The reason for this study is to assess the safety and efficacy of donanemab in participants with early Alzheimer's disease. The study duration including screening and follow-up is up to 93 weeks.

TRAILBLAZER-ALZ 5 is a Phase 3, double-blind, placebo-controlled study to evaluate the safety and efficacy of donanemab in participants with early symptomatic AD (prodromal AD and mild dementia due to AD) and the presence of AD pathology.

Inclusion Criteria:

• Gradual and progressive change in memory function reported by the participant or informant for ≥6 months.

• A MMSE score of 20 to 28 (inclusive) at screening visit.

• Meet amyloid scan (central read) criteria.

• Have a study partner who will provide written informed consent to participate, is in frequent contact with the participant (defined as at least 10 hours per week), and will accompany the participant to the study or be available by telephone at designated times.

• A second study partner may serve as backup. The study partner(s) is/are required to accompany the participant for signing consent. The study partner must be present on all days the cognitive and functional scales are administered.

• If a participant has a second study partner, it is preferred that 1 study partner be primarily responsible for the CDR and the ADCS-ADL assessments.

• Days requiring the following assessments and scales must have a study partner available by telephone if not accompanying participant for the following assessments

  • AEs and concomitant medications
  • CDR, and
  • ADCS-ADL

• Stable concomitant symptomatic AD medications and other medications that may impact cognition for at least approximately 30 days prior to randomization.

Exclusion Criteria:

• Has significant neurological disease affecting the central nervous system other than AD, that may affect cognition or ability to complete the study, including but not limited to, other dementias, serious infection of the brain, Parkinson's disease, multiple concussions, or epilepsy or recurrent seizures (except febrile childhood seizures).
• Has current serious or unstable illnesses including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic (other than AD), psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the analyses in this study; or has a life expectancy of <24 months.
• History of cancer within the last 5 years, except of non-metastatic basal and/or squamous cell carcinoma of the skin, in situ cervical cancer, nonprogressive prostate cancer, or other cancers with low risk of recurrence or spread.
• Contraindication to MRI or PET scans.

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.