Alzheimer Disease
Conditions
Brief summary
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.
Interventions
BIOLOGICALLY3002813-IV
Administered IV
BIOLOGICALLY3002813-SC
Administered SC
DRUGPlacebo-IV
Administered IV
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
-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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Maximum Concentration (Cmax) of LY3002813 after the first dose was evaluated. |
| 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 | Area Under the Concentration Versus Time Curve From Time Zero to Infinity \[AUC(0-∞)\] of LY3002813 after the first dose was evaluated. |
Countries
Japan, United States
Participant flow
Pre-assignment details
Dose-escalation study in participants(pts) with mild cognitive impairment (MCI) due to Alzheimer's disease (AD).Under an amendment,Pharmacokinetics of unblinded single IV dose of 1 milligram per kilogram (mg/kg) LY3002813 in young,healthy male pts was assessed if absence of amyloid target affected the PK as compared to amyloid-positive pts with AD.
Participants by arm
| Arm | Count |
|---|---|
| Placebo IV Single dose of placebo matching LY3002813 given once, then every 4 weeks for up to 16 weeks by IV infusion. | 12 |
| 0.1 mg/kg / 0.3 mg/kg LY3002813 IV Single dose of 0.1 mg/kg LY3002813 given once, then 0.3 mg/kg LY3002813 every 4 weeks for up to 16 weeks by IV infusion. | 4 |
| 0.3 mg/kg LY3002813 IV Single dose of 0.3 mg/kg LY3002813 given once, then every 4 weeks for up to 16 weeks by IV infusion. | 7 |
| 1 mg/kg LY3002813 IV: Healthy Participants Single dose of 1 mg/kg LY3002813 given once by IV infusion. | 6 |
| 1 mg/kg LY3002813 IV Single dose of 1 mg/kg LY3002813 given once, then every 4 weeks for up to 16 weeks by IV infusion. | 9 |
| 3 mg/kg LY3002813 IV Single dose of 3 mg/kg LY3002813 given once, then every 4 weeks for up to 16 weeks by IV infusion. | 11 |
| 10 mg/kg LY3002813 IV Single dose of 10 mg/kg LY3002813 given once, then every 4 weeks for up to 16 weeks by IV infusion. | 6 |
| 3 mg/kg LY3002813 SC Single dose of 3 mg/kg LY3002813 given once SC. | 8 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Sponsor decision | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo IV | Total | 3 mg/kg LY3002813 SC | 10 mg/kg LY3002813 IV | 3 mg/kg LY3002813 IV | 1 mg/kg LY3002813 IV | 1 mg/kg LY3002813 IV: Healthy Participants | 0.3 mg/kg LY3002813 IV | 0.1 mg/kg / 0.3 mg/kg LY3002813 IV |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 76.8 years STANDARD_DEVIATION 4.9 | 69.7 years STANDARD_DEVIATION 16.4 | 74.5 years STANDARD_DEVIATION 9.5 | 72.3 years STANDARD_DEVIATION 10.7 | 73.0 years STANDARD_DEVIATION 8.8 | 74.7 years STANDARD_DEVIATION 9.3 | 25.8 years STANDARD_DEVIATION 3.3 | 75.0 years STANDARD_DEVIATION 8.4 | 71.3 years STANDARD_DEVIATION 11.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 59 Participants | 8 Participants | 5 Participants | 11 Participants | 8 Participants | 4 Participants | 7 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 21 Participants | 2 Participants | 2 Participants | 4 Participants | 3 Participants | 0 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 38 Participants | 6 Participants | 4 Participants | 6 Participants | 6 Participants | 5 Participants | 3 Participants | 2 Participants |
| Region of Enrollment Japan | 4 Participants | 20 Participants | 2 Participants | 2 Participants | 4 Participants | 3 Participants | 0 Participants | 3 Participants | 2 Participants |
| Region of Enrollment United States | 8 Participants | 43 Participants | 6 Participants | 4 Participants | 7 Participants | 6 Participants | 6 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Female | 7 Participants | 33 Participants | 5 Participants | 2 Participants | 8 Participants | 4 Participants | 0 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Male | 5 Participants | 30 Participants | 3 Participants | 4 Participants | 3 Participants | 5 Participants | 6 Participants | 3 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 12 | 3 / 4 | 4 / 7 | 3 / 6 | 6 / 9 | 7 / 11 | 2 / 6 | 4 / 8 |
| serious Total, serious adverse events | 1 / 12 | 0 / 4 | 2 / 7 | 0 / 6 | 1 / 9 | 0 / 11 | 0 / 6 | 0 / 8 |
Outcome results
Primary
Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration
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.
Time frame: Day 1 up to Day 253
Population: All enrolled participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo IV | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 1 Participants |
| 0.1 mg/kg / 0.3 mg/kg LY3002813 IV | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 0.3 mg/kg LY3002813 IV | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 2 Participants |
| 1 mg/kg LY3002813 IV: Healthy Participants | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 1 mg/kg LY3002813 IV | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 1 Participants |
| 3 mg/kg LY3002813 IV | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 10 mg/kg LY3002813 IV | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 3 mg/kg LY3002813 SC | Number of Participants With One or More Serious Adverse Events (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
Secondary
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY3002813
Area Under the Concentration Versus Time Curve From Time Zero to Infinity \[AUC(0-∞)\] of LY3002813 after the first dose was evaluated.
Time frame: 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
Population: All enrolled participants who received at least 1 dose of study drug and have evaluable pharmacokinetic data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY3002813 | 7.94 microgram*day per milliliter (μg*day/mL) | Geometric Coefficient of Variation 32 |
| 0.1 mg/kg / 0.3 mg/kg LY3002813 IV | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY3002813 | 26.3 microgram*day per milliliter (μg*day/mL) | Geometric Coefficient of Variation 33 |
| 0.3 mg/kg LY3002813 IV | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY3002813 | 91.6 microgram*day per milliliter (μg*day/mL) | Geometric Coefficient of Variation 17 |
| 1 mg/kg LY3002813 IV: Healthy Participants | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY3002813 | 79.9 microgram*day per milliliter (μg*day/mL) | Geometric Coefficient of Variation 26 |
| 1 mg/kg LY3002813 IV | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY3002813 | 263 microgram*day per milliliter (μg*day/mL) | Geometric Coefficient of Variation 19 |
| 3 mg/kg LY3002813 IV | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY3002813 | 1140 microgram*day per milliliter (μg*day/mL) | Geometric Coefficient of Variation 39 |
| 10 mg/kg LY3002813 IV | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY3002813 | 157 microgram*day per milliliter (μg*day/mL) | Geometric Coefficient of Variation 41 |
Secondary
Pharmacokinetics: Maximum Concentration (Cmax) of LY3002813
Maximum Concentration (Cmax) of LY3002813 after the first dose was evaluated.
Time frame: 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
Population: All enrolled participants who received at least 1 dose of study drug and have evaluable pharmacokinetic data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV | Pharmacokinetics: Maximum Concentration (Cmax) of LY3002813 | 2.90 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 35 |
| 0.1 mg/kg / 0.3 mg/kg LY3002813 IV | Pharmacokinetics: Maximum Concentration (Cmax) of LY3002813 | 5.99 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 77 |
| 0.3 mg/kg LY3002813 IV | Pharmacokinetics: Maximum Concentration (Cmax) of LY3002813 | 31.5 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 29 |
| 1 mg/kg LY3002813 IV: Healthy Participants | Pharmacokinetics: Maximum Concentration (Cmax) of LY3002813 | 21.7 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 21 |
| 1 mg/kg LY3002813 IV | Pharmacokinetics: Maximum Concentration (Cmax) of LY3002813 | 71.6 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 24 |
| 3 mg/kg LY3002813 IV | Pharmacokinetics: Maximum Concentration (Cmax) of LY3002813 | 218 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 16 |
| 10 mg/kg LY3002813 IV | Pharmacokinetics: Maximum Concentration (Cmax) of LY3002813 | 12.0 microgram per milliliter (μg/mL) | Geometric Coefficient of Variation 34 |