number of participants with Grade ≥ 1 or clinically significant shifts from baseline will be summarized.
Number of participants with clinically significant abnormal 12-lead electrocardiogram (ECG) findings
时间窗: Up to Day 7
ECG parameters include heart rate (bpm), PR interval (msec), QRS duration (msec), and QT interval (msec). Clinically significant abnormalities will be recorded.
次要结局
- Maximum observed plasma concentration (Cmax) of MI226(From pre-dose to 24 hours post-dose)
- Time to reach maximum observed plasma concentration (Tmax) of MI226(From pre-dose to 24 hours post-dose)
- Terminal elimination half-life (t1/2) of MI226(From pre-dose to 24 hours post-dose)
- Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) of MI226(From pre-dose to 24 hours post-dose)