A Donanemab (LY3002813) Study in Participants With Preclinical Alzheimer's Disease (TRAILBLAZER-ALZ 3)

Lilly

Status and phase: Active, not recruiting; Phase 3

Conditions: Alzheimer Disease

Treatments: Drug: Donanemab; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05026866

18284

I5T-MC-AACM (Other Identifier)

Details and patient eligibility

About

The main purpose of this study is to evaluate the safety and efficacy of donanemab in participants with preclinical Alzheimer's Disease (AD) over up to 332 weeks. Approximately 800 additional participants will be enrolled in the 12-month Addendum 7 to assess safety of a different titration regimen.

Enrollment: 2,996 estimated patients

Sex: All

Ages: 55 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• A Telephone Interview for Cognitive Status - modified (TICS-M) score reflective of intact cognitive functioning.
• Has a phosphorylated tau (P-tau) result consistent with the presence of amyloid pathology.
• Has a reliable study partner and backup study partner familiar with overall function and behavior, such as day-to-day activities and cognitive abilities.
• Have adequate literacy, vision, and hearing for neuropsychological testing at screening.
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
• Female participants include those who are infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation), congenital anomaly such as Mullerian agenesis; or post menopausal (women 55 or older not on hormone therapy and had at least 12 months of spontaneous amenorrhea; or with a diagnosis of menopause prior to starting hormone replacement therapy.

Treatment Extension: (Study Period II Placebo Group Only)

• Are actively participating in Study AACM at the conclusion of Study Period III.

Exclusion criteria

• Mild cognitive impairment or dementia, or significant other neurodegenerative disease that can affect cognition.
• Current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic, psychiatric, immunologic, or hematologic disease that could interfere with the analysis of the study or a life expectancy of approximately ≤5 years.
• History of cancer with high risk of recurrence and preventing completion of the trial.
• History of clinically significant multiple or severe drug allergies, or severe posttreatment hypersensitivity reactions (including but not limited to erythema multiforme major, linear immunoglobulin A dermatosis, toxic epidermal necrolysis, and/or exfoliative dermatitis).
• Have any clinically important abnormality at screening on magnetic resonance imaging (MRI) or clinical laboratory test results that could be detrimental to the participant or study integrity.
• Have any contraindications for MRI, including claustrophobia or the presence of contraindicated metal (ferromagnetic) implants/cardiac pacemaker.
• Have a centrally read MRI demonstrating presence of amyloid-related imaging abnormalities (ARIA-E), >4 cerebral microhemorrhages, more than 1 area of superficial siderosis, any macrohemorrhage or severe white matter disease at screening.
• Have had prior treatment with a passive anti-amyloid immunotherapy <5 half-lives prior to randomization.
• Have received active immunization against amyloid beta (Aβ) in any other study.
• Have received active immunization against Aβ in any other study.
• Current or previous use of prescription medications used as treatment for mild cognitive impairment (MCI) or AD.

Addendum 7 Exclusion Criteria:

• Same as the main study except contraindications for florbetapir F 18 PET are exclusionary.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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2,996 participants in 2 patient groups, including a placebo group

Donanemab

Experimental group

Description:

Donanemab administered intravenously (IV)

Treatment:

Drug: Donanemab

Placebo

Placebo Comparator group

Description:

Placebo is administered intravenously

Treatment:

Drug: Placebo