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

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

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 Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Placebo; Biological: LY3002813

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Shinjuku-Ku, Japan, 169-0073
    • 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, 162-0053
    • 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.
  • Sumida-ku, Japan, 130-0004
    • 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.
• United States
  • Florida
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Orlando, Florida, United States, 32806
      • Compass Research
    • The Villages, Florida, United States, 32162
      • Compass Research
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • SNBL Clinical Pharmacology Center Inc
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • St. Louis Clinical Trials, LC
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • PRA Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Part A: Placebo Single Dose (SD); Participants received single intravenous (IV) dose of placebo.	Drug: Placebo; Administered IV
Experimental: Part A: 10 Milligram Per Kilogram (mg/kg) LY3002813 SD; Participants received single IV dose of 10 mg/kg LY3002813.	Biological: LY3002813; Administered IV
Experimental: Part A: 20 mg/kg LY3002813 SD; Participants received single IV dose of 20 mg/kg LY3002813.	Biological: LY3002813; Administered IV
Experimental: Part A: 40 mg/kg LY3002813 SD; Participants received single IV dose of 40 mg/kg LY3002813.	Biological: LY3002813; Administered IV
Placebo Comparator: Part B: Placebo Q2W; Participants received multiple IV dose of placebo every 2 weeks (Q2W) for 24 weeks.	Drug: Placebo; Administered IV
Experimental: Part B: 10 mg/kg LY3002813 Q2W; Participants received multiple IV dose of 10 mg/kg LY3002813 Q2W for 24 weeks.	Biological: LY3002813; Administered IV
Placebo Comparator: Part C: Placebo Q4W; Participants received multiple IV dose of placebo every 4 weeks (Q4W) for 72 weeks.	Drug: Placebo; Administered IV
Experimental: Part C:10 mg/kg LY3002813 Q4W; Participants received multiple IV dose of 10 mg/kg LY3002813 Q4W for 72 weeks.	Biological: LY3002813; Administered IV
Experimental: Part C:20 mg/kg LY3002813 Q4W; Participants received multiple IV dose of 20 mg/kg LY3002813 Q4W for 72 weeks.	Biological: LY3002813; Administered IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline, Week 72

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	Predose up to Day 589

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

• Click here for more information about this study: A Study of LY3002813 in Participants With Memory Damage Due to Alzheimer's Disease (AD)

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2015
• Primary Completion (Actual): August 28, 2019
• Study Completion (Actual): August 28, 2019

Study Registration Dates

• First Submitted: December 4, 2015
• First Submitted That Met QC Criteria: December 4, 2015
• First Posted (Estimated): December 8, 2015

Study Record Updates

• Last Update Posted (Actual): October 8, 2024
• Last Update Submitted That Met QC Criteria: July 8, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 16233; I5T-MC-AACD (Other Identifier: Eli Lilly and Company)