A Study of LY4006895 in Healthy Participants With Early Symptomatic Alzheimer's Disease (AD)

Lilly

Status and phase: Enrolling; Phase 1

Conditions: Healthy; Alzheimer Disease

Treatments: Drug: Placebo; Drug: LY4006895

Study type: Interventional

Funder types: Industry

Identifiers

NCT06657768

27263

J5K-MC-OQAA (Other Identifier)

Details and patient eligibility

About

The main purpose of this study is to evaluate the safety and tolerability of the study drug known as LY4006895. Part A will administer a single-ascending dose in healthy participants or Part B will administer multiple-ascending doses in participants with early symptomatic Alzheimer's Disease (AD).

Blood tests will be performed to check how much LY4006895 gets into the bloodstream and how long it takes the body to eliminate it.

This is a 2-part study and will last approximately 29 weeks for Part A and 61 weeks for Part B, including a screening period for each part.

Enrollment: 128 estimated patients

Sex: All

Ages: 45 to 85 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria for Part A and Part B:

• Are overtly healthy as determined by medical evaluation. Rescreening is not allowed in this study
• Have a body mass index (BMI) within the range 18 to 40 kilogram per square meter (kg/m²)

For Part A:

• Have early symptomatic AD, as defined by:

  • Gradual and progressive change in memory function for at least 6 months, as reported by the participant or informant
  • A Mini-Mental State Exam (MMSE) score of 18 to 30 at screening
  • A Clinical Dementia Rating (CDR) global score of 0.5 to 1.0 (inclusive), with a memory box score greater than or equal to 0.5 at screening

For Part B:

• Have up to 2 reliable study partners who are in frequent contact with the participant (defined as at least 10 hours per week), one of whom at any one occasion: will accompany the participant to the study visits, will be available by telephone at designated times, and will provide a separate written informed consent to participate

Exclusion Criteria for Part A and Part B:

• Current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterological, respiratory, endocrinologic, neurologic (MAD: other than AD), psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the participant's ability to complete the study; or has a life expectancy of less than 24 months
• Have screening hemoglobin (Hb) less than 12 grams per deciliter (g/dL) or evidence of iron-deficiency (ferritin less than 30 nanograms per milliliter (ng/mL), or presence/history of hemoglobinopathy
• Are, in the judgment of the investigator, actively suicidal and therefore deemed to be at significant risk for suicide
• Regularly use known drugs of abuse and/or show positive findings on urinary drug screening that cannot be explained by regular concomitant medications
• Have previous exposure to any anti-tau therapy
• Are pregnant or intend to become pregnant or to breastfeed during the study

For Part B:

• Have a current exposure to an amyloid targeted therapy. Prior exposure to amyloid targeted therapies greater than 1 year from the last dose may be permitted at the discretion of the investigator and in consultation with the sponsor. A listing of amyloid targeted therapies will be provided
• Have a sensitivity to florataucipir 18F
• Have contraindication to magnetic resonance imaging (MRI) including claustrophobia or the presence of contraindicated metal (ferrogmagnetic) implants/cardiac pacemaker

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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128 participants in 4 patient groups, including a placebo group

LY4006895 of Part A (SAD)

Experimental group

Description:

Single-ascending doses of LY4006895 administered intravenously (IV)

Treatment:

Drug: LY4006895

Placebo Part A

Placebo Comparator group

Description:

Placebo administered IV

Treatment:

Drug: Placebo

LY4006895 of Part B (MAD)

Experimental group

Description:

Multiple-ascending doses of LY4006895 will be administered IV

Treatment:

Drug: LY4006895

Placebo Part B

Placebo Comparator group

Description:

Placebo administered IV

Treatment:

Drug: Placebo