Assessment of Safety, Tolerability, and Efficacy of Donanemab in Early Symptomatic Alzheimer's Disease

ClinicalTrials.gov processed this data on September 20, 2024. Link to the current ClinicalTrials.gov record.

Recruitment Status

ACTIVE, NOT RECRUITING - HAS RESULTS
(See Contacts and Locations)
Verified September 2024 by Eli Lilly and Company

Sponsor

Eli Lilly and Company

Information Provided by (Responsible Party)

Eli Lilly and Company

Clinicaltrials.gov Identifier

NCT04437511
Other Study ID Numbers: 17737
First Submitted: June 17, 2020
First Posted: June 18, 2020
Results First Posted: May 20, 2024
Last Update Posted: September 23, 2024
Last Verified: September 2024
History of Changes

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Tracking Information
First Submitted DateJune 17, 2020
First Posted DateJune 18, 2020
Results First Submitted DateApril 10, 2024
Results First Posted DateMay 20, 2024
Last Update Posted DateSeptember 23, 2024
Study Start DateJune 19, 2020
Actual Primary Completion DateApril 14, 2023
Current Primary Outcome Measures
(submitted: September 20, 2024)
  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.
Change HistoryComplete list of historical versions of study NCT04437511 on ClinicalTrials.gov Archive Site
Current 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.
Current Other Outcome MeasuresNot Provided
Descriptive Information
Brief TitleA Study of Donanemab (LY3002813) in Participants With Early Alzheimer's Disease (TRAILBLAZER-ALZ 2)
Official TitleAssessment of Safety, Tolerability, and Efficacy of Donanemab in Early Symptomatic Alzheimer's Disease
Brief SummaryThe 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 DescriptionTRAILBLAZER-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 amyloid and 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 TypeInterventional
Study PhasePhase 3
Study DesignAllocation: Randomized
Interventional Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Target Follow-Up DurationNot Provided
BiospecimenNot Provided
Sampling MethodNot Provided
Study PopulationNot Provided
Condition
  • Alzheimer Disease
Intervention

Drug: Donanemab

Given IV

Study Groups/Cohorts

Experimental: Donanemab
Participants received 700 milligram (mg) Donanemab every 4 weeks (Q4W) x 3 doses, then 1400 mg Q4W given intravenously (IV) for up to 72 weeks

Intervention:
  • Drug: Donanemab

Placebo Comparator: Placebo
Participants received placebo given IV.

Intervention:
  • Drug: Placebo
Publications *Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment StatusActive, not recruiting
Actual Enrollment
(submitted: September 20, 2024)
1736
Anticipated Study Completion DateAugust 22, 2025
Actual Primary Study Completion DateApril 14, 2023
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/GenderSexes Eligible for Study: All
Ages60 Years to 85 Years (Adult, Older Adult)
Accepts Healthy VolunteersNo
ContactsContact information is only displayed when the study is recruiting subjects
Listed Location CountriesUnited States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, United States, Australia, Australia, Australia, Australia, Australia, Australia, Australia, Australia, Australia, Canada, Canada, Canada, Canada, Canada, Canada, Canada, Canada, Canada, Canada, Canada, Canada, Canada, Canada, Canada, Canada, Canada, Czechia, Czechia, Czechia, Czechia, Czechia, Czechia, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Japan, Netherlands, Netherlands, Netherlands, Netherlands, Poland, Poland, Poland, Poland, Poland, Poland, Poland, Poland, Poland, Poland, Poland, Poland, Poland, Poland, Puerto Rico, Puerto Rico, Puerto Rico, Puerto Rico, United Kingdom, United Kingdom, United Kingdom, United Kingdom
Administrative Information
NCT NumberNCT04437511
Other Study ID Numbers17737
Has Data Monitoring CommitteeYes
U.S FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product: Yes

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

Product Manufactured in and Exported from the U.S.: Not Provided

IPD Sharing StatementPlan to Share IPD: Yes
Responsible PartyEli Lilly and Company, Eli Lilly and Company
Study SponsorEli Lilly and Company
CollaboratorsNot Provided
Investigators
PRS AccountEli Lilly and Company
Verification DateSeptember 2024