NCT07160257进行中（未招募）1 期
A Phase 1, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of Maridebart Cafraglutide on Insulin Sensitivity and β-cell Function in Participants With Type 2 Diabetes Mellitus
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Amgen
- 入组人数
- 56
- 试验地点
- 2
- 主要终点
- Change from Baseline in M-value from Hyperinsulinemic-euglycemic Clamp at Week 25
研究概览
简要总结
The primary objective of this study is to determine the effect of maridebart cafraglutide relative to placebo on insulin sensitivity in participants with Type 2 Diabetes Mellitus (T2DM) treated with stable dose of metformin.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent before initiation of any study-specific activities/procedures.
- •Male or female participants aged ≥ 18 and ≤ 70 years at the time of signing informed consent.
- •Body mass index ≥ 23.0 kg/m^2 (Asian participants only) or ≥ 25 and ≤ 45 kg/m^2 at screening.
- •Diagnosis of T2DM at least 6 months before screening based on the WHO classification.
- •Treatment of T2DM for at least 3 months prior to screening with diet and exercise and a stable dose of metformin (either immediate release or extended release), with or without a stable dose of 1 additional OAM other than metformin.
排除标准
- •Type 1 diabetes mellitus, history of ketoacidosis or hyperosmolar state/coma, or any other type of diabetes mellitus (except T2DM or history of gestational diabetes).
- •History of proliferative diabetic retinopathy or diabetic macular edema or nonproliferative diabetic retinopathy that requires acute treatment.
- •One or more episodes of severe hypoglycemia (Level 3 hypoglycemia as defined by the American Diabetes Association classification criteria) within 6 months before screening, as defined by the occurrence of neuroglycopenic symptoms requiring the assistance of another person for recovery.
- •Has modified diet or adopted any nutritional lifestyle modifications within 3 months prior to screening, as assessed by the investigator (or designee) based on participant self-report.
- •History of malignancy within the last 5 years before screening (except nonmelanoma skin cancers, cervical carcinoma in situ, or breast ductal carcinoma in situ).
- •Family (first-degree relative[s]) or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN-2).
- •History or evidence of endocrine disorder (such as Cushing's syndrome) that can cause obesity.
- •History or evidence of autoimmune disease that can directly or indirectly affect insulin production, insulin action, or glucose metabolism.
- •History of any of the following within 90 days before screening: myocardial infarction, unstable angina, coronary artery bypass graft surgery or other major cardiovascular surgery, percutaneous coronary intervention (diagnostic angiograms are permitted), transient ischemic attack, cerebrovascular accident, or decompensated congestive heart failure, or currently have New York Heart Association Class III or IV heart failure.
- •History of chronic pancreatitis.
- •History of acute pancreatitis within 6 months before screening.
- •Positive human immunodeficiency virus test at screening.
- •Evidence of hepatitis B or C infection.
- •Estimated glomerular filtration rate < 60 mL/min/1.73 m^2 calculated by the 2021 Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C equation at screening.
- •Hemoglobin value < 12 g/dL (males) or < 10 g/dL (females) at screening or check-in (Day -4).
- •Use within 90 days before randomization of medications, supplements, or alternative remedies for weight loss (eg, GLP-1RA, GIP agonists, phentermine/topiramate, naltrexone/bupropion, orlistat, and sympathomimetic drugs).
- •Use within 90 days before randomization of chronic (> 14 days) systemic glucocorticoid therapy (excluding topical, intraocular, intranasal, intraarticular, or inhaled preparations).
- •Use within 90 days before randomization of medications that may cause significant weight gain including, but not limited to, atypical antipsychotic and mood stabilizers.
- •Current or prior use of herbal supplements that affect insulin or glucose within 30 days before randomization.
- •Currently receiving treatment in another investigational device or drug study, or less than 30 days (or 5 half-lives, whichever is longer) since ending treatment on another investigational device or drug study(ies).
- •Participants of childbearing potential unwilling to adhere to contraception requirements during treatment and for an additional 16 weeks after the last dose of IMP.
- •Participants who are breastfeeding or who plan to breastfeed while on study through 16 weeks after the last dose of IMP.
- •Participants planning to become pregnant while on study through 16 weeks after the last dose of IMP.
- •Major surgical procedure planned during the study.
- •Participant has known sensitivity to any of the products or components to be administered during dosing.
- •Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participant and investigator's knowledge.
- •History or evidence of any other clinically significant disorder, condition, or disease (except for those outlined above) that, in the opinion of the investigator or medical monitor, if consulted as necessary, would pose a risk to participant's safety or interfere with the study evaluation, procedures, or completion.
研究组 & 干预措施
Placebo
Placebo Comparator
Participants will receive placebo SC.
干预措施: Placebo (Drug)
Maridebart cafraglutide
Experimental
Participants will receive maridebart cafraglutide subcutaneously (SC).
干预措施: Maridebart cafraglutide (Drug)
结局指标
主要结局
Change from Baseline in M-value from Hyperinsulinemic-euglycemic Clamp at Week 25
时间窗: Baseline and Week 25
次要结局
- Change from Baseline in Second Phase Insulin Secretion at Week 25(Baseline and Week 25)
- Change from Baseline in Fasting Triglycerides at Week 25(Baseline and Week 25)
- Change from Baseline in Fasting High-density Lipoprotein-cholesterol (HDL-C) at Week 25(Baseline and Week 25)
- Change from Baseline in Prospective Food Consumption Fasting Appetite VAS Score at Week 25(Baseline and Week 25)
- Change from Baseline in Overall Fasting Appetite VAS Score at Week 25(Baseline and Week 25)
- Change from Baseline in Overall Appetite VAS Score During sMMTT at Week 25(Baseline and Week 25)
- Change from Baseline in Food Craving Inventory (FCI) Score at Week 25(Baseline and Week 25)
- Change from Baseline in Caloric Intake During Ad Libitum Meal at Week 25(Baseline and Week 25)
- Change from Baseline in Body Fat Mass at Week 25(Baseline and Week 25)
- Number of Participants with Treatment-emergent Adverse Events and Serious Adverse Events(Up to Week 41)
- Plasma Concentration of Maridebart Cafraglutide at Week 25(Week 25)
- Number of Participants with Anti-maridebart Cafraglutide Antibody Formation(Up to Week 41)
- Change from Baseline in Total Insulin Secretion at Week 25(Baseline and Week 25)
- Change from Baseline in First Phase Incremental ISR from Hyperglycemic Clamp (ISR0-8min) at Week 25(Baseline and Week 25)
- Change from Baseline in Second Phase Insulin Secretion at Week 25(Baseline and Week 25)
- Change from Baseline in Maximum Insulin Secretion at 8 Minutes at Week 25(Baseline and Week 25)
- Change from Baseline in Maximum Insulin Secretion at 30 Minutes at Week 25(Baseline and Week 25)
- Change from Baseline in ISR at Week 25(Baseline and Week 25)
- Change from Baseline in Clamp Disposition Index (cDI) at Week 25(Baseline and Week 25)
- Change from Baseline in Post-meal Glucose Concentrations During sMMTT (Total and Incremental AUC0-240min) at Week 25(Baseline and Week 25)
- Change from Baseline in Hemoglobin A1c (HbA1c) at Week 25(Baseline and Week 25)
- Change from Baseline in Fasting Glucose Concentration at Week 25(Baseline and Week 25)
- Change from Baseline in Fasting Glucagon Concentration at Week 25(Baseline and Week 25)
- Change from Baseline in Glucagon Concentration During sMMTT (Total and Incremental AUC0-240min) at Week 25(Baseline and Week 25)
- Change from Baseline in Fasting Triglycerides at Week 25(Baseline and Week 25)
- Change from Baseline in Fasting High-density Lipoprotein-cholesterol (HDL-C) at Week 25(Baseline and Week 25)
- Change from Baseline in Fasting Non-HDL-C at Week 25(Baseline and Week 25)
- Change from Baseline in Triglyceride Concentration During sMMTT (Total and Incremental AUC0-240min) at Week 25(Baseline and Week 25)
- Change from Baseline in Fasting Free Fatty Acids (FFA) Concentration (During Hyperinsulinemic-euglycemic Clamp and sMMTT) at Week 25(Baseline and Week 25)
- Change from Baseline in Lean Body Mass at Week 25(Baseline and Week 25)
- Change from Baseline in Body Weight at Week 25(Baseline and Week 25)
- Change from Baseline in Waist Circumference at Week 25(Baseline and Week 25)
- Change from Baseline in Hunger Fasting Appetite Visual Analog Scale (VAS) Score at Week 25(Baseline and Week 25)
- Change from Baseline in Satiety Fasting Appetite VAS Score at Week 25(Baseline and Week 25)
- Change from Baseline in FFA Concentrations During sMMTT (Total AUC0-240min) at Week 25(Baseline and Week 25)
- Change from Baseline in Percentage Body Fat at Week 25(Baseline and Week 25)
- Change from Baseline in Fullness Fasting Appetite VAS Score at Week 25(Baseline and Week 25)
- Change from Baseline in Prospective Food Consumption Fasting Appetite VAS Score at Week 25(Baseline and Week 25)
- Change from Baseline in Overall Fasting Appetite VAS Score at Week 25(Baseline and Week 25)
- Change from Baseline in Hunger Appetite VAS Score During sMMTT at Week 25(Baseline and Week 25)
- Change from Baseline in Satiety Appetite VAS Score During sMMTT at Week 25(Baseline and Week 25)
- Change from Baseline in Fullness Appetite VAS Score During sMMTT at Week 25(Baseline and Week 25)
- Change from Baseline in Prospective Food Consumption Appetite VAS Score During sMMTT at Week 25(Baseline and Week 25)
- Change from Baseline in Overall Appetite VAS Score During sMMTT at Week 25(Baseline and Week 25)
- Change from Baseline in Food Craving Inventory (FCI) Score at Week 25(Baseline and Week 25)
- Change from Baseline in Caloric Intake During Ad Libitum Meal at Week 25(Baseline and Week 25)
研究者
研究点 (2)
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