A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Safety and Efficacy of KarXT for the Treatment of Psychosis Associated with Alzheimer’s Disease (ADEPT-4)

Karuna Therapeutics, Inc., a Bristol-Myers Squibb company6 个研究点分布在 1 个国家目标入组 366 人开始时间: 2025年11月24日最近更新: 2026年3月16日

试验速览

阶段: 3 期
状态: 尚未招募
发起方
入组人数: 366
试验地点: 6
主要终点: 1. To evaluate the efficacy of KarXT compared with

研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a Phase 3, randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety and efficacy of KarXT in adult participants who are aged 55 to 90 years and have mild to severe AD with moderate to severe psychosis related to AD. Participants may or may not have symptoms of agitation.

Approximately 406 participants will be enrolled to randomize approximately 366 participants (183 participants/arm). The study includes an up to 30-day Screening Period, a 2-week Placebo Run-In Period, a 12-week Randomized Treatment Period, and a Safety Follow-up visit following the end of treatment (EOT)/early termination (ET) if the participant does not enter a long-term open-label extension (OLE) safety study. The total study duration for an individual participant is approximately 22 weeks (Screening Period, Placebo Run-In Period, Randomized Treatment Period, and Safety Follow-up).

研究设计

研究类型: Interventional
分配方式: Randomized
盲法: Participant and Investigator Blinded

入排标准

年龄范围: 55.00 Year(s) 至 90.00 Year(s)（—）
性别: All

入选标准

•Participants are eligible to be included in the study only if all the following criteria apply Is a male or female aged 55 to 90 years inclusive at Screening Visit 1 Participants or their legally acceptable representative must have signed and dated an Institutional Review Board IRB Independent Ethics Committee IEC approved written informed consent form ICF in accordance with regulatory local and institutional guidelines This ICF must be obtained before performing any protocol related procedures that are not part of normal patient care If the participant is deemed not competent to provide IC the following requirements for consent must be met The participant’s legally acceptable representative LAR must provide IC The participant must provide informed assent A diagnosis of AD in accordance with the 2024 National Institute on Aging and Alzheimer’s Association NIA AA criteria with one of the following confirmations of AD pathology Historical evidence of AD diagnosis with amyloid positron emission tomography (PET), A beta 42/40 ratio in CSF, pTau181/A beta 42 ratio in CSF, or pTau217/A beta 42 ratio in plasma using an assay that meets Health Authority requirements If no historical evidence is available or does not satisfy the above requirements: A plasma biomarker will be assessed for eligibility and will meet regulatory requirements for intended use.
•If a plasma biomarker assay cannot be used or if the assay result is inconclusive, conduct one of the following: Amyloid PET A beta 42/40 ratio or pTau181/A beta 42 ratio in CSF using an assay that meets Health Authority-requirements As new CSF or plasma AD diagnostic biomarkers are accepted by regulatory authorities with an indication for diagnosis of AD and/or as an aid in diagnosis of AD, the Sponsor will consider their inclusion.
•Has a magnetic resonance imaging MRI or computed tomography CT scan of the brain completed within the past 5 years taken during or subsequent to the onset of dementia to rule out other central nervous system CNS disease that could account for the dementia syndrome eg major stroke neoplasm subdural hematoma If not available a non contrast brain MRI or non contrast head CT must be done during Screening Living at the same home or residential assisted living facility for a minimum of 6 weeks before Screening Visit 1 Capable of self locomotion alone or with the aid of an assistive device and have an identified study partner who should have daily contact approximately 10 hours a week or more and is willing to Attend all visits and report on participant’s status Oversee participant compliance with medication and study procedures Participate in the study assessments and provide IC to participate in the study History of psychotic symptoms meeting International Psychogeriatric Association criteria for at least 2 months prior to Screening Visit 1 participants may or may not have symptoms of agitation CGI S scale with a score greater than or equal to 4 moderate at Screening Visit 1 and at Visit 2 CGI S requires the assessor to consider aspects of the psychosis hallucinations and delusions prior to providing a global assessment of severity AD participants are required to have NPI C H plus D score of greater than or equal to 6 AND meet at least one of the following criteria at Screening Visit 1 and Visit 2 Moderate to severe delusions defined as NPI C Delusions domain score of greater than or equal to 2 on 2 of the 8 items OR Moderate to severe hallucinations defined as NPI C Hallucinations domain score of greater than or equal to 2 on 2 of the 7 items MMSE score of 8 to 22 inclusive at Screening Visit 1 If the participant is taking a cholinesterase inhibitor and/or memantine they must have been on a stable dose for 6 weeks prior to Screening Visit 1 and willing to maintain a stable dose for the duration of the study Participant is willing and able to visit the clinic in an outpatient setting for the study duration, follow instructions, and comply with the protocol requirements BMI must be within 18 to 40 kg/m to the ratio 2 inclusive Female participants must not be pregnant or breastfeeding.
•Individuals of childbearing potential (IOCBP), or male particpants whose sexual partners are IOCBP, must be able and willing to use at least 1 highly effective method of contraception during the study and for at least 1 menstrual cycle (eg, 30 days) after the last dose of IMP.
•Sperm donation is not allowed for 30 days after the final dose of the IMP.
•A female participant is considered to be an IOCBP after menarche and until she is in a postmenopausal state for 12 months or otherwise permanently sterile (for which acceptable methods include hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).
•For the definition and list of highly effective methods of contraception.

排除标准

•Psychotic symptoms that are primarily attributable to a condition other than the AD causing the dementia eg schizophrenia schizoaffective disorder delusional disorder or mood disorder with psychotic features History of major depressive episode with psychotic features during the 12 months prior to Screening Visit 1 History of bipolar disorder schizophrenia or schizoaffective disorder Significant or severe medical conditions including pulmonary hepatic renal hematologic gastrointestinal endocrine immunologic dermatologic neurologic cardiovascular or oncologic disease or any other condition that in the opinion of the Investigator could jeopardize the safety of the participant ability to complete or comply with the study procedures or validity of the study results Participants with any grade of hepatic impairment mild Child-Pugh Class A moderate Child-Pugh Class B and severe Child-Pugh Class C will be excluded Significant and severe renal impairment based on a screening cutoff for estimated glomerular filtration rate of less than or equal to 50 mL per min History of ischemic stroke within 12 months prior to Screening Visit 1 or any evidence of hemorrhagic stroke History of cerebral amyloid angiopathy epilepsy CNS neoplasm current unstable thyroid function or unexplained syncope Any of the following New York Heart Association Class II or greater congestive heart failure Grade 2 or greater angina pectoris History of any of the following Sustained ventricular tachycardia Ventricular fibrillation Torsades de pointes Implantable cardiac defibrillator Myocardial infarction within the 6 months prior to Screening (Visit 1) Personal or family history of symptoms of long QT syndrome as evaluated by the Investigator Human immunodeficiency virus (HIV), cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections as indicated by medical history or LFT results History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma as evaluated by the Investigator Male participants are excluded from the study if any of the following criteria apply: i) History of bladder stones ii) History of recurrent urinary tract infections iii) Serum prostate specific antigen less than 10 ng/mL at Screening (Visit 1) iv) An IPSS score of 5 (almost always) on items 1, 3, 5, or 6 (see Section 9.4.13) v) A sum of scores on IPSS items 1, 3, 5, and 6 of greater than or equal to 9 History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months Risk of suicidal behavior during the study as determined by the Investigator’s clinical assessment and/or C-SSRS as confirmed by the following: i) Answers “Yes” on items 3, 4, or 5 (C-SSRS – ideation) with the most recent episode occurring within the 2 months before screening or, ii) Answers “Yes” to any of the 5 items (C-SSRS behavior) with an episode occurring within the 12 months before Screening Individuals who are breastfeeding Prior exposure to KarXT Unable to taper and discontinue a concomitant medication that would preclude participation in this study History of receiving monoamine oxidase inhibitors, anticonvulsants mood stabilizers (eg, lithium), tricyclic antidepressants (eg, imipramine, desipramine), or any other psychoactive medications except for as needed anxiolytics (eg, lorazepam) within 6 weeks prior to Screening (Visit 1) Experienced any significant AEs due to trospium, including a known hypersensitivity to trospium.