A Single-Dose and Multiple-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LY3002813 in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease or Mild to Moderate Alzheimer's Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 63
- 试验地点
- 5
- 主要终点
- Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration
研究概览
简要总结
The study will evaluate the safety of LY3002813 by looking at adverse events. The study will also look at the effect the body has on LY3002813. Study participants will be healthy or will have mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or mild to moderate AD.
There will be seven groups of study participants. Five groups will receive a single dose of LY3002813 or placebo (no drug), followed by up to 4 multiple doses of LY3002813 or placebo given as an injection into a vein. Approximately 12 weeks will pass between the single dose and the first multiple dose. One group of participants will receive a single dose of LY3002813 given as an injection under the skin. One group of participants will receive a single dose of LY3002813 given as an injection into a vein.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy Participants:
- •Overtly healthy males, as determined by medical history and physical examination, willing to use a reliable method of birth control and will not donate sperm during the study
- •Between 18 to 40 years old.
- •Body Mass Index (BMI) of between 18.0 and 30.0 kilogram per meter square (kg/m^2), inclusive
- •Participants with Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or AD:
- •Present with mild cognitive impairment (MCI) due to AD or mild-to-moderate AD
- •Men or nonfertile women, at least 50 years of age. Nonfertile is defined as hysterectomy and/or bilateral oophorectomy, or amenorrhea for at least 1 year
- •Have a caregiver/study informant who provides a separate written informed consent to participate
- •Have adequate vision and hearing for neuropsychological testing in the opinion of the investigator
- •Positive florbetapir scan
排除标准
- •Healthy Participants: Have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, immunological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data
- •Participants with Mild Cognitive Impairment Due to AD or AD:
- •Do not have a reliable caregiver/study informant who is in frequent contact with the participant, who will accompany the participant to the office and/or be available by telephone at designated times, and will monitor administration of prescribed medications
- •Are being monitored for radiation due to occupational exposure to ionized radiation, or exposure to ionizing radiation within last 12 months from an investigational study
- •History within the past 5 years of a primary or recurrent malignant disease with the exception of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with a normal prostate-specific antigen post resection
- •All Participants:
- •History of intracranial hemorrhage, cerebrovascular aneurysm or arteriovenous malformation, or carotid artery occlusion, or stroke or epilepsy
- •Have any contraindications for magnetic resonance imaging (MRI) studies, including claustrophobia, the presence of contraindicated metal (ferromagnetic) implants, cardiac pacemaker
- •Have allergies to humanized monoclonal antibodies, including proteins and diphenhydramine, epinephrine, and methylprednisolone
- •Have gamma globulin therapy within the last year
- •Previously dosed in any other study investigating active immunization against amyloid beta (Aβ)
- •Previously dosed in any other study investigating passive immunization against Aβ within the last 6 months
研究组 & 干预措施
LY3002813-Single 0.1 mg/kg then multiple 0.3 mg/kg
0.1 milligram per kilogram (mg/kg) single dose then 0.3 mg/kg LY3002813 given every 4 weeks for up to 16 weeks intravenously (IV)
干预措施: LY3002813-IV (Biological)
LY3002813-Single then multiple 0.3 mg/kg
0.3 mg/kg single dose then 0.3 mg/kg LY3002813 given every 4 weeks for up to 16 weeks IV
干预措施: LY3002813-IV (Biological)
LY3002813-Single 1 mg/kg in Healthy Participants
1 mg/kg single dose LY3002813 given once by IV infusion.
干预措施: LY3002813-IV (Biological)
LY3002813-Single then multiple 1 mg/kg
1 mg/kg single dose then 1 mg/kg LY3002813 given every 4 weeks for up to 16 weeks IV
干预措施: LY3002813-IV (Biological)
LY3002813-Single then multiple 3 mg/kg
3 mg/kg single dose then 3 mg/kg LY3002813 given every 4 weeks for up to 16 weeks IV
干预措施: LY3002813-IV (Biological)
LY3002813-Single then multiple 10 mg/kg
10 mg/kg single dose then 10 mg/kg LY3002813 given every 4 weeks for up to 16 weeks IV
干预措施: LY3002813-IV (Biological)
Placebo-Single then multiple
Placebo given once, then every 4 weeks for up to 16 weeks IV
干预措施: Placebo-IV (Drug)
LY3002813-SC
Up to 3 mg/kg LY3002813 given once subcutaneously (SC)
干预措施: LY3002813-SC (Biological)
LY3002813-IV
Up to 3mg/kg LY3002813 given once intravenously (IV)
干预措施: LY3002813-IV (Biological)
结局指标
主要结局
Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration
时间窗: Day 1 up to Day 253
Data presented are the number of participants who experienced SAEs which were considered to be related to study treatment by the investigator while on treatment and during the follow-up. Summaries of SAEs and other non-serious adverse events (AEs), regardless of causality, are located in the Reported Adverse Events module.
次要结局
- Pharmacokinetics: Maximum Concentration (Cmax) of LY3002813(Pre-dose, end of infusion for IV or 1h post injection for SC, 3, 24, 72, 96(SC), 120(SC), 144(SC), 168, 336, 504, 672, 1008, 1344, 1680 and 2016 hours (h) post-dose)
- Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY3002813(Pre-dose, end of infusion for IV or 1h post injection for SC, 3, 24, 72, 96(SC), 120(SC), 144(SC), 168, 336, 504, 672, 1008, 1344, 1680 and 2016h post-dose)