A Follow-On Study of Donanemab (LY3002813) With Video Assessments in Participants With Alzheimer's Disease (TRAILBLAZER-EXT)

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04640077
Collaborator
(none)
90
28
2
39.4
3.2
0.1

Study Details

Study Description

Brief Summary

The main goals of this study are to further determine whether the study drug donanemab is safe and effective in participants with Alzheimer's disease and to validate video scale assessments.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
90 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Donanemab Follow-On Study: Safety, Tolerability, And Efficacy in Symptomatic Alzheimer's Disease With Validation of Remote Neuropsychological Assessments
Actual Study Start Date :
Nov 23, 2020
Anticipated Primary Completion Date :
Sep 19, 2023
Anticipated Study Completion Date :
Mar 5, 2024

Arms and Interventions

Arm Intervention/Treatment
Other: Part A Validation of Remote Scale Assessments

Alternating at-home and on-site cognitive and functional scale assessments Group 1: Cognitive/functional scale assessment at the study site (on-site), followed by an at-home assessment (VTC; video teleconference), or Group 2: Cognitive/functional scale assessment at home (VTC), followed by assessment on-site

Other: No Intervention
No intervention

Other: Part B Donanemab

Donanemab administered intravenously (IV)

Drug: donanemab
Administered IV
Other Names:
  • LY3002813
  • Outcome Measures

    Primary Outcome Measures

    1. Part A: Correlation between VTC and on-site assessment for PAIR 1 for Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) [1 Month]

      Correlation between VTC and on-site assessment for PAIR 1 (defined as completing a VTC evaluation and one in person evaluation regardless of order) for the ADAS-Cog13. The ADAS-Cog13 (13-item version of ADAS Cog) assesses areas of cognitive function that are the most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation, and maze-completion measures. The ADAS-Cog13 scale ranges from 0 to 85, with higher scores indicating greater disease severity.

    2. Part A: Correlation between VTC and on-site assessment for PAIR 1 for Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) [1 Month]

      Correlation between VTC and on-site assessment for PAIR 1 for ADCS-ADL. The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The range for the total ADCS-ADL score is 0 to 78, with lower scores indicating greater level of impairment. Alzheimer's Disease Cooperative Study Instrumental Activities of Daily Living Inventory (ADCS-iADL) is calculated from a subset of questions from the ADCS-ADL. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance.

    3. Part A: Correlation between VTC and on-site assessment for PAIR 1 for Mini Mental State Examination (MMSE) Score [1 Month]

      Correlation between VTC and on-site assessment for PAIR 1 for MMSE. The MMSE is a brief instrument used to assess cognitive function in participants. The range for the total MMSE score is 0 to 30, with lower scores indicating greater level of impairment.

    4. Part A: Correlation between VTC and on-site assessment for PAIR 1 for Clinical Dementia Rating-Sum of Boxes (CDR-SB) [1 Month]

      Correlation between VTC and on-site assessment for PAIR 1 for CDR-SB. The CDR-SB is a global assessment tool than can be used to effectively evaluate both cognition and function. The CDR-SB scores are calculated by adding the box scores and range from 0 to 18 (with higher scores indicative of more impairment).

    5. Part B: Percentage of Participants with One or More Adverse Events (AEs) or Serious AEs [Up to 72 Weeks]

      A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

    Secondary Outcome Measures

    1. Part B: Change from Baseline on the MMSE Score [Baseline, Week 72]

      Change from Baseline on the MMSE Score. The MMSE is a brief instrument used to assess cognitive function in participants. The range for the total MMSE score is 0 to 30, with lower scores indicating greater level of impairment.

    2. Part B: Change from Baseline on the ADAS-Cog13 score [Baseline, Week 72]

      Change from Baseline on the ADAS-Cog13. The ADAS-Cog13 (13-item version of ADAS Cog) assesses areas of cognitive function that are the most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation, and maze-completion measures. The ADAS-Cog13 scale ranges from 0 to 85, with higher scores indicating greater disease severity.

    3. Part B: Change from Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) [Baseline, Week 72]

      Change from Baseline on the iADRS. The iADRS is a composite that measures both cognition and function from the ADAS- Cog and the ADCS-iADL. The iADRS is calculated as a linear combination of the total scores of the ADAS-Cog13 (score range 0 to 85 with higher scores reflecting worse performance) and the ADCS-iADL (score range from 0-59 with higher scores reflecting better performance). The iADRS score ranges from 0 to 144 with lower scores indicating greater impairment.

    4. Part B: Change from Baseline on the ADCS-iADL [Baseline, Week 72]

      Change from Baseline on the ADCS-iADL. The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The range for the total ADCS-ADL score is 0 to 78, with lower scores indicating greater level of impairment. ADCS-iADL is calculated from a subset of questions from the ADCS-ADL. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance.

    5. Part B: Change from Baseline on the CDR-SB [Baseline, Week 72]

      Change from Baseline on the CDR-SB. The CDR-SB is a global assessment tool than can be used to effectively evaluate both cognition and function. The CDR-SB scores are calculated by adding the box scores and range from 0 to 18 (with higher scores indicative of more impairment).

    6. Part B: Change from Baseline in Brain Amyloid Plaque Deposition as Measured by Florbetapir F18 Positron Emission Tomography (PET) Scan [Baseline, Week 72]

      Change from Baseline in Brain Amyloid Plaque Deposition as Measured by Florbetapir F18 PET Scan

    7. Part B: Change from Baseline in Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI) measures [Baseline, Week 72]

      Change from Baseline in Brain Volume as Measured by vMRI

    8. Part B: Pharmacokinetics (PK): Average Serum Concentration of Donanemab [Predose, Up to Week 72]

      PK: Average Serum Concentration of donanemab

    9. Part B: Number or Participants with Anti-Donanemab Antibodies [Baseline to Week 72]

      Number or Participants with Anti-donanemab Antibodies

    10. Part B: Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) [Baseline, Week 72]

      Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS). The C-SSRS is a scale that captures the occurrence, severity, and frequency of suicidal ideation and behavior during the assessment period via a questionnaire. Some questions are yes/no and some are on a scale of 1 (low severity) to 5 (high severity).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    60 Years to 90 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Participated in a double-blind treatment period of a sponsor-approved originating donanemab trial, for example the TRAILBLAZER-ALZ study.

    • Have a study partner

    • Stable symptomatic Alzheimer's Disease (AD) medications and other medication that may impact cognition for at least 30 days prior to randomization into Part A

    Exclusion Criteria:
    • 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 outcome assessments or the analyses in this study.

    • Have received treatment with a passive anti-amyloid immunotherapy after completion of originating donanemab study or received active immunization against Aβ in any other study.

    • Poor venous access

    • Contraindication to PET or MRI imaging

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Banner Alzheimer's Institute Phoenix Arizona United States 85006
    2 Irvine Clinical Research Irvine California United States 92614
    3 UC Irvine-Institute for Memory Impairments and Neurological Disorders (UCI MIND) Irvine California United States 92697
    4 Bradenton Research Center, Inc. Bradenton Florida United States 34205
    5 Merritt Island Medical Research, LLC Merritt Island Florida United States 32952
    6 Synexus Clinical Research US, Inc - Orlando Orlando Florida United States 32806
    7 Advanced Research Consultants Palm Beach Gardens Florida United States 33410
    8 Progressive Medical Research Port Orange Florida United States 32127
    9 Intercoastal Medical Group Sarasota Florida United States 34239
    10 Stedman Clinical Trials Tampa Florida United States 33613
    11 Indiana University School of Medicine Indianapolis Indiana United States 46202
    12 Josephson Wallack Munshower Neurology, PC Indianapolis Indiana United States 46256
    13 The University of Kansas - Clinical Research Center Fairway Kansas United States 66205
    14 Cotton O'Neil Mulvane Topeka Kansas United States 66606
    15 Boston Center for Memory Newton Massachusetts United States 02459
    16 Washington University Saint Louis Missouri United States 63110
    17 Las Vegas Medical Research Las Vegas Nevada United States 89113
    18 Advanced Memory Research Institute of New Jersey Toms River New Jersey United States 08755
    19 Guilford Neurologic Research, PA Greensboro North Carolina United States 27405
    20 Ohio State University Medical Center Columbus Ohio United States 43221
    21 Neurology Diagnostics, Inc. Dayton Ohio United States 45459
    22 Abington Neurological Associates, Ltd. Abington Pennsylvania United States 19001
    23 Rhode Island Hospital Providence Rhode Island United States 02903
    24 National Clinical Research, Inc Richmond Virginia United States 23294
    25 Bruyère Research Institute Ottawa Ontario Canada K1N 5C8
    26 Toronto Memory Program Toronto Ontario Canada M3B 2S7
    27 Clinique de la Mémoire de l'Outaouais Gatineau Quebec Canada J8T 8J1
    28 Diex Recherche Sherbrooke Inc. Sherbrooke Quebec Canada J1L 0H8

    Sponsors and Collaborators

    • Eli Lilly and Company

    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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT04640077
    Other Study ID Numbers:
    • 17447
    • I5T-MC-AACH
    First Posted:
    Nov 23, 2020
    Last Update Posted:
    May 26, 2022
    Last Verified:
    May 15, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of May 26, 2022