A Phase 1 Randomized, Blinded, Placebo-controlled Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Single-Ascending Doses of MEDI5884 in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 2
- 主要终点
- HDL-Cholesterol over time
研究概览
简要总结
A Phase 1, single dose study with 4 cohorts of ascending doses and an optional Japanese cohort designed to evaluate the safety, pharmacokinetics, and pharmacodynamics of MEDI5884 in healthy volunteers
详细描述
This is a first time in human, phase 1, randomized, blinded, placebo-controlled study to evaluate the safety, pharmacokinetics and pharmacodynamics of single ascending subcutaneous doses of MEDI5884 in healthy volunteers (age 18-55). The study consists of 4 cohorts of increasing doses (8 subjects each) and an optional Japanese American cohort (24 subjects) for a total of 56 healthy subjects. The decision whether or not to dose escalate will be based upon data review by the Dose Escalation Committee. Subjects will be randomized 3:1 to MEDI5884 or placebo. Following screening, the study consists of a 3 day inpatient stay and follow up visits. The number of follow up visits depend on the cohort assigned.
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy volunteers aged 18-55 years
- •Must provide written informed consent
- •Ability and willingness to adhere to the protocol
- •BMI 18-30kg/m2
- •Females not of childbearing potential
- •Males must practice 2 effective contraceptive measures if sexually active
- •Japanese descent for the Japanese cohort
排除标准
- •Any concurrent condition that in the opinion of the investigator would interfere with the evaluation of the investigational product
- •History or presence of gastrointestinal, renal, or hepatic disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
- •Abnormal lab values, physical exam, vital signs
- •Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks prior to dosing
- •Positive Hepatitis B, Hepatitis C or HIV test
- •Receipt of investigational therapy with 4 months from screening
- •Current or previous use of systemic corticosteroids 60 days prior to dosing or lipid lowering medications 28 days prior to dosing
- •Abnormal ECG
- •Recent plasma or blood donation
- •Positive drug or alcohol screen.
- •Current smoker
研究组 & 干预措施
MEDI5884 Dose 1
Participants will receive single dose of MEDI5884 Dose 1 injection SC on Day 1.
干预措施: MEDI5884 Dose 1 (Biological)
Placebo
Placebo will be administered subcutaneously (SC).
干预措施: Placebo (Biological)
MEDI5884 Dose 2
Participants will receive single dose of MEDI5884 Dose 2 injection SC on Day 1.
干预措施: MEDI5884 Dose 2 (Biological)
MEDI5884 Dose 3
Participants will receive single dose of MEDI5884 Dose 3 injection SC on Day 1.
干预措施: MEDI5884 Dose 3 (Biological)
MEDI5884 Dose 4
Participants will receive single dose of MEDI5884 Dose 4 injection SC on Day 1.
干预措施: MEDI5884 Dose 4 (Biological)
结局指标
主要结局
HDL-Cholesterol over time
时间窗: Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort.
HDL-Cholesterol over time
Number of subjects with adverse events as a measure of safety and tolerability of MEDI5884
时间窗: Baseline until last follow-up visit, assessed up to 90 days post dose depending on cohort.
Treatment emergent adverse events (TEAEs) and serious adverse events (TESAEs)
次要结局
- Lipoprotein particle number(Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing)
- Non-HDL-Cholesterol(Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing)
- Triglycerides(Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing)
- Lipoprotein particle size(Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing)
- Levels of total cholesterol(Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing)
- Very low-density lipoprotein cholesterol(Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing)
- Low-density lipoprotein cholesterol (direct and Friedewald equation)(Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing)
- Apolipoprotein A1(Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing)
- MEDI5884 serum concentration: maximum observed concentration(Post dose on Days 1, 2, 3, 7, 14, 21, 28, 45 (cohorts 2-4 and Japanese American), 60 (cohorts 3, 4 and Japanese American), 75 (cohort 4), and 90 (cohort 4))
- Apolipoprotein B(Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing)
- MEDI5884 serum concentration: time to maximum observed concentration(Post dose on Days 1, 2, 3, 7, 14, 21, 28, 45 (cohorts 2-4 and Japanese American), 60 (cohorts 3, 4 and Japanese American), 75 (cohort 4), and 90 (cohort 4))
- MEDI5884 serum concentration: area under the concentration time curve(Post dose on Days 1, 2, 3, 7, 14, 21, 28, 45 (cohorts 2-4 and Japanese American), 60 (cohorts 3, 4 and Japanese American), 75 (cohort 4), and 90 (cohort 4))
- MEDI5884 serum concentration: terminal half-life(Post dose on Days 1, 2, 3, 7, 14, 21, 28, 45 (cohorts 2-4 and Japanese American), 60 (cohorts 3, 4 and Japanese American), 75 (cohort 4), and 90 (cohort 4))
- Anti-drug antibody(Cohort 1: 28 days post dosing, Cohort 2: 45 days post dosing , Cohort 3: 60 days post dosing, Cohort 4: 90 days posting dosing, Optional Japanese American cohort: 60 days posting dosing)