A Study of LY3002813 in Participants With Memory Damage Due to Alzheimer's Disease (AD) or AD

Eli Lilly and Company61 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

Conditions

Alzheimer Disease

Interventions

Eligibility

Sex: ALLMin age: 50 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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

Locations (9)

Brain Matters Research

Delray Beach, Florida, United States

Compass Research

Orlando, Florida, United States

Compass Research

The Villages, Florida, United States

SNBL Clinical Pharmacology Center Inc

Baltimore, Maryland, United States

St. Louis Clinical Trials, LC

St Louis, Missouri, United States

PRA Health Sciences

Salt Lake City, Utah, United States

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Shinjuku-Ku, Japan

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.

Shinjuku-Ku, Japan

Sumida-ku, Japan

Outcomes

Primary Outcomes

Change From Baseline in Florbetapir Positron Emission Tomography (PET) Scan Standard Uptake Value Ratio (SUVr)

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.

Time frame: Baseline, Week 72

Secondary Outcomes

Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-tlast)] in Part A

Area under the curve from time zero to last quantifiable concentration \[AUC (0-tlast)\] at day 1 was reported.

Time frame: 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

Area under the concentration versus time curve during one dosing interval at day 1 was reported.

Time frame: 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

AUCtau of LY3002813 at steady state (Day 127 \[10 mg/kg Q2W\] for part B and Day 141 \[10 mg/kg and 20 mg/kg Q4W\]) for Part C following multiple dose administration of LY3002813 was evaluated.

Time frame: 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

Maximum serum concentration of LY3002813 during one dosing interval at day 1 was reported.

Time frame: 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

Cmax of LY3002813 at steady state (Day 127 \[10 mg/kg Q2W\] for part B and Day 141 \[10 mg/kg and 20 mg/kg Q4W\]) for Part C following multiple dose administration of LY3002813 was evaluated.

Time frame: 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

Blood samples were tested to determine if a participant reacted to LY3002813 by producing anti-LY3002813 antibodies. Samples were identified as TE-ADAs if the post-treatment sample had an increase of at least 4 fold in titer from pre-treatment values. If the pre-treatment value was not detected or was not present, a 1:20 post-treatment titer was required to indicate treatment emergence. The percentage of participants with TE ADA was calculated as: (the number of participants with TE ADA / total number of participants with at least 1 post-treatment immunogenicity sample analyzed)\*100.

Time frame: Predose up to Day 589