Clinical trial NCT06976203: A Study to Evaluate the Efficacy and Safety of KarXT + KarX-EC for Cognitive Impairment in Alzheimer's Disease (MINDSET 2)
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of KarXT + KarX-EC for the Treatment of Cognitive Impairment Associated With Mild to Moderate Alzheimer's Disease (MINDSET 2)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Alzheimer's Disease
Keywords: Dementia
Cognitive Impairment
Kar-XT
KarX-EC
Mild Alzheimer's Disease
Moderate Alzheimer's Disease
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2025-05-16
Enrollment: 586
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of KarXT + KarX-EC for cognitive impairment in Alzheimer's Disease


Eligibility criteria: Inclusion Criteria

* Participants must have a confirmed diagnosis of Alzheimer's disease (AD), specifically at the mild (stage 4) or moderate (stage 5) dementia stages, as defined by the National Institute on Aging and Alzheimer's Association (NIA-AA) core clinical criteria. The diagnosis of AD pathology must be confirmed through the 2024 revised NIA-AA Workgroup criteria using a stepwise diagnostic approach.
* Participants must have an Mini-Mental State Examination (MMSE) score ranging from 12 through 22, inclusive, at the time of screening.
* Participants must have a designated caregiver who maintains adequate contact (around 10 hours per week or more) and is willing to attend all study visits. The caregiver must also be responsible for reporting on the participant's condition, overseeing medication compliance, and consenting to their involvement in both their own and the participant's study-related activities.
* Participants on acetyl choline esterase inhibitors (AChEIs) and/or memantine, must have been on a stable dosage for at least 12 weeks prior to screening, and agree to maintain this stable dose for the study duration.

Exclusion Criteria

* Participants must not present with any significant or severe medical conditions that could compromise their safety, the ability to comply with or complete the study, or the integrity of the study results. This includes any grade of hepatic impairment.
* Participants must not have any primary psychiatric diagnoses such as major depression, schizoaffective disorder, or bipolar disorder, and those with severe psychiatric symptoms that could complicate the interpretation of treatment effects, impair cognitive assessment, or impact study completion.
* Participants must not have a history of schizophrenia or other chronic psychosis, as well as those who have previously been exposed to KarXT or are currently undergoing treatment with disease-modifying anti-amyloid therapies for AD within the past 6 months prior to screening.
* Participants must not have significant pathological findings on brain magnetic resonance imaging (MRI) at screening that could affect safety or interfere with study procedures.
* Other protocol-defined Inclusion/Exclusion criteria apply.

Primary outcomes:
measure: Change from baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11)
timeFrame: At week 24
measure: Clinician's Interview-Based Impression Plus Caregiver Input (CIBIC+)
timeFrame: At week 24
Secondary outcomes:
measure: Change from baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL)
timeFrame: At week 24
measure: Change from baseline in neuro psychiatric inventory (NPI) total score
timeFrame: At week 24
measure: Number of participants with adverse events (AEs)
timeFrame: At week 24
measure: Number of participants with serious adverse events (SAEs)
timeFrame: At week 24
measure: Number of participants with adverse event of special interest (AESIs)
timeFrame: At week 24
measure: Number of participants with AEs leading to study intervention discontinuation
timeFrame: At week 24
measure: Number of participants with AEs leading to study discontinuation
timeFrame: At week 24
measure: Number of participants with AEs leading to death
timeFrame: At week 24
measure: Number of participants with clinically significant changes in vital signs
timeFrame: At week 24
measure: Number of participants with clinically significant changes in electrocardiogram (ECG) tests
timeFrame: At week 24
measure: Number of participants with clinically significant changes in Columbia-Suicide Severity Rating Scale (C-SSRS) tests
timeFrame: At week 24
measure: Number of participants with clinically significant changes in weight
timeFrame: At week 24
measure: Number of participants with clinically significant changes in safety laboratory tests
timeFrame: At week 24
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: Local Institution - 0072
state: California
city: Inglewood
country: United States
facility: Local Institution - 0091
state: California
city: Irvine
country: United States
facility: Local Institution - 0095
state: California
city: Palo Alto
country: United States
facility: Local Institution - 0083
state: California
city: San Diego
country: United States
facility: Local Institution - 0069
state: California
city: Denver
country: United States
facility: Local Institution - 0088
state: Colorado
city: Fort Myers
country: United States
facility: Local Institution - 0090
state: Florida
city: Hallandale Beach
country: United States
facility: Local Institution - 0086
state: Florida
city: Jacksonville
country: United States
facility: Local Institution - 0092
state: Florida
city: Sarasota
country: United States
facility: Local Institution - 0082
state: Florida
city: Tampa
country: United States
facility: Local Institution - 0084
state: Florida
city: The Villages
country: United States
facility: Local Institution - 0114
state: Florida
city: Wellington
country: United States
facility: Local Institution - 0089
state: Florida
city: Chicago
country: United States
facility: Local Institution - 0093
state: Illinois
city: Springfield
country: United States
facility: Local Institution - 0070
state: Illinois
city: Indianapolis
country: United States
facility: Local Institution - 0071
state: Indiana
city: Watertown
country: United States
facility: Local Institution - 0080
state: Massachusetts
city: Farmington Hills
country: United States
facility: Local Institution - 0073
state: Michigan
city: Hattiesburg
country: United States
facility: Local Institution - 0085
state: Mississippi
city: Springfield
country: United States
facility: Local Institution - 0094
state: New Jersey
city: West Long Branch
country: United States
facility: Local Institution - 0075
state: New Jersey
city: Albany
country: United States
facility: Local Institution - 0077
state: New York
city: Amherst
country: United States
facility: Local Institution - 0068
state: New York
city: Buffalo
country: United States
facility: Local Institution - 0087
state: New York
city: Lake Success
country: United States
facility: Local Institution - 0078
state: New York
city: Plymouth Meeting
country: United States
facility: Local Institution - 0105
state: Pennsylvania
city: Dallas
country: United States
facility: Local Institution - 0081
state: Texas
city: Round Rock
country: United States
facility: Local Institution - 0079
state: Texas
city: Renton
country: United States
facility: Local Institution - 0076
state: Washington
city: ABB
country: Argentina
facility: Local Institution - 0029
state: Ciudad Autónoma De Buenos Aires
city: Cordoba
country: Argentina
facility: Local Institution - 0027
state: Córdoba
city: Buenos Aires
country: Argentina
facility: Local Institution - 0025
city: Córdoba
country: Argentina
facility: Local Institution - 0028
city: Córdoba
country: Argentina
facility: Local Institution - 0030
city: Mendoza
country: Argentina
facility: Local Institution - 0026
city: Brisbane
country: Australia
facility: Local Institution - 0055
state: Queensland
city: Sippy Downs
country: Australia
facility: Local Institution - 0053
state: Queensland
city: Southport
country: Australia
facility: Local Institution - 0056
state: Queensland
city: Ivanhoe
country: Australia
facility: Local Institution - 0054
state: Victoria
city: Fortaleza
country: Brazil
facility: Local Institution - 0115
state: Ceará
city: Maringa
country: Brazil
facility: Local Institution - 0101
state: Paraná
city: Rio De Janeiro
country: Brazil
facility: Local Institution - 0099
city: São Paulo
country: Brazil
facility: Local Institution - 0100
city: Oulu
country: Finland
facility: Local Institution - 0022
state: Pohjois-Pohjanmaa
city: Helsinki
country: Finland
facility: Local Institution - 0007
state: Uusimaa
city: Turku
country: Finland
facility: Local Institution - 0009
state: Varsinais-Suomi
city: Helsinki
country: Finland
facility: Local Institution - 0006
city: Kuopio
country: Finland
facility: Local Institution - 0008
city: Strasbourg
country: France
facility: Local Institution - 0018
state: Alsace
city: Marseille
country: France
facility: Local Institution - 0015
state: Bouches-du-Rhône
city: Toulouse
country: France
facility: Local Institution - 0013
state: Haute-Garonne
city: Rennes
country: France
facility: Local Institution - 0019
state: Ille-et-Vilaine
city: Nancy
country: France
facility: Local Institution - 0016
state: Meurthe-et-Moselle
city: Lille
country: France
facility: Local Institution - 0021
state: Nord-Pas-de-Calais
city: Bron
country: France
facility: Local Institution - 0020
state: Rhône
city: Gleize
country: France
facility: Local Institution - 0017
state: Rhône
city: Bordeaux
country: France
facility: Local Institution - 0012
city: Paris
country: France
facility: Local Institution - 0014
city: Paris
country: France
facility: Local Institution - 0036
city: Paris
country: France
facility: Local Institution - 0102
city: Munich
country: Germany
facility: Local Institution - 0004
state: Bayern
city: Bad Homburg
country: Germany
facility: Local Institution - 0024
state: Hessen
city: Göttingen
country: Germany
facility: Local Institution - 0023
state: Niedersachsen
city: Chemnitz
country: Germany
facility: Local Institution - 0001
state: Sachsen
city: Köln
country: Germany
facility: Local Institution - 0002
city: Ulm
country: Germany
facility: Local Institution - 0003
city: Patras
country: Greece
facility: Local Institution - 0109
state: Achaḯa
city: Chaidari
country: Greece
facility: Local Institution - 0060
state: Attikí
city: Marousi
country: Greece
facility: Local Institution - 0061
state: Attikí
city: Ioannina
country: Greece
facility: Local Institution - 0059
state: Ioánnina
city: Thessaloniki
country: Greece
facility: Local Institution - 0110
city: Napoli
country: Italy
facility: Local Institution - 0057
state: Campania
city: Foggia
country: Italy
facility: Local Institution - 0058
city: Roma
country: Italy
facility: Local Institution - 0067
city: Kawasaki
country: Japan
facility: Local Institution - 0106
state: Kanagawa
city: Ina
country: Japan
facility: Local Institution - 0038
state: Nagano
city: Kashiwazaki
country: Japan
facility: Local Institution - 0033
state: Niigata
city: Kurashiki
country: Japan
facility: Local Institution - 0034
state: Okayama
city: Osaka-Shi
country: Japan
facility: Local Institution - 0035
state: Osaka
city: Yoshinogari
country: Japan
facility: Local Institution - 0031
state: Saga
city: Wako
country: Japan
facility: Local Institution - 0037
state: Saitama
city: Wako
country: Japan
facility: Local Institution - 0112
state: Saitama
city: Kyoto
country: Japan
facility: Local Institution - 0107
city: 's-Hertogenbosch
country: Netherlands
facility: Local Institution - 0011
state: Noord-Brabant
city: Amsterdam
country: Netherlands
facility: Local Institution - 0096
state: Noord-Holland
city: Zwolle
country: Netherlands
facility: Local Institution - 0098
state: Overijssel
city: Wrocław
country: Poland
facility: Local Institution - 0064
state: Dolnośląskie
city: Lublin
country: Poland
facility: Local Institution - 0108
state: Lubelskie
city: Oswiecim
country: Poland
facility: Local Institution - 0066
state: MA
city: Katowice
country: Poland
facility: Local Institution - 0065
state: Śląskie
city: Torres Vedras
country: Portugal
facility: Local Institution - 0050
state: Lisboa
city: Matosinhos
country: Portugal
facility: Local Institution - 0104
state: Porto
city: Braga
country: Portugal
facility: Local Institution - 0051
city: Coimbra
country: Portugal
facility: Local Institution - 0049
city: Guimarães
country: Portugal
facility: Local Institution - 0063
city: Porto
country: Portugal
facility: Local Institution - 0052
city: Bayamon
country: Puerto Rico
facility: Local Institution - 0074
city: Bucharest
country: Romania
facility: Local Institution - 0039
state: București
city: Bucharest
country: Romania
facility: Local Institution - 0040
state: București
city: Constanta
country: Romania
facility: Local Institution - 0113
state: Constanța
city: București
country: Romania
facility: Local Institution - 0042
city: Sanpetru /Brasov
country: Romania
facility: Local Institution - 0041
city: Barcelona
country: Spain
facility: Local Institution - 0062
state: Barcelona [Barcelona]
city: Santander
country: Spain
facility: Local Institution - 0046
state: Cantabria
city: Pozuelo de Alarcon
country: Spain
facility: Local Institution - 0047
state: Madrid
city: San Sebastián
country: Spain
facility: Local Institution - 0043
state: País Vasco
city: Valencia
country: Spain
facility: Local Institution - 0044
state: Valenciana, Comunitat
city: Madrid
country: Spain
facility: Local Institution - 0048
city: Madrid
country: Spain
facility: Local Institution - 0045
city: Manchester
country: United Kingdom
facility: Local Institution - 0097
state: England
city: Kippax
country: United Kingdom
facility: Local Institution - 0111
state: Leeds
city: London
country: United Kingdom
facility: Local Institution - 0116
state: London, City Of
city: Edinburgh
country: United Kingdom
facility: Local Institution - 0103
state: Midlothian
city: Oxford
country: United Kingdom
facility: Local Institution - 0010
state: Oxfordshire
city: Birmingham
country: United Kingdom
facility: Local Institution - 0005
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: