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

Alzheimer Disease Clinical Trial

Official title:

Assessment of Safety, Tolerability and Efficacy of LY3002813 in Early Symptomatic Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03367403
• Other study ID #: 16933
• Secondary ID: I5T-MC-AACG
• Status: Completed
• Phase: Phase 2
• Start date: December 18, 2017
• Est. completion date: September 21, 2021

Study information

• Verified date: September 2022
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety, tolerability and efficacy of LY3002813 in early symptomatic Alzheimer's disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 272
• Est. completion date: September 21, 2021
• Est. primary completion date: December 4, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 85 Years

Eligibility

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 or an acceptable historical flortaucipir PET scan within 6 months prior to baseline that meets the central read criteria.

• Meet 18F flortaucipir PET scan eligibility criteria.

• Meet 18F florbetapir PET scan (central read) eligibility criteria.

Exclusion Criteria:

• Have a history of long QT syndrome.

• Have received treatment with a stable dose of an acetylcholinesterase inhibitor (AChEI) and/or memantine for less than 2 months before randomization.

• Contraindication to MRI.

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• Donanemab
Administered IV
• Placebo
Administered IV
• LY3202626
Administered orally

Locations

Country	Name	City	State
Canada	Clinique de la Memoire de l'Outaouais	Gatineau	Quebec
Canada	Bruyere Research Institute	Ottawa	Ontario
Canada	Kawartha Regional Memory Clinic	Peterborough	Ontario
Canada	DIEX Recherche Sherbrooke, Inc	Sherbrooke	Quebec
Canada	Toronto Memory Program	Toronto	Ontario
United States	JEM Research Institute	Atlantis	Florida
United States	Insight Clinical Trials	Beachwood	Ohio
United States	McLean Hospital	Belmont	Massachusetts
United States	The Memory Clinic	Bennington	Vermont
United States	Bradenton Research Center	Bradenton	Florida
United States	Behavioral Health Center Research	Charlotte	North Carolina
United States	Great Lakes Clinical Trials	Chicago	Illinois
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Texas Neurology, PA	Dallas	Texas
United States	Associated Neurologists, PC - Danbury	Danbury	Connecticut
United States	Neurology Diagnostics, Inc.	Dayton	Ohio
United States	Brain Matters Research	Delray Beach	Florida
United States	Alexian Brothers Medical Center	Elk Grove Village	Illinois
United States	Cognition Health	Fairfax	Virginia
United States	University of Kansas Hospital	Fairway	Kansas
United States	Neurology Center of North Orange County	Fullerton	California
United States	Guilford Neurologic Associates	Greensboro	North Carolina
United States	Infinity Clinical Research, LLC	Hollywood	Florida
United States	Houston Methodist	Houston	Texas
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	Josephson Wallack Munshower Neurology	Indianapolis	Indiana
United States	Institute for Memory Impairment & Neurological Disorders	Irvine	California
United States	Irvine Clinical Research Center	Irvine	California
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Las Vegas Medical Research	Las Vegas	Nevada
United States	Merritt Island Medical Research LLC	Merritt Island	Florida
United States	ActivMed Practices & Research, Inc	Methuen	Massachusetts
United States	Miami Jewish Health Systems	Miami	Florida
United States	Pharmax Research Clinic	Miami	Florida
United States	Suncoast Clinical Research	New Port Richey	Florida
United States	Pharmacology Research Institute	Newport Beach	California
United States	Boston Center for Memory	Newton	Massachusetts
United States	Compass Research	Orlando	Florida
United States	Palm Beach Neurological Group	Palm Beach Gardens	Florida
United States	Banner Alzheimer's Institute	Phoenix	Arizona
United States	Donald S Marks	Plymouth	Massachusetts
United States	Quantum Laboratories	Pompano Beach	Florida
United States	Progressive Medical Research	Port Orange	Florida
United States	Butler Hospital	Providence	Rhode Island
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Raleigh Neurology Associates	Raleigh	North Carolina
United States	National Clinical Research - Richmond	Richmond	Virginia
United States	Washington University	Saint Louis	Missouri
United States	Pacific Research Network Inc	San Diego	California
United States	Sharp Mesa Vista Hospital	San Diego	California
United States	Syrentis Clinical Research	Santa Ana	California
United States	Intercoastal Medical Group	Sarasota	Florida
United States	KI Health Partners, LLC d/b/a NE Inst. for Clin. Res.	Stamford	Connecticut
United States	Banner Sun Health Research Institute	Sun City	Arizona
United States	Axiom Research	Tampa	Florida
United States	Stedman Clinical Trials	Tampa	Florida
United States	Compass Research	The Villages	Florida
United States	Advanced Memory Research Institute of New Jersey	Toms River	New Jersey
United States	Cotton O'Neil Clinic	Topeka	Kansas
United States	Abington Neurological Associates	Willow Grove	Pennsylvania
United States	Piedmont Medical Research	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in the Integrated Alzheimer's Disease Rating Scale (iADRS) Score	Integrated Alzheimer's Disease Rating Scale is used to assess whether donanemab slows down the cognitive and functional decline associated with AD compared with placebo. iADRS is a simple linear combination of 13-item 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. Least Squares (LS) Mean value was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, acetylcholinesterase inhibitor (AChEI) and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.	Baseline, 76 Weeks
Secondary	Change From Baseline in the 13-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) Score	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 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 controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, AChEI and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.	Baseline, 76 Weeks
Secondary	Change From Baseline in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) Score	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 controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, AChEI and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.	Baseline, 76 Weeks
Secondary	Change From Baseline in the Mini Mental State Examination (MMSE) Score	MMSE is a brief screening 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 controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, AChEI and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.	Baseline, 76 Weeks
Secondary	Change From Baseline in Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Scale (ADCS-iADL) Score	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 controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, pooled investigator, AChEI and/or memantine use at baseline, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.	Baseline, 76 Weeks
Secondary	Change From Baseline in Brain Amyloid Plaque Deposition as Measured by Florbetapir F18 Positron Emission Tomography (PET) Scan	Florbetapir PET imaging was used as a quantitative amyloid biomarker. Florbetapir 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 areas of the brain 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. Least Squares mean change was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline, baseline-by-visit, and age at baseline.	Baseline, 76 Weeks
Secondary	Change From Baseline in Brain Tau Deposition as Measured by Flortaucipir F18 PET Scan	Flortaucipir PET imaging was used as a quantitative tau biomarker. Flortaucipir 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 two measures: weighted average Standardized Uptake Value Ratio (MUBADA SUVR) in the brain relative to the cerebellum gray as a reference region and the global tau load (TauL) generated using a TauIQ method. Larger weighted average SUVR reflects the larger cortical tau burden relative to cerebellum gray. The TauIQ method quantifies the spatiotemporal accumulation pattern of tau and larger TauL value reflects the larger global tau level in the brain as determined using a TauIQ mathematical framework. Least Squares mean change was controlled for baseline + age + treatment (Type III sum of squares).	Baseline, 76 Weeks
Secondary	Change From Baseline in Brain Volume as Measured by Volumetric Magnetic Resonance Imaging (vMRI)	MRI scans at baseline and at 76 weeks after the first treatment were used to quantitatively estimate change in brain atrophy. Volumetric MRI (vMRI) parameters were measured in 14 brain regions: bilateral cortical, bilateral entorhinal cortex, bilateral hippocampus, bilateral inferior parietal lobe, bilateral isthmus cingulate, bilateral lateral parietal lobe, bilateral medial temporal lobe, bilateral precuneus, bilateral prefrontal lobe, bilateral superior temporal lobe, bilateral ventricles, bilateral whole brain, bilateral whole temporal lobe, and bilateral white matter. The atrophy was assessed by tensor-based morphometry, which captures volume changes within the deformation map. LS Mean value was controlled for fixed, categorical effects of treatment, visit and treatment-by-visit interaction, fixed covariates of baseline, and age at baseline.	Baseline, 76 Weeks

External Links

•   A Study of LY3002813 in Participants With Early Symptomatic Alzheimer's Disease