Study Description

Study Design

Groups and Cohorts

Outcome Measures

Primary Outcome Measures

1. Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) (Overall Population) [Baseline, Week 76]
   Integrated Alzheimer's Disease Rating Scale is used to assess whether donanemab slows down the clinical decline associated with AD compared with placebo. iADRS is an integrated assessment of cognition and daily function comprised of items from the ADAS-Cog13 and the Alzheimer's disease cooperative study-instrumental activities of daily living scale (ADCS-iADL). The scale ranges from 0 to 144, where lower scores indicate worse performance and higher score indicates better performance. Least Squares (LS) Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, baseline tau level, and baseline acetylcholinesterase inhibitor (AchI)/Memantine use.
2. Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) (Intermediate (Low-medium) Tau Population) [Baseline, Week 76]
   Integrated Alzheimer's Disease Rating Scale is used to assess whether donanemab slows down the clinical decline associated with AD compared with placebo. iADRS is an integrated assessment of cognition and daily function comprised of items from the Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog13) and the Alzheimer's disease cooperative study-instrumental activities of daily living scale (ADCS-iADL). The scale ranges from 0 to 144, where lower scores indicate worse performance and higher score indicates better performance. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, and baseline AchI/Memantine use.

Secondary Outcome Measures

1. Change From Baseline on the Mini Mental State Examination (MMSE) Score (Overall Population) [Baseline, Week 76]
   MMSE is an instrument used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures). Total score ranges from 0 to 30; lower score indicates greater disease severity. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, baseline tau level, and baseline AchI/Memantine use.
2. Change From Baseline on the Mini Mental State Examination (MMSE) Score (Intermediate (Low-medium) Tau Population) [Baseline, Week 76]
   MMSE is an instrument used to assess cognitive function (orientation, memory, attention, ability to name objects, follow verbal/written commands, write a sentence, and copy figures). Total score ranges from 0 to 30; lower score indicates greater disease severity. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, and baseline AchI/Memantine use.
3. Change From Baseline on the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) (Overall Population) [Baseline, Week 76]
   The ADAS-Cog13 is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS-Cog13 consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS-Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, baseline tau level, and baseline AchI/Memantine use.
4. Change From Baseline on the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) (Intermediate (Low-medium) Tau Population) [Baseline, Week 76]
   The ADAS is a rater administered instrument that was designed to assess the severity of the dysfunction in the cognitive and noncognitive behaviors characteristic of persons with AD. The cognitive subscale of the ADAS-cog consists of 13 items assessing areas of cognitive function most typically impaired in AD: orientation, verbal memory, language, praxis, delayed free recall, digit cancellation. The ADAS-Cog13 scale ranges from 0 to 85. Higher scores indicate greater disease severity. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, and baseline AchI/Memantine use.
5. Change From Baseline on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) (Overall Population) [Baseline, Week 76]
   CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. LS Mean value was adjusted for treatment, visit, treatment-by-visit interaction, and covariates for baseline score, baseline score-by-visit interaction, age at baseline, baseline tau category, pooled investigator, and baseline AchI/Memantine use.
6. Change From Baseline on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) (Intermediate (Low-medium) Tau Population) [Baseline, Week 76]
   CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care. Severity score assigned for each of 6 domains; Total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity. LS Mean value was adjusted for treatment, visit, treatment-by-visit interaction, and covariates for baseline score, baseline score-by-visit interaction, age at baseline, pooled investigator, and baseline AchI/Memantine use.
7. Change From Baseline on the Alzheimer's Disease Cooperative Study - Instrumental Activities of Daily Living (ADCS-iADL) Score (Overall Population) [Baseline, Week 76]
   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 (instrumental activity items 6a, 7-23) of daily living by participants. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, baseline tau level, and baseline AchI/Memantine use.
8. Change From Baseline on the Alzheimer's Disease Cooperative Study - Instrumental Activities of Daily Living (ADCS-iADL) Score (Intermediate (Low-medium) Tau Population) [Baseline, Week 76]
   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 (instrumental activity items 6a, 7-23) of daily living by participants. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean value was adjusted for basis expansion terms (two terms), basis expansion term-by-treatment interaction, and covariates for age at baseline, pooled investigator, and baseline AchI/Memantine use.
9. Change From Baseline in Brain Amyloid Plaque Deposition as Measured by Amyloid Positron Emission Tomography (PET) Scan [Baseline, Week 76]
   Amyloid PET scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in amyloid plaques. Quantitative amyloid burden was first formalized as the average Standardized Uptake Value Ratio (SUVR) in six predetermined cortical brain regions relative to the cerebellum as a reference region. Larger SUVR reflects the larger cortical amyloid burden relative to cerebellum. SUVR values were further calibrated to a centiloid (CL) scale. The Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scan. LS Mean value was adjusted for treatment, visit, treatment-by-visit interaction, and covariates for baseline score, baseline score-by-visit interaction, baseline tau category, and age at baseline.
10. Change From Baseline in Brain Tau Deposition as Measured by Flortaucipir F18 PET Scan [Baseline, Week 76]
    Flortaucipir PET imaging was used as a quantitative tau biomarker. Tau PET scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in aggregated tau neurofibrillary tangles (NFTs). Quantitative tau burden was formalized using Standardized Uptake Value Ratio (SUVR) in frontal lobe relative to the cerebellum gray as a reference region. Larger SUVR reflects larger tau burden in the frontal lobe relative to cerebellum gray. LS Mean value was adjusted for baseline score, screening tau category, age and treatment (Type III sum of squares).
11. Change From Baseline in Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI) [Baseline, Week 76]
    MRI scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in brain volume. Volumetric MRI parameters were measured in bilateral hippocampus, bilateral whole brain, and bilateral ventricles. LS Mean value was adjusted for treatment, visit, treatment-by-visit interaction, and covariates for baseline score, baseline tau category, and age at baseline.
12. Pharmacokinetics (PK): Average Serum Concentration at Steady State of Donanemab [Week 16 to week 20]
    The average serum concentration at steady state, calculated as Cav = AUCtau/tau, where tau is the dosing interval (4 weeks). AUCtau/tau was assessed at week 12, 16, 24, 36, 52, 64 and Cav for the dosing interval from week 16 to week 20 is reported.
13. Number or Participants With Anti-Donanemab Antibodies [Baseline through Week 76]
    Number of participants with treatment-emergent positive Anti-Donanemab antibodies was summarized by treatment group.

Eligibility Criteria

Contacts and Locations

Study Documents (Full Text)

• Documents Provided by Eli Lilly and Company: Study Protocol November 10, 2022
• Documents Provided by Eli Lilly and Company: Statistical Analysis Plan April 20, 2023

More Information

Additional Information

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

Additional Relevant MeSH Terms

• Alzheimer Disease
• Dementia
• Brain Diseases
• Central Nervous System Diseases
• Nervous System Diseases
• Tauopathies
• Neurodegenerative Diseases
• Neurocognitive Disorders
• Mental Disorders