The aim of this study is to assess the efficacy and safety of GSK4527226 in participants with early Alzheimer's Disease (AD) (including mild cognitive impairment \[MCI\] and mild dementia due to AD) of 2 dose levels of GSK4527226 compared to placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
367
GSK4527226 will be administered.
Placebo will be administered.
Change from Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score for Dose 1 vs Placebo Across Weeks 52, 64 and 76
The CDR-SB score is a quantitative general index that provides more precision in participants with mild dementia. The CDR scale is a clinician-rated dementia staging system tracks the progression of. cognitive impairment in 6 categories (memory, orientation, judgment, and problem solving, community affairs, home and hobbies, and personal care). Each category is scored on a 5- point scale in which None=0, Questionable=0.5, Mild=1, Moderate=2, and Severe=3. The CDR-SB is obtained by adding the ratings in each of the 6 categories and ranges from 0 to 18 with higher scores indicative of greater impairment.
Time frame: Baseline, Week 52, 64 and 76
Change from Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Score for Dose 1 vs Placebo Across Weeks 52, 64 and 76
The iADRS is a composite score that measures both cognition and function. The iADRS comprises scores from the AD Assessment Scale-Cognitive subscale (ADAS-Cog) and the Alzheimers Disease Cooperative Study-instrumental Activities of Daily Living (ADCS-iADL). The iADRS is calculated as a linear combination of the total scores of the ADAS-Cog14 (14-item version of the test that assesses immediate and delayed memory, confrontational naming, ability to follow commands, ideational and constructional praxis, orientation, language, and attention. Higher scores indicate greater impairment) and the ADCS-iADL (score range from 0-49 with higher scores reflecting better performance and lower scores indicating greater functional impairment).
Time frame: Baseline, Weeks 52, 64 and 76
Change from Baseline in ADAS-Cog14 Score for Dose 1 vs Placebo Across Weeks 52, 64 and 76
The AD Assessment Scale-Cognitive subscale (ADAS-Cog14) is a 14-item version of the test that assesses immediate and delayed memory, confrontational naming, ability to follow commands, ideational and constructional praxis, orientation, language, and attention. Score ranges from 0 to 90 and higher scores indicate greater impairment.
Time frame: Baseline, Weeks 52, 64 and 76
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GSK Investigational Site
San Diego, California, United States
GSK Investigational Site
Lake Mary, Florida, United States
GSK Investigational Site
Lake Worth, Florida, United States
GSK Investigational Site
Maitland, Florida, United States
GSK Investigational Site
Miami, Florida, United States
GSK Investigational Site
Orlando, Florida, United States
GSK Investigational Site
Orlando, Florida, United States
GSK Investigational Site
Stuart, Florida, United States
GSK Investigational Site
The Villages, Florida, United States
GSK Investigational Site
The Villages, Florida, United States
...and 87 more locations
Change from Baseline in ADCS-ADL-MCI Score for Dose 1 vs Placebo Across Weeks 52, 64 and 76
The AD Cooperative Study - Activities of Daily Living Scale for use in Mild Cognitive Impairment (ADCS-ADL-MCI). The ADCS-ADL for MCI is a 23-item scale that measures the competence of participants in basic and instrumental activities of daily living. Total scores on the ADCS-ADL-MCI range from 0 to 53 where lower scores indicates greater functional impairment.
Time frame: Baseline, Weeks 52, 64 and 76
Change from Baseline in ADCS-iADL component of ADCS-ADL-MCI Score for Dose 1 vs Placebo Across Weeks 52, 64 and 76
The ADCS-iADL is a subscale which measures instrumental activities of daily living. The ADCS-iADL is derived from the ADCS-ADL-MCI. It has a total score ranging from 0 to 49 with lower scores indicating greater functional impairment.
Time frame: Baseline, Weeks 52, 64 and 76
Change from Baseline in Alzheimer's Disease Composite Score (ADCOMS) for Dose 1 vs Placebo Across Weeks 52, 64 and 76
The ADCOMS is a composite score comprising scores from various items of the Mini-Mental Status Examination (MMSE), ADAS-Cog14, and CDR domains. The MMSE is a brief test used to screen for cognitive impairment. It is routinely used for estimating the severity of cognitive impairment and tracking cognitive changes in an individual over time. It assesses orientation (time and place), registration, attention and calculation, recent memory, language (naming, comprehension, and repetition), and constructional praxis (copying a figure). For ADCOMS a higher score is indicative of greater impairment.
Time frame: Baseline, Weeks 52, 64 and 76