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)

Overview

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

Interventions

• Drug KarXT
  Specified dose on specified days
• Drug KarX-EC
  Specified dose on specified days
• Other Placebo
  Specified dose on specified days

Primary outcome measures

• Change from baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11) [Time frame: At week 24]
• Clinician's Interview-Based Impression Plus Caregiver Input (CIBIC+) [Time frame: At week 24]

Secondary outcome measures (12)

• Change from baseline in Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL) [Time frame: At week 24]
• Change from baseline in neuro psychiatric inventory (NPI) total score [Time frame: At week 24]
• Number of participants with adverse events (AEs) [Time frame: At week 24]
• Number of participants with serious adverse events (SAEs) [Time frame: At week 24]
• Number of participants with adverse event of special interest (AESIs) [Time frame: At week 24]
• Number of participants with AEs leading to study intervention discontinuation [Time frame: At week 24]
• Number of participants with AEs leading to study discontinuation [Time frame: At week 24]
• Number of participants with AEs leading to death [Time frame: At week 24]
• Number of participants with clinically significant changes in vital signs [Time frame: At week 24]
• Number of participants with clinically significant changes in electrocardiogram (ECG) tests [Time frame: At week 24]
• Number of participants with clinically significant changes in Columbia-Suicide Severity Rating Scale (C-SSRS) tests [Time frame: At week 24]
• Number of participants with clinically significant changes in weight [Time frame: At week 24]

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, urinary retention, active biliary disease, moderate-severe renal impairment (eGFR of <50 mL/min), and unstable hypertension or tachycardia.
• 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 reflect significant pathology other than AD or could affect safety or interfere with study procedures.
• Other protocol-defined Inclusion/Exclusion criteria apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 28 centers

• Healthy Brain Clinic — Long Beach
• Anderson Clinical Research — Redlands
• Mountain Neurological Research Center — Basalt
• Georgetown University Medical Center — Washington D.C.
• JEM Research Institute — Atlantis
• VIN-Julie Schwartzbard — Aventura
• Merritt Island Medical Research, LLC — Merritt Island
• Renstar Medical Research — Ocala
• … and 20 more centers

Canada · 8 centers

• OCT Research ULC — Kelowna
• Richmond Clinical Trials — Richmond
• Centricity Research Halifax Multispecialty — Halifax
• Ottawa Memory Clinic — Ottawa
• Toronto Memory Program — Toronto
• MoCA Research and Innovation Inc. — Greenfield Park
• Diex Recherche Victoriaville — Victoriaville
• ALPHA Recherche Clinique — Québec

Czechia · 7 centers

• Neuro Health Centrum — Brno
• AGE Centrum — Olomouc
• A-Shine — Pilsen
• Local Institution - 0224 — Prague
• Neuropsychiatrie — Prague
• Local Institution - 0222 — Prague
• Vestra Clinics — Rychnov nad Kněžnou

France · 7 centers

• Local Institution - 0295 — Nice
• Local Institution - 0289 — Toulouse
• Local Institution - 0290 — Rouen
• Local Institution - 0291 — Montpellier
• Local Institution - 0299 — Reims
• Local Institution - 0293 — Villeurbanne
• Local Institution - 0294 — Dijon

South Korea · 7 centers

Center list to be confirmed — check the primary protocol.

Germany · 6 centers

• Universitätsklinikum Münster - Albert Schweitzer Campus — Münster
• Universitätsmedizin Johannes Gutenberg Universität Mainz — Mainz
• Charite-Universitaetsmedizin Berlin - Campus Benjamin Franklin (CBF) — Berlin
• Local Institution - 0277 — Bremen
• Local Institution - 0275 — Hamburg
• TUM Klinikum — Munich

Spain · 6 centers

Center list to be confirmed — check the primary protocol.

Argentina · 5 centers

• Fundación para el Estudio y Tratamiento de Enfermedades Mentales (FETEM) — Buenos Aires
• Local Institution - 0271 — Buenos Aires
• Fundación Lennox - Instituto Modelo de Neurología — Córdoba
• Sanatorio Morra S.A. — Córdoba
• Instituto Kremer — Córdoba

Australia · 5 centers

• Southern Neurology — Kogarah
• KARA Institute for Neurological Diseases — Macquarie Park
• NeuroCentrix — Carlton
• Neurodegenerative Disorders Research — Perth
• St Vincent's Hospital Sydney Limited — Darlinghurst

India · 5 centers

Center list to be confirmed — check the primary protocol.

Romania · 5 centers

Center list to be confirmed — check the primary protocol.

Brazil · 4 centers

• Local Institution - 0168 — Brasília
• Instituto de Neurologia de Curitiba — Curitiba
• Local Institution - 0266 — Aracaju
• Hospital das Clinicas FMUSP — São Paulo

Chile · 4 centers

• Local Institution - 0094 — Santiago
• Local Institution - 0089 — Santiago
• Local Institution - 0241 — Santiago
• Local Institution - 0230 — Antofagasta

Greece · 4 centers

• University General Hospital of Alexandroupoli — Alexandroupoli
• Local Institution - 0256 — Athens
• Aiginiteio University Hospital — Athens
• … and 1 more center

Italy · 4 centers

Center list to be confirmed — check the primary protocol.

Poland · 4 centers

Center list to be confirmed — check the primary protocol.

Croatia · 3 centers

• Local Institution - 0215 — Zagreb
• Poliklinika Neuron — Zagreb
• Klinika za psihijatriju "Vrapče" — Zagreb

Netherlands · 3 centers

Center list to be confirmed — check the primary protocol.

Puerto Rico · 1 center

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06976216 · CN012-0051 · 2025-520746-30 · U1111-1317-4462

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗