Alzheimer Disease
Conditions
Brief summary
The study involves repeated doses of LY3303560 given by infusion for 49 weeks. The study will examine how safe repeated doses of LY3303560 are, whether they cause side effects in participants with mild cognitive impairment or Alzheimer's Disease, and how LY3303560 is handled by the body and acts in the body. This study will last up to 65 weeks, not including screening. Screening is required within 90 days prior to the start of the study.
Interventions
DRUGLY3303560 - IV
Administered IV
DRUGPlacebo - IV
Administered IV
DRUGFlorbetapir F 18
Administered IV during the Positron Emission Tomography (PET) scan performed during screening.
DRUGFlortaucipir F18
Administered IV during the PET scan performed during the study.
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
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Mild Cognitive Impairment (MCI) due to Alzheimer's Disease (AD) or mild-to-moderate AD based on National Institute of Aging and Alzheimer's Association diagnostic criteria * Female participants: women not of child-bearing potential may participate, and include those who are: * Infertile due to surgical sterilisation (hysterectomy, bilateral oophorectomy, or for countries outside of Japan, tubal ligation), congenital anomaly such as mullerian agenesis; or * Postmenopausal defined as women at least 50 years of age with an intact uterus who have not taken hormones or oral contraceptives within 1 year, who have had either cessation of menses for at least 1 year, or 6 to 12 months of spontaneous amenorrhea with follicle-stimulating greater than (\>) 40 milli-international units per millilitre (mIU/mL) * Have a body weight of at least 50 kilogram (kg) (except for Japanese sites) and have a body mass index (BMI) of 18.0 to 35.0 kilogram per meter square (kg/m²) (for all sites), inclusive, at screening
Exclusion criteria
* Are currently enrolled in a clinical trial involving an investigational product (IP) or any other type of medical research judged not to be scientifically or medically compatible with this study * Have participated, within the last 30 days (3 months and 4 months for sites in the European Union \[EU\] and Japan, respectively) in a clinical trial involving an IP. If the previous IP has a long half-life, 3 months (4 months for sites in Japan) or 5 half-lives (whichever is longer) should have passed * Have known allergies to LY3303560, related compounds or any components of the formulation, or history of significant atopy * Have significant allergies to humanised monoclonal antibodies, diphenhydramine, adrenaline, or methylprednisolone; or have a history of clinically significant multiple or severe drug allergies, or intolerance to topical corticosteroids, or severe post treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A dermatosis, toxic epidermal necrolysis, or exfoliative dermatitis) * Have an increased risk of seizures as evidenced by a history of head trauma with loss of consciousness within the last 5 years or any seizure; prior electroencephalogram with epileptiform activity; surgery to the cerebral cortex; or history within the last 5 years of a serious infectious disease affecting the brain * Have any contraindications for Magnetic Resonance Imaging (MRI) studies, including claustrophobia, or the presence of metal (ferromagnetic) implants or a cardiac pacemaker * Have a history of intracranial haemorrhage, cerebrovascular aneurysm, or arteriovenous malformation, carotid artery occlusion, or epilepsy * Have received acetylcholinesterase inhibitors (AChEIs), memantine, and/or other AD therapy for less than 4 weeks, or have less than 4 weeks of stable therapy on these treatments by time of randomisation (including less than 4 weeks since stopping AChEIs and/or memantine); or have received medications that affect the central nervous system, except treatments for AD, for less than 4 weeks at a stable dose * Have used stable medical therapy for less than 2 months by time of randomization for any concurrent medical condition that is not exclusionary * Are currently using or intend to use drugs known to significantly prolong the QT interval, or who have a known risk factor for Torsades de Pointes. A participant will not be excluded if they have been using stable medication that is known to potentially cause significant prolongation of the QT interval, but does not present with any clinically significant prolongation of the QT interval at screening, in the opinion of the investigator * History of cancer within the last 5 years, with the exception of non-metastatic basal and/or squamous cell carcinoma of the skin, in situ cervical cancer, non-progressive prostate cancer, or other cancers with low risk of recurrence or spread.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | Baseline up to Week 65 | A summary of other non-serious adverse events (AEs), and all SAE's, regardless of causality, is located in the Reported Adverse Events section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3303560 at Week 49 | Week 49 (Pre-dose, 0.5, 2, 4, 8, 336, 672, 1344, 2016, 2688 hours post-dose) | PK Cmax at Week 49 |
| Pharmacokinetics: Area Under the Serum Concentration Time Curve During the Dosing Interval (AUC 0-tau) of LY3303560 | Week 49 (Pre-dose, 0.5, 2, 4, 8, 336, 672, 1344, 2016, 2688 hours post-dose) | PK: AUC 0-tau at Week 49. |
Countries
Japan, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo IV Placebo administered IV every 4 weeks for 25 weeks with the option of continuing treatment up to 49 weeks (up to g further doses), followed by a 16-week follow-up period. | 6 |
| 70 mg LY3303560 70 mg LY3303560 administered IV every 4 weeks for 25 weeks with the option of continuing treatment up to 49 weeks (up to g further doses), followed by a 16-week follow-up period. | 7 |
| 210 mg LY3303560 210 mg LY3303560 administered IV every 4 weeks for 25 weeks with the option of continuing treatment up to 49 weeks (up to g further doses), followed by a 16-week follow-up period. | 9 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo IV | 70 mg LY3303560 | 210 mg LY3303560 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 6 Participants | 8 Participants | 19 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 7 Participants | 9 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 6 Participants | 7 Participants | 17 Participants |
| Region of Enrollment Japan | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Region of Enrollment United Kingdom | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Region of Enrollment United States | 2 Participants | 6 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 4 Participants | 9 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 5 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 7 | 0 / 9 |
| other Total, other adverse events | 4 / 6 | 7 / 7 | 8 / 9 |
| serious Total, serious adverse events | 0 / 6 | 0 / 7 | 2 / 9 |
Outcome results
Primary
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
A summary of other non-serious adverse events (AEs), and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Time frame: Baseline up to Week 65
Population: All randomized participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo IV | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 70 mg LY3303560 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 210 mg LY3303560 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
Secondary
Pharmacokinetics: Area Under the Serum Concentration Time Curve During the Dosing Interval (AUC 0-tau) of LY3303560
PK: AUC 0-tau at Week 49.
Time frame: Week 49 (Pre-dose, 0.5, 2, 4, 8, 336, 672, 1344, 2016, 2688 hours post-dose)
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV | Pharmacokinetics: Area Under the Serum Concentration Time Curve During the Dosing Interval (AUC 0-tau) of LY3303560 | 9140 microgram*hour per milliliter (µg*hr/mL) | Geometric Coefficient of Variation 21 |
| 70 mg LY3303560 | Pharmacokinetics: Area Under the Serum Concentration Time Curve During the Dosing Interval (AUC 0-tau) of LY3303560 | 24200 microgram*hour per milliliter (µg*hr/mL) | Geometric Coefficient of Variation 19 |
Secondary
Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3303560 at Week 49
PK Cmax at Week 49
Time frame: Week 49 (Pre-dose, 0.5, 2, 4, 8, 336, 672, 1344, 2016, 2688 hours post-dose)
Population: All randomized participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo IV | Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3303560 at Week 49 | 29.2 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 23 |
| 70 mg LY3303560 | Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of LY3303560 at Week 49 | 83.9 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 22 |