Trial Outcomes & Findings for A Study to Evaluate Safety, Tolerability, and Efficacy of Lecanemab in Subjects With Early Alzheimer's Disease (NCT NCT01767311)

This study has been conducted in two phases: Core Study Phase and an Open-Label Extension (OLE) Phase. Participants took part in the Core study at 149 investigative sites across the North America, Europe and Asia-Pacific. The OLE Phase was conducted at 56 investigative sites across the United States, Europe and Asia-Pacific.

A total of 3267 participants were screened, of which 2411 participants were screen failures, and 856 participants were randomized. Out of 856, 854 participants were treated in Core Study Phase, and 180 participants were enrolled and treated in OLE Phase.

A Study to Evaluate Safety, Tolerability, and Efficacy of Lecanemab in Subjects With Early Alzheimer's Disease

The ADCOMS is a composite score that comprises 4/14 items from the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), 2 items from the Mini Mental State Examination (MMSE), and all items from the Clinical Dementia Rating (CDR). Composite score is derived from the variables from the 12 items, and ranges from 0 to 1.97, where higher score means greater impairment. Change from baseline was analyzed using Bayesian analysis. Data presented are posterior mean and posterior standard deviation.

A TEAE is defined as an AE that emerged during treatment or within 90 days following the last dose of study drug, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening (that is, the participant is at immediate risk of death from the adverse event as it occurs, this does not include an event that, has it occurred in a more severe form or is allowed to continue, might have cause death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect (in the child of a participant who is exposed to the study drug).

A TEAE is defined as an AE that emerged during treatment or within 30 days following the last dose of study drug, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening (that is, the participant is at immediate risk of death from the adverse event as it occurs, this does not include an event that, has it occurred in a more severe form or is allowed to continue, might have cause death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect (in the child of a participant who is exposed to the study drug).

Amyloid plaque load was identified by PET using 2 tracers (florbetapir and flutemetamol). The imaging uptake was determined via standard uptake value ratio (SUVr) versus a reference region. The SUVr is a quantitative tool and refers to the ratio of the global cortical average as compared to a reference region of choice. Whole cerebellum mask was used as the reference region of choice in this study. PET SUVr values were converted to Centiloid units. 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.

The ADCOMS is a composite score that comprises 4/14 items from the ADAS-cog, 2 items from the MMSE, and all items from the CDR. Composite score is derived from the variables from the 12 items, and ranges from 0 to 1.97, where higher score means greater impairment.

The CDR is a clinical scale that describes 5 degrees of impairment in performance on each of 6 categories of function including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. The ratings of degree of impairment obtained on each of the 6 categories of function are synthesized into 1 global rating of dementia CDR score (ranging from 0 to 3). A sum of boxes score provides an additional measure of change where each category has a maximum possible score of 3 points and the total score is a sum of the category scores giving a total possible score of 0 to 18 with higher scores indicating more impairment.

The ADAS-Cog is a cognitive scale which evaluates 14 items- memory (word recall, delayed word recall, and word recognition), reasoning (following commands), language (naming, comprehension), orientation, ideational praxis (placing letter in envelope), constructional praxis (copying geometric designs), spoken language, language comprehension, word finding difficulty, ability to remember test instructions, maze, and number cancellation. The total score ranges from 0 to 90. Higher score indicates greater cognitive impairment.

The measurement of the amyloid proteins- Aβ(1-42) (amyloid beta monomer from amino acid 1 to 42), total (t)-tau, and phospho (p)-tau in CSF have been shown to be important biomarkers for alzheimer's disease.

Total hippocampal volume is measured by volumetric magnetic resonance imaging (vMRI). Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Total hippocampal volume is calculated by summing up right and left hippocampal volumes.

Left and right hippocampal volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Left and right hippocampal volumes represent a summary measure in the left and right hippocampal regions.

Whole brain volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Whole brain volume represents a summary measure of total brain parenchyma which includes the cerebrum, basal ganglia, diencephalon, and cerebellum.

Total ventricular volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Total ventricular volume represents a summary measure of total including right and left lateral ventricles, third ventricle and fourth ventricle of brain.

Amyloid plaque load was identified by PET using 2 tracers (florbetapir and flutemetamol). The imaging uptake was determined via standard uptake value ratio (SUVr) versus a reference region. The SUVr is a quantitative tool and refers to the ratio of the global cortical average as compared to a reference region of choice. Whole cerebellum mask was used as the reference region of choice in this study. PET SUVr values were converted to Centiloid units. 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. Change from OLE baseline was analyzed using the Mixed Model for Repeated Measures (MMRM) with Core Study treatment group, visit, Core Study treatment group by visit interaction, APOE4 status as fixed effects, and OLE baseline value and Gap duration as covariates.

Amyloid plaque load was identified by PET using 2 tracers (florbetapir and flutemetamol). The imaging uptake was determined via standard uptake value ratio (SUVr) versus a reference region. The SUVr is a quantitative tool and refers to the ratio of the global cortical average as compared to a reference region of choice. Whole cerebellum mask was used as the reference region of choice in this study. PET SUVr values were converted to Centiloid units. 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. Change from end of core study at the baseline of OLE phase was summarized using change from core study baseline at each visit.

Percentage of amyloid positive participants over time was reported. Participants who had Amyloid PET (using Centiloid scales) values greater than or equal to 30.00 were considered as amyloid positive.