A Study of Donanemab (LY3002813) in Participants With Early Alzheimer's Disease (TRAILBLAZER-ALZ 2)

• ClinicalTrials.gov Identifier: NCT04437511
• Recruitment Status: Active, not recruiting
• First Posted: June 18, 2020
• Last Update Posted: February 14, 2023
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: June 17, 2020
• First Posted Date: June 18, 2020
• Last Update Posted Date: February 14, 2023
• Actual Study Start Date: June 19, 2020
• Estimated Primary Completion Date: April 14, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 3, 2021)

Change from Baseline on the integrated Alzheimer's Disease Rating Scale (iADRS) [ Time Frame: Baseline, Up to Week 76 ]

Change from Baseline on the iADRS in participants with early symptomatic AD in at least one of 'the low-medium tau pathology population or the overall population'.

Original Primary Outcome Measures (submitted: June 17, 2020)

Change from Baseline on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) [ Time Frame: Baseline, Week 76 ]

Change from Baseline on the CDR-SB

Current Secondary Outcome Measures (submitted: November 3, 2021)

• Change from Baseline on the Mini Mental State Examination (MMSE) Score [ Time Frame: Baseline, Up to Week 76 ]
  Change from Baseline on the MMSE Score in participants with early symptomatic AD in at least one of 'the low-medium tau pathology population or the overall population'.
• Change from Baseline on the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) [ Time Frame: Baseline, Up to Week 76 ]
  Change from Baseline on the ADAS-Cog13 in participants with early symptomatic AD in at least one of 'the low-medium tau pathology population or the overall population'
• Change from Baseline on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) [ Time Frame: Baseline, Up to Week 76 ]
  Change from Baseline on the CDR-SB in participants with early symptomatic AD in at least one of 'the low-medium tau pathology population or the overall population'.
• Change from Baseline on the Alzheimer's Disease Cooperative Study - instrumental Activities of Daily Living (ADCS-iADL) Score [ Time Frame: Baseline, Up to Week 76 ]
  Change from Baseline on the ADCS-iADL Score in participants with early symptomatic AD in at least one of 'the low-medium tau pathology population or the overall population'.
• Change from Baseline in Brain Amyloid Plaque Deposition as Measured by Florbetapir F18 Positron Emission Tomography (PET) Scan [ Time Frame: Baseline, Up to Week 76 ]
  Change from Baseline in Brain Amyloid Plaque Deposition as measured by Florbetapir F18 PET Scan
• Change from Baseline in Brain Tau Deposition as Measured by Flortaucipir F18 PET Scan [ Time Frame: Baseline, Up to Week 76 ]
  Change from Baseline in Brain Tau Deposition as Measured by Flortaucipir F18 PET Scan
• Change from Baseline in Brain Volume as Measured by volumetric Magnetic Resonance Imaging (vMRI) [ Time Frame: Baseline, Up to Week 76 ]
  Change from Baseline in Brain Volume as Measured by vMRI
• Pharmacokinetics (PK): Average Serum Concentration at Steady State of Donanemab [ Time Frame: Baseline through Week 76 ]
  PK: Average Serum Concentration at steady state of Donanemab
• Number or Participants with Anti-Donanemab Antibodies [ Time Frame: Baseline through Week 76 ]
  Number or Participants with Anti-Donanemab Antibodies

Original Secondary Outcome Measures (submitted: June 17, 2020)

• Change from Baseline on the Mini Mental State Examination (MMSE) Score [ Time Frame: Baseline, Week 76 ]
  Change from Baseline on the MMSE Score
• Change from Baseline on the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) [ Time Frame: Baseline, Week 76 ]
  Change from Baseline on the ADAS-Cog13
• Change from Baseline on the integrated Alzheimer's Disease Rating Scale (iADRS) [ Time Frame: Baseline, Week 76 ]
  Change from Baseline on the iADRS
• Change from Baseline on the Alzheimer's Disease Cooperative Study - instrumental Activities of Daily Living (ADCS-iADL) Score [ Time Frame: Baseline, Week 76 ]
  Change from Baseline on the Alzheimer's Disease Cooperative Study - instrumental Activities of Daily Living (ADCS-iADL) Score
• Change from Baseline in Brain Amyloid Plaque Deposition as Measured by Florbetapir F18 Positron Emission Tomography (PET) Scan [ Time Frame: Baseline, Week 76 ]
  Change from Baseline in Brain Amyloid Plaque Deposition as measured by Florbetapir F18 PET Scan
• Change from Baseline in Brain Tau Deposition as Measured by Flortaucipir F18 PET Scan [ Time Frame: Baseline, Week 76 ]
  Change from Baseline in Brain Tau Deposition as Measured by Flortaucipir F18 PET Scan
• Change from Baseline in Brain Volume as Measured by volumetric Magnetic Resonance Imaging (vMRI) [ Time Frame: Baseline, Week 76 ]
  Change from Baseline in Brain Volume as Measured by vMRI
• Pharmacokinetics (PK): Average Serum Concentration of Donanemab [ Time Frame: Baseline through Week 72 ]
  PK: Average Serum Concentration of Donanemab
• Number or Participants with Anti-Donanemab Antibodies [ Time Frame: Baseline through Week 76 ]
  Number or Participants with Anti-Donanemab Antibodies

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Donanemab (LY3002813) in Participants With Early Alzheimer's Disease (TRAILBLAZER-ALZ 2)
• Official Title: Assessment of Safety, Tolerability, and Efficacy of Donanemab in Early Symptomatic Alzheimer's Disease

Brief Summary

The reason for this study is to see how safe and effective the study drug donanemab is in participants with early Alzheimer's disease.

Additional participants will be enrolled to an addendum safety cohort. The participants will be administered open-label donanemab.

Detailed Description

TRAILBLAZER-ALZ 2 is a Phase 3, double-blind, placebo-controlled study to evaluate the safety and efficacy of N3pG antibody (donanemab) in participants with early symptomatic AD (prodromal AD and mild dementia due to AD) with the presence of brain tau pathology.

Following the double-blind 76-week main study period, a double-blind 78-week long-term extension period is added to further evaluate donanemab efficacy and safety over time. Participants from the addendum safety cohort are not eligible for the extension period.

• 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
  Given IV
  Other Name: LY3002813
• Drug: Placebo
  Given IV

Study Arms

• Experimental: Donanemab
  Donanemab given intravenously (IV).
  Intervention: Drug: Donanemab
• Placebo Comparator: Placebo
  Placebo given IV.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: November 3, 2021): 1800
• Original Estimated Enrollment (submitted: June 17, 2020): 500
• Estimated Study Completion Date: August 22, 2025
• Estimated Primary Completion Date: April 14, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Gradual and progressive change in memory function reported by participants or informants for ≥ 6 months
• MMSE score of 20 to 28 (inclusive) at baseline
• Meet 18F flortaucipir PET scan (central read) criteria - does not apply to safety cohort
• Meet 18F florbetapir PET scan (central read) criteria
• Have a study partner who will provide written informed consent to participate

Exclusion Criteria:

• Contraindication to MRI or PET scans
• Current treatment with immunoglobulin G (IgG) therapy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 60 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Czechia, Japan, Netherlands, Poland, Puerto Rico, United Kingdom, United States
• Removed Location Countries: France, Germany

Administrative Information

• NCT Number: NCT04437511
• Other Study ID Numbers: 17737; I5T-MC-AACI ( Other Identifier: Eli Lilly and Company ); 2020-000077-25 ( EudraCT Number )
• 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 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: February 2023