Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of LIB003 in Healthy Subjects With Hypercholesterolemia on Diet or Statin Therapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 63
- 试验地点
- 2
- 主要终点
- The incidence and severity of treatment emergent adverse events (TEAEs)
研究概览
简要总结
Randomized, double-blind, placebo-controlled, single ascending dose study in nine (9) separate and sequential dose cohorts (7 SC and 2 IV cohorts) to assess the safety and tolerability, pharmacokinetics and pharmacodynamics of LIB003 in subjects with moderately elevated LDL-C levels.
详细描述
After meeting eligibility criteria within each cohort subjects will be randomized to receive a single dose of LIB003. Seven (7) cohorts will receive LIB003 escalating doses of LIB003, or placebo, by SC injection and 2 cohorts LIB003 or placebo by IV infusion. Dose escalation will be based on the assessment of safety and tolerability data. All cohorts will each first enroll a sentinel group of subjects who will receive LIB003 or placebo in a double-blind fashion with the remaining subjects in that cohort only to be dosed after the safety data on day 4 from the sentinel subjects has been assessed and deemed safe.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
Within each dosing cohort randomization is performed according to a computer-generated randomization scheme. Other than the study drug prepared by an unblinded pharmacist and administered by unblinded nurses who will be instructed not to discuss randomized treatment assignments and have no other role in the study, all study staff and PI, along with the subjects are blinded as to treatment.
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
- 是
入选标准
- •* Men and women who are \>/=18 and \/=100 mg/dL who are either not on a lipid-lowering therapy or who are on stable statin therapy.
- •* Body mass index (BMI) \>18 and \<38 kg/m2
- •* Mild hypertensives on a stable dose of no more than one antihypertensive drug
排除标准
- •History of any prior or concomitant clinical condition or acute and/or unstable systemic disease compromising subject inclusion
- •Systolic blood pressure <90 mmHg or >160 mmHg or diastolic blood pressure <50 or >100 mmHg at screening
- •Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen, or hepatitis C virus antibody
- •Abnormal liver function test at Screening (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] >2 × the upper limit of normal [ULN]
- •Estimated glomerular filtration rate <60 mL/min/1.73 m2 at screening, as determined by the CKD-EPI Equation
- •History of prescription drug abuse, illicit drug use (including marijuana), or alcohol abuse
- •Unable to spend 4 days in confinement unit
- •History of allergy to protein-based biologics including, but not limited to, mAbs and vaccine
- •Any other finding which, in the opinion of the Investigator, would compromise the subject's safety or participation in the study
研究组 & 干预措施
cohort 8
LIB003 dose 3 SC - statin treated
干预措施: LIB003 (Biological)
cohort 6
LIB003 dose 4 IV
干预措施: LIB003 (Biological)
cohort 1
LIB003 dose 1 SC
干预措施: LIB003 (Biological)
cohort 2
LIB003 dose 2 SC
干预措施: LIB003 (Biological)
cohort 5
LIB003 dose 5 SC
干预措施: LIB003 (Biological)
cohort 9
LIB003 dose 4 SC - statin treated
干预措施: LIB003 (Biological)
cohort 7
LIB003 dose 5 IV
干预措施: LIB003 (Biological)
cohort 3
LIB003 dose 4 SC
干预措施: LIB003 (Biological)
cohort 4
LIB003 dose 4 SC
干预措施: LIB003 (Biological)
结局指标
主要结局
The incidence and severity of treatment emergent adverse events (TEAEs)
时间窗: 43 days
safety and tolerability will be assessed by the incidence and severity of treatment emergent adverse events
次要结局
- Absolute change in serum unbound (free) proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations over time(43 days)
- Absolute change in serum total PCSK9 over time(43 days)
- Percent change in Low Density Lipoprotein cholesterol (LDL-C) over time(43 days)
- Percent change in Apolipoprotein B (Apo B) over time(43 days)
- Changes in serum LIB003 concentrations over time(43 days)
- Presence of anti LIB003 antibodies (ADAs)(43 days)