A Single- and Multiple-Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Intravenous Doses 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
- 61
- 试验地点
- 7
- 主要终点
- Change From Baseline in Florbetapir Positron Emission Tomography (PET) Scan Standard Uptake Value Ratio (SUVr)
研究概览
简要总结
The study will evaluate the effect of LY3002813 on brain scans. The study will evaluate the safety of LY3002813 by looking at adverse events (side effects). The study will also look at the effect the body has on LY3002813. Study participants will have mild cognitive impairment (MCI) due to AD or mild to moderate AD.
The study involves 3 parts.
- Part A in which participants will receive a single dose of LY3002813 or placebo (no drug).
- Part B in which participants will receive multiple doses of LY3002813 or placebo for 24 weeks.
- Part C in which participants will receive multiple doses of LY3002813 or placebo for up to 72 weeks.
Drug will be given as an intravenous infusion (injection into a vein). For Parts A, B and C, the study will last approximately 72 weeks, not including screening of approximately 56 days. The study is for research purposes only and is not intended to treat any medical condition.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Present with mild cognitive impairment (MCI) due to Alzheimer's disease (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 up to 2 partners who will provide 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
- •Do not have up to 2 reliable partners who are 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 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
- •Have current serious or unstable illnesses
研究组 & 干预措施
Part A: Placebo Single Dose (SD)
Participants received single intravenous (IV) dose of placebo.
干预措施: Placebo (Drug)
Part A: 10 Milligram Per Kilogram (mg/kg) LY3002813 SD
Participants received single IV dose of 10 mg/kg LY3002813.
干预措施: LY3002813 (Biological)
Part A: 20 mg/kg LY3002813 SD
Participants received single IV dose of 20 mg/kg LY3002813.
干预措施: LY3002813 (Biological)
Part A: 40 mg/kg LY3002813 SD
Participants received single IV dose of 40 mg/kg LY3002813.
干预措施: LY3002813 (Biological)
Part B: Placebo Q2W
Participants received multiple IV dose of placebo every 2 weeks (Q2W) for 24 weeks.
干预措施: Placebo (Drug)
Part B: 10 mg/kg LY3002813 Q2W
Participants received multiple IV dose of 10 mg/kg LY3002813 Q2W for 24 weeks.
干预措施: LY3002813 (Biological)
Part C: Placebo Q4W
Participants received multiple IV dose of placebo every 4 weeks (Q4W) for 72 weeks.
干预措施: Placebo (Drug)
Part C:10 mg/kg LY3002813 Q4W
Participants received multiple IV dose of 10 mg/kg LY3002813 Q4W for 72 weeks.
干预措施: LY3002813 (Biological)
Part C:20 mg/kg LY3002813 Q4W
Participants received multiple IV dose of 20 mg/kg LY3002813 Q4W for 72 weeks.
干预措施: LY3002813 (Biological)
结局指标
主要结局
Change From Baseline in Florbetapir Positron Emission Tomography (PET) Scan Standard Uptake Value Ratio (SUVr)
时间窗: Baseline, Week 72
Florbetapir PET imaging was used to confirm the presence of amyloid pathology consistent with AD. Change from baseline was done to test the hypothesis that amyloid burden was reduced in participants in the treatment group. The change from baseline to the postbaseline visit of the composite summary standard uptake value ratio of florbetapir F18 was calculated. Least square (LS) mean value was controlled for baseline value, baseline age, pooled investigator, treatment and visit. The composite summary measure is an unweighted average of the 6 smaller regions (anterior cingulate, frontal medial orbital, parietal, posterior cingulate, precuneus, and temporal) normalized to whole cerebellum or subject-specific white matter.
次要结局
- Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-tlast)] in Part A(Predose, end of infusion, 3, 24 and 48 hours postdose)
- Pharmacokinetics (PK): Area Under the Concentration Curve Versus Time at a Dosing Interval (AUCtau) at Day 1 of LY3002813 in Part B and Part C(Predose, end of infusion, 3, 24, 48 and 72 hours postdose)
- PK:Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of LY3002813 in Part B and C(Part B (Day 127): predose, end of infusion, 3, 24, 48 and 72 hours postdose; Part C (Day 141): predose, end of infusion, 3, 24, 48 and 72 hours postdose)
- PK: Maximum Serum Concentration (Cmax) of LY3002813 at Day 1 of LY3002813(Part A: Predose, end of infusion, 3, 24 and 48 hours postdose; Part B and C: Predose, end of infusion, 3, 24, 48 and 72 hours postdose)
- PK: Maximum Serum Concentration (Cmax) of LY3002813 at Steady State of LY3002813 in Part B and C(Part B (Day 127): predose, end of infusion, 3, 24, 48 and 72 hours postdose; Part C (Day 141): predose, end of infusion, 3, 24, 48 and 72 hours postdose)
- Percentage of Participants With Treatment-Emergent Anti-Drug Antibodies (TE-ADAs) to LY3002813(Predose up to Day 589)