A Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Dose Escalation Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LAE102 Injection in Healthy and Overweight/Obese Subjects
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 160
- 试验地点
- 2
- 主要终点
- Number & severity of participants with treatment-related adverse events as assessed by CTCAE V5.0
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of LAE102 injection in healthy and overweight/obese participants, and also evaluate the preliminary pharmacodynamic effect of multiple dose injections in overweight/obese participants.
详细描述
Part A is a randomized, double-blinded, placebo-controlled, single ascending dose by Intravenous (IV) administration in 40 Healthy participants;
Part B is a randomized, double-blinded, placebo-controlled, single ascending dose by subcutaneous (SC) administration in 24 Healthy participants;
Part C is a randomized, double-blind, placebo-controlled, multiple dose ascending and expanding by subcutaneous (SC) administration in 60 overweight/obese participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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
- 是
入选标准
- •Male or female and aged 18 to 65 years (inclusive) at the screening visit
- •Male Body weight ≥ 50 kg, female Body weight ≥ 45 kg. For Part A&B, 18.5 ≤ BMI ≤ 28 kg/m². For part C, 26.0 ≤ BMI ≤ 40.0 kg/m²
- •Negative for human immunodeficiency virus antibody (HIV-Ab).
- •Female subjects with no childbearing potential or with childbearing potential which serum human chorionic gonadotropin (hCG) test must <5mIU/mL .
- •Male subjects are not allowed to donate sperm during this trial.
- •Voluntarily participate in the study and provide a signed and dated informed consent form.
- •Willing to comply with the scheduled visits, study treatment, laboratory tests, and other study-related procedures and requirements as stipulated in the study protocol.
排除标准
- •With clinically significant abnormalities in vital signs, physical examination, ECG or laboratory test results specified in the protocol.
- •Allergy to the investigational drug or its excipients, or a history of severe allergy (including any food or drug allergies).
- •Self-reported weight change is more than 5% in the previous 3 months prior to screening.
- •Diagnosed with secondary overweight or obesity.
- •Any clinically significant medical conditions and any diseases affecting the safety of the subject or the determination of study results.
- •History of major diseases or physical conditions in the central nervous system, respiratory system, cardiovascular system, digestive system, blood system, endocrine system, musculoskeletal diseases, mental illness, urinary system, or tumors, or any existing acute diseases, or other diseases or physical conditions that may affect the study or pose an unacceptable risk to the subjects.
- •Positive for hepatitis B surface antigen (HBsAg), or hepatitis C antibody (HCV-Ab), or syphilis spirochete antibody (TP-Ab).
- •Known or suspected history of substance abuse or positive drug screening test.
- •Alcohol abuse within 1 year before screening or positive alcohol breath test at baseline.
- •Smoking more than 5 cigarettes per day within 3 months before screening, or unable to comply with the prohibition of smoking during the study period.
- •Received any vaccine within 30 days prior to screening, or planned to receive any vaccine during the study period.
- •Inability to ensure no use of any drugs, including prescription and non-prescription drugs (excluding paracetamol, ibuprofen, and topically applied eye/nasal drops and ointments with no systemic exposure risk), vitamins, supplements and herbal medicines, from 14 days before the initial administration (if the half-life of the drug used exceeds 14 days, then 5 half-lives shall apply) until the last visit period.
- •Participated in any clinical trial and received an investigational medicine or medical device within 3 months prior to dosing of the investigational product.
- •Underwent major surgery within 30 days before the initial administration or planned to undergo major surgery during the study period.
- •Donated blood or experienced blood loss ≥400 mL within 3 months before screening or received a blood transfusion.
- •Have special dietary requirements and cannot comply with a standardized diet.
- •History of fainting or syncope.
- •Dieting or receiving weight loss treatment within 30 days before the initial administration or experiencing major changes in lifestyle.
- •Use of GLP-1 receptor agonists, or weight loss medications or systemic corticosteroids (oral or intravenous for more than 7 days), or psychiatric medications within 3 months prior to the initial administration. Applicable to part C.
- •Regular engaged in muscle strength related exercise, applicable to part C.
- •Other situation that the investigator considers not appropriate.
研究组 & 干预措施
Part A LAE102 IV
Single dose LAE102 by IV administration
干预措施: LAE102 intravenous administration (Drug)
Part A placebo IV
Single dose placebo by IV administration
干预措施: placebo intravenous administration (Drug)
Part B LAE102 SC
Single dose LAE102 by SC administration
干预措施: LAE102 subcutaneous administration (Drug)
Part B placebo SC
Single dose placebo by SC administration
干预措施: placebo subcutaneous administration (Drug)
Part C LAE102 SC
Multiple dose LAE102 by SC administration
干预措施: LAE102 multiple subcutaneous administration (Drug)
Part C placebo SC
Multiple dose placebo by SC administration
干预措施: Placebo multiple subcutaneous administration (Drug)
结局指标
主要结局
Number & severity of participants with treatment-related adverse events as assessed by CTCAE V5.0
时间窗: From Day 1 to Day 29 for single dose part. From Day 1 to Day 196 for multiple dose part
Findings on physical examination, ECG, vital signs, and reports of the laboratory results based on the CTCAE v5.0
次要结局
- characterize the peak of serum concentration (Cmax) of LAE102 injection in healthy subjects(From pre-dose to Day 29 for single dose part. From pre-dose to Day 196 for multiple dose part.)
- evaluate the expression levels of Activin A in blood samples(From pre-dose to Day 29 for single dose part. From pre-dose to Day 196 for multiple dose part.)
- characterize the area under the serum concentration versus time curve (AUC) of LAE102 injection in healthy subjects(From pre-dose to Day 29 for single dose part. From pre-dose to Day 196 for multiple dose part.)
- Incidence of positive Anti-drug antibody(ADA) after administration(pre-dose to Day 29 for single dose part. From pre-dose to Day 196 for multiple dose part.)