Clinical trial NCT06976216: A Study to Evaluate the Efficacy and Safety of KarXT + KarX-EC for Cognitive Impairment in Alzheimer's Disease
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 1)
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: Long Beach
country: United States
facility: Local Institution - 0173
state: California
city: Redlands
country: United States
facility: Local Institution - 0008
state: California
city: Basalt
country: United States
facility: Local Institution - 0025
state: Colorado
city: Washington
country: United States
facility: Local Institution - 0024
state: District of Columbia
city: Atlantis
country: United States
facility: Local Institution - 0154
state: Florida
city: Aventura
country: United States
facility: Local Institution - 0128
state: Florida
city: Merritt Island
country: United States
facility: Local Institution - 0023
state: Florida
city: Ocala
country: United States
facility: Local Institution - 0055
state: Florida
city: Stuart
country: United States
facility: Local Institution - 0263
state: Florida
city: The Villages
country: United States
facility: Local Institution - 0184
state: Florida
city: Columbus
country: United States
facility: Local Institution - 0016
state: Georgia
city: Gainesville
country: United States
facility: Local Institution - 0125
state: Georgia
city: Chicago
country: United States
facility: Local Institution - 0109
state: Illinois
city: Elk Grove Village
country: United States
facility: Local Institution - 0054
state: Illinois
city: Newton
country: United States
facility: Local Institution - 0009
state: Massachusetts
city: Watertown
country: United States
facility: Local Institution - 0259
state: Massachusetts
city: Saint Paul
country: United States
facility: Local Institution - 0110
state: Minnesota
city: Toms River
country: United States
facility: Local Institution - 0123
state: New Jersey
city: New York
country: United States
facility: Local Institution - 0101
state: New York
city: Syracuse
country: United States
facility: Local Institution - 0202
state: New York
city: Charlotte
country: United States
facility: Local Institution - 0007
state: North Carolina
city: Columbus
country: United States
facility: Local Institution - 0073
state: Ohio
city: Dayton
country: United States
facility: Local Institution - 0026
state: Ohio
city: Portland
country: United States
facility: Local Institution - 0067
state: Oregon
city: Abington
country: United States
facility: Local Institution - 0004
state: Pennsylvania
city: East Providence
country: United States
facility: Local Institution - 0056
state: Rhode Island
city: Cordova
country: United States
facility: Local Institution - 0099
state: Tennessee
city: Knoxville
country: United States
facility: Local Institution - 0152
state: Tennessee
city: Beaumont
country: United States
facility: Local Institution - 0018
state: Texas
city: Banfield
country: Argentina
facility: Local Institution - 0088
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Local Institution - 0001
state: Ciudad Autonoma De Buenos Aires
city: Buenos Aires
country: Argentina
facility: Local Institution - 0271
city: Córdoba
country: Argentina
facility: Local Institution - 0228
city: Córdoba
country: Argentina
facility: Local Institution - 0232
city: Córdoba
country: Argentina
facility: Local Institution - 0085
city: Kogarah
country: Australia
facility: Local Institution - 0279
state: New South Wales
city: Macquarie Park
country: Australia
facility: Local Institution - 0245
state: New South Wales
city: Sydney
country: Australia
facility: Local Institution - 0244
state: New South Wales
city: Carlton
country: Australia
facility: Local Institution - 0242
state: Victoria
city: Perth
country: Australia
facility: Local Institution - 0243
state: Western Australia
city: Brasília
country: Brazil
facility: Local Institution - 0168
state: Distrito Federal
city: Curitiba
country: Brazil
facility: Local Institution - 0180
state: Paraná
city: Aracaju
country: Brazil
facility: Local Institution - 0266
state: Sergipe
city: São Paulo
country: Brazil
facility: Local Institution - 0165
city: Kelowna
country: Canada
facility: Local Institution - 0233
state: British Columbia
city: Richmond
country: Canada
facility: Local Institution - 0234
state: British Columbia
city: Halifax
country: Canada
facility: Local Institution - 0236
state: Nova Scotia
city: Ottawa
country: Canada
facility: Local Institution - 0237
state: Ontario
city: Toronto
country: Canada
facility: Local Institution - 0235
state: Ontario
city: Greenfield Park
country: Canada
facility: Local Institution - 0238
state: Quebec
city: Victoriaville
country: Canada
facility: Local Institution - 0239
state: Quebec
city: Quebec
country: Canada
facility: Local Institution - 0264
city: Antofagasta
country: Chile
facility: Local Institution - 0230
state: AN
city: Providencia
country: Chile
facility: Local Institution - 0272
state: Región Metropolitana De Santiago
city: Santiago
country: Chile
facility: Local Institution - 0094
state: Región Metropolitana De Santiago
city: Santiago
country: Chile
facility: Local Institution - 0089
state: Región Metropolitana De Santiago
city: Santiago
country: Chile
facility: Local Institution - 0241
state: Región Metropolitana De Santiago
city: Zagreb
country: Croatia
facility: Local Institution - 0215
state: Grad Zagreb
city: Zagreb
country: Croatia
facility: Local Institution - 0284
state: Grad Zagreb
city: Osijek
country: Croatia
facility: Local Institution - 0216
city: Rijeka
country: Croatia
facility: Local Institution - 0267
city: Zagreb
country: Croatia
facility: Local Institution - 0240
city: Brno
country: Czechia
facility: Local Institution - 0227
state: Brno-město
city: Olomouc
country: Czechia
facility: Local Institution - 0225
state: Olomoucký Kraj
city: Plzen
country: Czechia
facility: Local Institution - 0221
state: Plzeň-město
city: Prague
country: Czechia
facility: Local Institution - 0223
state: Praha 6
city: Praha
country: Czechia
facility: Local Institution - 0224
state: Praha 6
city: Praha
country: Czechia
facility: Local Institution - 0222
state: Praha 8
city: Rychnov nad Kněžnou
country: Czechia
facility: Local Institution - 0226
city: München
country: Germany
facility: Local Institution - 0217
state: Bayern
city: Münster
country: Germany
facility: Local Institution - 0219
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: Local Institution - 0276
state: Rheinland-Pfalz
city: Berlin
country: Germany
facility: Local Institution - 0218
city: Bremen
country: Germany
facility: Local Institution - 0277
city: Hamburg
country: Germany
facility: Local Institution - 0275
city: Athens
country: Greece
facility: Local Institution - 0256
state: Attikí
city: Athens
country: Greece
facility: Local Institution - 0274
state: Attikí
city: Thessaloniki
country: Greece
facility: Local Institution - 0251
state: Thessaloníki
city: Larissa
country: Greece
facility: Local Institution - 0257
state: Thessalía
city: Alexandroupolis
country: Greece
facility: Local Institution - 0281
city: Bengaluru
country: India
facility: Local Institution - 0288
state: Karnataka
city: Hyderabad
country: India
facility: Local Institution - 0282
state: Telangana
city: Hyderabad
country: India
facility: Local Institution - 0285
state: Telangana
city: Varanasi
country: India
facility: Local Institution - 0287
state: Uttar Pradesh
city: Kolkata
country: India
facility: Local Institution - 0286
state: West Bengal
city: Milano
country: Italy
facility: Local Institution - 0249
state: Lombardia
city: Milano
country: Italy
facility: Local Institution - 0246
state: Lombardia
city: Monza
country: Italy
facility: Local Institution - 0248
state: Lombardia
city: Brescia
country: Italy
facility: Local Institution - 0247
city: Gwangju-si
country: Korea, Republic of
facility: Local Institution - 0209
state: Kwangju-Kwangyǒkshi
city: Seongnam
country: Korea, Republic of
facility: Local Institution - 0214
state: Kyǒnggi-do
city: Gangseo-gu
country: Korea, Republic of
facility: Local Institution - 0211
state: Seoul-teukbyeolsi [Seoul]
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0213
state: Seoul-teukbyeolsi [Seoul]
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0208
state: Seoul-teukbyeolsi [Seoul]
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0210
state: Seoul-teukbyeolsi [Seoul]
city: Seoul
country: Korea, Republic of
facility: Local Institution - 0212
state: Seoul-teukbyeolsi [Seoul]
city: Torun
country: Poland
facility: Local Institution - 0261
state: Kujawsko-pomorskie
city: Bialystok
country: Poland
facility: Local Institution - 0280
state: Podlaskie
city: Gdansk
country: Poland
facility: Local Institution - 0260
state: Pomorskie
city: Poznań
country: Poland
facility: Local Institution - 0262
state: Wielkopolskie
city: San Juan
country: Puerto Rico
facility: Local Institution - 0181
city: Bucharest
country: Romania
facility: Local Institution - 0278
state: București
city: Bucharest
country: Romania
facility: Local Institution - 0269
state: București
city: Bucharest
country: Romania
facility: Local Institution - 0270
state: București
city: Bucharest
country: Romania
facility: Local Institution - 0273
state: București
city: Iași
country: Romania
facility: Local Institution - 0268
city: Seville
country: Spain
facility: Local Institution - 0255
state: Andalucía
city: Sant Cugat del Vallès
country: Spain
facility: Local Institution - 0254
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Local Institution - 0258
state: Catalunya [Cataluña]
city: Lleida
country: Spain
facility: Local Institution - 0253
state: Lleida [Lérida]
city: Pamplona
country: Spain
facility: Local Institution - 0252
state: Navarra
city: Madrid
country: Spain
facility: Local Institution - 0250
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: