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

• ClinicalTrials.gov Identifier: NCT05026866
• Recruitment Status: Recruiting
• First Posted: August 30, 2021
• Last Update Posted: May 17, 2023
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: August 27, 2021
• First Posted Date: August 30, 2021
• Last Update Posted Date: May 17, 2023
• Actual Study Start Date: August 27, 2021
• Estimated Primary Completion Date: October 25, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 27, 2021)

Time to clinical progression as measured by Clinical Dementia Rating - Global Score (CDR-GS) [ Time Frame: Estimated Up to Week 182 ]

Time to clinical progression as measured by CDR-GS. CDR is a clinician-rated scale that provides an overall assessment of the participant's stage on the spectrum of AD dementia.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 27, 2021)

• Change from Baseline in International Shopping List Test (ISLT) [ Time Frame: Baseline, Up to Week 182 ]
  Change from Baseline in clinical progression as measured by ISLT in participants with preclinical AD.
• Change from Baseline in Continuous Paired Associate Learning (CPAL) [ Time Frame: Baseline, Up to Week 182 ]
  Change from Baseline in clinical progression as measured by CPAL in participants with preclinical AD.
• Change from Baseline in International Daily Symbol Substitution Test-Medicines (iDSSTm) [ Time Frame: Baseline, Up to Week 182 ]
  Change from Baseline in clinical progression as measured by iDSSTm in participants with preclinical AD.
• Change from Baseline in Category Fluency [ Time Frame: Baseline, Up to Week 182 ]
  Change from Baseline in clinical progression as measured by Category Fluency in participants with preclinical AD.
• Change from Baseline in Face Name Association Test (FNAME) [ Time Frame: Baseline, Up to Week 182 ]
  Change from Baseline in clinical progression as measured by FNAME in participants with preclinical AD.
• Change from Baseline in Behavioral Pattern Separation-Object test (BPS-O) [ Time Frame: Baseline, Up to Week 182 ]
  Change from Baseline in clinical progression as measured by BPS-O in participants with preclinical AD.
• Change from Baseline in Cogstate Brief Battery (CBB) [ Time Frame: Baseline, Up to Week 182 ]
  Change from Baseline in clinical progression as measured by CBB in participants with preclinical AD.
• Change from Baseline in CDR-Sum of Boxes (CDR-SB) [ Time Frame: Baseline, Up Week 32 ]
  Change from Baseline in clinical progression as measured by CDR-SB in participants with preclinical AD.
• Change from Baseline in Cognitive Function Index (CFI) [ Time Frame: Baseline, Up to Week 182 ]
  Change from Baseline in clinical progression as measured by CFI in participants with preclinical AD.
• Change from Baseline in Montreal Cognitive Assessment (MoCA) score [ Time Frame: Baseline, Up to Week 182 ]
  Change from Baseline in clinical progression as measured by MoCA score in participants with preclinical AD.
• Pharmacokinetics (PK): Average Serum Donanemab Concentration at Steady State [ Time Frame: Baseline through Week 76 ]
  PK: Average Serum Donanemab Concentration at Steady State
• Percentage of Participants with Treatment-emergent Anti-Drug Antibody (ADAs) [ Time Frame: Baseline through Week 16 ]
  Percentage of Participants with Treatment-emergent Anti-Drug Antibody (ADAs)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Donanemab (LY3002813) Prevention Study in Participants With Alzheimer's Disease (TRAILBLAZER-ALZ 3)
• Official Title: A Study of Donanemab Versus Placebo in Participants at Risk for Cognitive and Functional Decline of Alzheimer's Disease
• Brief Summary: The main purpose of this study is to evaluate the safety and efficacy of donanemab in participants with preclinical Alzheimer's Disease (AD).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Alzheimer Disease

Intervention

• Drug: Donanemab
  Administered intravenously
  Other Name: LY3002813
• Drug: Placebo
  Administered intravenously

Study Arms

• Experimental: Donanemab
  Donanemab administered intravenously (IV)
  Intervention: Drug: Donanemab
• Placebo Comparator: Placebo
  Placebo is administered intravenously
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 27, 2021): 3300
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 8, 2027
• Estimated Primary Completion Date: October 25, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 and early-tau 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.

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 65 Years to 80 Years (Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or; 1-317-615-4559; ClinicalTrials.gov@lilly.com

• Listed Location Countries: Japan, Puerto Rico, United States

Administrative Information

• NCT Number: NCT05026866
• Other Study ID Numbers: 18284; I5T-MC-AACM ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: 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.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: http://vivli.org/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: May 2023