A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Dose Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of DD01 in Overweight/Obese Subjects With T2DM and NAFLD
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 255
- 试验地点
- 4
- 主要终点
- Heart Rate assessed by 24-hour ambulatory electrocardiography monitoring reader)
研究概览
简要总结
This is a Phase 1, first in human (FiH), randomized, double-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) study to investigate the safety, tolerability, PK and PD of DD01 administered by subcutaneous (SC) injection in overweight/obese subjects with type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD).
The study will be conducted in 2 Parts (Part A and B), with up to 8 cohorts included in each part (Part A; Cohorts A1 to A8 and Part B; Cohorts B2 to B8).
详细描述
Part A (SAD):
In Part A, subjects will receive a single dose of study drug, and the safety and efficacy of DD01 will be evaluated in overweight/obese subjects with T2DM.
Part B (MAD):
In Part B, subjects will receive once-weekly doses of the study drug for 4 weeks, and the safety and efficacy of DD01 will be evaluated in overweight/obese subjects with T2DM and NAFLD.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 2 diabetes ≥ 12 months.
- •Treatment with diet and exercise or metformin monotherapy on stable dose for 3 months prior to screening
- •HbA1c ≤ 10%).
- •Body Mass Index (BMI) ≥ 25 and ≤ 40.0 kg/m2
- •Part B Inclusion Criteria
- •Type 2 diabetes ≥ 12 months.
- •Treatment with diet and exercise or metformin monotherapy on stable dose for 3 months prior to screening
- •HbA1c ≤ 10%
- •BMI ≥ 30 kg/m2 and ≤ 40.0 kg/m2
- •Waist circumference ≤ 57 inches
- •Controlled attenuation parameter by FibroScan
- •Liver fat fraction ≥ 10% by magnetic resonance imaging (MRI)
排除标准
- •History of type 1 diabetes mellitus (T1DM)
- •History of acute proliferative retinopathy or maculopathy, severe gastroparesis, and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator.
- •Uncontrolled hypertension
- •Treatment with antihypertensive medication and statins not stable during the past 2 months prior to screening
- •Treatment with thyroid hormones not stable during the past 3 months prior to screening
- •History of any weight control treatment, including over-the-counter and herbal medication and supplements, or any medication with a labeled indication for weight loss or weight gain within 3 months prior to screening
- •History of surgical treatment for obesity
- •History of heart disease
- •History of renal disease
- •History or current diagnosis of acute or chronic pancreatitis or factors for pancreatitis, such as a history of cholelithiasis (without cholecystectomy) or alcohol abuse
- •A history of or active chronic liver disease due to alcohol, auto-immune, HIV, HBV or active HCV-infection or NASH
- •History of major depression, anxiety, suicidal behavior or attempts, or other psychiatric disorder requiring medical treatment
- •Personal or family history of medullary thyroid carcinoma (MTC) or a genetic condition that predispose to MTC (i.e., multiple endocrine neoplasia type 2)
- •Administration of Vaccines/Immunizations within 14 days prior to first dosing or if scheduled during the study. Vaccination for COVID-19 is allowed during the study if a washout period of 5 days after vaccine administration is followed before dosing.
- •History of any major surgery within 6 months prior to screening
- •Participation in any other clinical interventional study receiving active treatment within 30 days or 5 half-lives prior to screening, whichever is longer
- •History of alcohol or illicit drug abuse including marijuana
- •Existence of any surgical or medical condition that, in the judgment of the Investigator, might interfere with the investigational product
- •PART B Exclusion Criteria
- •History of type 1 diabetes mellitus (T1DM)
- •History of acute proliferative retinopathy or maculopathy, severe gastroparesis, and/or severe neuropathy, in particular autonomic neuropathy, as judged by the Investigator
- •Uncontrolled hypertension (treatment with medications must be stable)
- •History of any weight control treatment
- •History of surgical treatment for obesity
- •History of heart disease
- •History of renal disease
- •Subjects with a history or clinically significant active disease of the gastrointestinal, cardiovascular, hepatic, neurological, renal, pancreatic, immunological, dermatological, endocrine, genitourinary or hematological system.
- •History or current diagnosis of acute or chronic pancreatitis
- •History of major depression, anxiety, suicidal behavior or attempts, or other psychiatric disorder requiring medical treatment
- •History of alcohol or illicit drug abuse including marijuana
- •Existence of any surgical or medical condition that, in the judgment of the Investigator, might interfere with the investigational product
- •Any history of clinically significant chronic liver disease
研究组 & 干预措施
Group A2, Single Ascending Dose
DD01 Dose 2 (N=6) Placebo (N=2) Subcutaneous injection
干预措施: Placebo (Drug)
Group B2 - Multiple Ascending Dose
DD01 Dose 2 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
干预措施: Placebo (Drug)
Group A1 - Single Ascending Dose
DD01 Dose 1 (N=6) Placebo (N=2) Subcutaneous injection
干预措施: DD01 (Drug)
Group A1 - Single Ascending Dose
DD01 Dose 1 (N=6) Placebo (N=2) Subcutaneous injection
干预措施: Placebo (Drug)
Group A2, Single Ascending Dose
DD01 Dose 2 (N=6) Placebo (N=2) Subcutaneous injection
干预措施: DD01 (Drug)
Group A3, Single Ascending Dose
DD01 Dose 3 (N=6) Placebo (N=2) Subcutaneous injection
干预措施: DD01 (Drug)
Group A3, Single Ascending Dose
DD01 Dose 3 (N=6) Placebo (N=2) Subcutaneous injection
干预措施: Placebo (Drug)
Group A4, Single Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection
干预措施: DD01 (Drug)
Group A4, Single Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection
干预措施: Placebo (Drug)
Group B2 - Multiple Ascending Dose
DD01 Dose 2 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
干预措施: DD01 (Drug)
Group B3 - Multiple Ascending Dose
DD01 Dose 3 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
干预措施: DD01 (Drug)
Group B3 - Multiple Ascending Dose
DD01 Dose 3 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
干预措施: Placebo (Drug)
Group B4 - Multiple Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
干预措施: DD01 (Drug)
Group B4 - Multiple Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
干预措施: Placebo (Drug)
Group B5 - Multiple Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
干预措施: DD01 (Drug)
Group B5 - Multiple Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
干预措施: Placebo (Drug)
Group B6 - Multiple Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
干预措施: DD01 (Drug)
Group B6 - Multiple Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
干预措施: Placebo (Drug)
Group A5, Single Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection
干预措施: DD01 (Drug)
Group A5, Single Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection
干预措施: Placebo (Drug)
Group A6, Single Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection
干预措施: DD01 (Drug)
Group A6, Single Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection
干预措施: Placebo (Drug)
Group A7, Single Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection
干预措施: DD01 (Drug)
Group A7, Single Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection
干预措施: Placebo (Drug)
Group A8, Single Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection
干预措施: DD01 (Drug)
Group A8, Single Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection
干预措施: Placebo (Drug)
Group B7 - Multiple Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
干预措施: DD01 (Drug)
Group B7 - Multiple Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
干预措施: Placebo (Drug)
Group B8 - Multiple Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
干预措施: DD01 (Drug)
Group B8 - Multiple Ascending Dose
DD01 Dose 4 (N=6) Placebo (N=2) Subcutaneous injection once weekly for 4 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Heart Rate assessed by 24-hour ambulatory electrocardiography monitoring reader)
时间窗: Part B - 57 days
Number of participants with clinically significant abnormalities in 12-lead ECGs
时间窗: Part B - 57 days
Blood Pressure assessed by 24-hour ambulatory blood pressure monitoring (ABPM)
时间窗: Part B - 57 days
Number of participants with treatment-related adverse events and serious adverse events
时间窗: Part A - 43 days
Number of participants with clinically significant abnormalities in physical examinations
时间窗: Part B - 57 days
Number of participants with clinically significant abnormalities in vital signs
时间窗: Part B - 57 days
Number of participants with clinically significant abnormalities in clinical laboratory values
时间窗: Part B - 57 days
Number of participants with treatment-related adverse events and serious adverse events (TEAEs)
时间窗: Part B - 57 days
次要结局
- Maximum observed blood/plasma concentration of DD01(Part B - 57 days)
- Termination elimination rate constant of DD01(Part B - 57 days)
- Apparent total blood/plasma clearance of DD01(Part B - 57 days)
- Time of the maximum observed blood/plasma concentration of DD01(Part B - 57 days)
- Apparent blood/plasma terminal elimination half life of DD01(Part B - 57 days)
- Area under the blood/plasma concentration time curve from time zero to 216 hours postdose of DD01(Part B - 57 days)
- Area under the blood/plasma concentration time curve from time zero to 168 hours postdose of DD01(Part B - 57 days)
- Apparent volume of distribution of DD01(Part B - 57 days)
- Area under the blood/plasma concentration time curve from time zero to 144 hours postdose of DD01(Part B - 57 days)
- Area under the blood/plasma concentration time curve from time zero to the time of the last quantifiable concentration of DD01(Part B - 57 days)
- Number of participants with antidrug antibodies (ADAs)(Part B - 57 days)