Efficacy and Safety of MK-1942 as an Adjunct Therapy in Participants With Mild to Moderate Alzheimer's Disease Dementia (MK-1942-008)

A Phase 2a/2b Randomized, Placebo-Controlled Clinical Study To Evaluate The Safety And Efficacy Of MK-1942 As Adjunctive Therapy In Participants With Mild To Moderate Alzheimer's Disease Dementia

The main purpose of this study is to assess is to evaluate the safety and efficacy of MK-1942 as adjunctive therapy in participants with mild to moderate Alzheimer's Disease (AD) dementia.

Study Overview

• Status: Terminated
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: MK-1942; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@merck.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1012
    • IDIM - Instituto de Diagnóstico e Investigaciones Metabólicas ( Site 0204)
  • Buenos Aires, Argentina, C1427CCP
    • Instituto Geriatrico Nuestra Señora de Las Nieves ( Site 0208)
  • Buenos Aires, Argentina, C1428AQK
    • Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI) ( Site 0201)
  • Buenos Aires
    • Banfield, Buenos Aires, Argentina, 1828
      • Clinica Privada Banfield ( Site 0205)
  • Caba
    • Buenos Aires, Caba, Argentina, 1181
      • Hospital Italiano de Buenos Aires-Geriatrics ( Site 0210)
  • Cordoba
    • Córdoba, Cordoba, Argentina, X5004AOA
      • Instituto Kremer ( Site 0202)
• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2113
      • KARA Institute for Neurological Diseases ( Site 1902)
  • Victoria
    • Ivanhoe, Victoria, Australia, 3079
      • Austin Health-Medical & Cognitive Research Unit ( Site 1901)
    • Malvern, Victoria, Australia, 3144
      • HammondCare ( Site 1903)
• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1Z9
      • OCT Research ULC ( Site 0113)
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3S 1N2
      • Centricity Research - Halifax ( Site 0111)
  • Ontario
    • Ottawa, Ontario, Canada, K1Z1G3
      • Ottawa Memory Clinic ( Site 0105)
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre ( Site 0106)
    • Toronto, Ontario, Canada, M5T 2S8
      • Toronto Western Hospital-Memory clinic ( Site 0102)
  • Quebec
    • Gatineau, Quebec, Canada, J8T 8J1
      • Clinique de la Mémoire de l'Outaouais ( Site 0114)
• Colombia
  • Antioquia
    • Medellin, Antioquia, Colombia, 050012
      • Instituto Neurológico de Colombia ( Site 0415)
    • Medellin, Antioquia, Colombia
      • Grupo Neurociencias de Antioquia ( Site 0417)
  • Distrito Capital De Bogota
    • Bogotá, Distrito Capital De Bogota, Colombia, 111166
      • Centro de Investigaciones del Sistema Nervioso - Grupo Cisne ( Site 0414)
  • Valle Del Cauca
    • Cali, Valle Del Cauca, Colombia, 760032
      • Fundacion Valle del Lili- CIC ( Site 0418)
• Italy
  • Brescia, Italy, 25125
    • Centro S Giovanni Di Dio Fatebenefratelli ( Site 1205)
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore (
  • Lombardia
    • Milano, Lombardia, Italy, 20122
      • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico-UOSD Malattie Neurodegenerative ( Site 1204
    • Milano, Lombardia, Italy, 20132
      • Ospedale San Raffaele ( Site 1202)
    • Monza, Lombardia, Italy, 20900
      • Ospedale San Gerardo-ASST Monza-Dipartimento di Neuroscienze ( Site 1201)
• Japan
  • Kyoto, Japan, 606-0851
    • Ishikawa Clinic ( Site 2306)
  • Osaka, Japan, 5340021
    • Himuro Neurology Clinic ( Site 2304)
  • Hyogo
    • Kobe, Hyogo, Japan, 657-0825
      • Kakigi Cognition and Emotion Clinic of Hope ( Site 2307)
  • Kagawa
    • Kita-gun, Kagawa, Japan, 761-0793
      • Kagawa University Hospital ( Site 2308)
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 214-0014
      • Kishiro Mental Clinic ( Site 2310)
    • Saiwaiku,Kawasaki, Kanagawa, Japan, 212-0016
      • Kawasaki Saiwai Clinic ( Site 2302)
  • Osaka
    • Toyonaka, Osaka, Japan, 5600004
      • Nagomi Clinic ( Site 2305)
  • Tokyo
    • Itabashi, Tokyo, Japan, 173-0015
      • Tokyo Metropolitan Geriatric Hospital ( Site 2301)
• Korea, Republic of
  • Incheon, Korea, Republic of, 22332
    • Inha University Hospital ( Site 2104)
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center-Department of Neurology ( Site 2101)
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center ( Site 2102)
  • Seoul, Korea, Republic of, 07804
    • Ewha Womans University Seoul Hospital ( Site 2103)
• New Zealand
  • Canterbury
    • Christchurch, Canterbury, New Zealand, 8011
      • CGM Research Trust ( Site 2001)
• Spain
  • Barcelona, Spain, 08034
    • Fundació ACE ( Site 1604)
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos ( Site 1608)
  • Zaragoza, Spain, 50012
    • Hospital Viamed Montecanal-Neurociencia ( Site 1606)
  • Barcelona
    • Terrassa, Barcelona, Spain, 08222
      • Hospital Universitari Mutua Terrassa-Neurology ( Site 1607)
  • Cataluna
    • Barcelona, Cataluna, Spain, 08036
      • HOSPITAL CLÍNIC DE BARCELONA ( Site 1609)
    • Barcelona, Cataluna, Spain, 08041
      • Hospital de la Santa Creu i Sant Pau ( Site 1603)
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universidad de Navarra-Neurology ( Site 1602)
  • Pais Vasco
    • Getxo, Pais Vasco, Spain, 48993
      • Centro de Atención Especializada Oroitu ( Site 1610)
  • Valenciana, Comunitat
    • Valencia, Valenciana, Comunitat, Spain, 46017
      • Hospital Universitario Doctor Peset-Neurología ( Site 1601)
• United Kingdom
  • Birmingham, United Kingdom, B16 8LT
    • Re:Cognition Health - Birmingham ( Site 1801)
  • Plymouth, United Kingdom, PL6 8BT
    • Re:Cognition Health - Plymouth ( Site 1803)
  • Edinburgh, City Of
    • Edinburgh, Edinburgh, City Of, United Kingdom, EH12 9DQ
      • Brain Health Scotland Life Sciences ( Site 1810)
  • Glasgow City
    • Glasgow, Glasgow City, United Kingdom, G51 4TF
      • Queen Elizabeth University Hospital-Glasgow Clinical Research Facility ( Site 1808)
  • London, City Of
    • London, London, City Of, United Kingdom, W1G 9JF
      • Re:Cognition Health - London ( Site 1804)
  • Wiltshire
    • Swindon, Wiltshire, United Kingdom, SN3 6BW
      • Kingshill Research Centre ( Site 1807)
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Alzheimer's Institute ( Site 0017)
  • California
    • Fullerton, California, United States, 92835
      • Neurology Center of North Orange County ( Site 0039)
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Research, LLC ( Site 0058)
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research Institute ( Site 0013)
    • Hallandale Beach, Florida, United States, 33009
      • Velocity Clinical Research, Hallandale Beach ( Site 0025)
    • Maitland, Florida, United States, 32751
      • K2 Medical Research ( Site 0057)
    • Miami, Florida, United States, 33122
      • Premier Clinical Research Institute ( Site 0038)
    • Naples, Florida, United States, 34105
      • Collier Neurologic Specialists ( Site 0045)
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center for Medical Research ( Site 0044)
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta ( Site 0016)
  • Illinois
    • Elk Grove Village, Illinois, United States, 60007
      • Alexian Brothers Medical Center ( Site 0011)
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research ( Site 0055)
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Global Medical Institutes LLC; Princeton Medical Institute ( Site 0053)
    • Toms River, New Jersey, United States, 08755
      • Advanced Memory Research Institute of New Jersey ( Site 0027)
  • New York
    • Staten Island, New York, United States, 10314
      • Richmond Behavioral Associates ( Site 0008)
  • North Carolina
    • Matthews, North Carolina, United States, 28105
      • AMC Research, LLC ( Site 0004)
  • Ohio
    • Canton, Ohio, United States, 44718
      • NeuroScience Research Center ( Site 0009)
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Headlands ( Site 0018)
  • Texas
    • Wichita Falls, Texas, United States, 76309
      • Grayline Research Center ( Site 0003)
  • Vermont
    • Bennington, Vermont, United States, 05201
      • The Memory Clinic ( Site 0054)
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Re:Cognition Health ( Site 0031)
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center ( Site 0056)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has mild to moderate AD dementia based on the national institute of neurological and communicative diseases and stroke/Alzheimer's Disease and related disorders association (NINCDS-ADRDA) criteria.
• Has mini-mental state examination (MMSE) score between 12-22 (inclusive) at screening.
• Is using acetylcholinesterase inhibitors (AChEI) therapy for management of AD dementia at Screening and during the study. These medications must be at stable approved dose levels ≥3 months before the first dose of study intervention and the regimens must remain constant throughout the study to the extent that is clinically appropriate.
• Has a designated study partner who can fulfill the requirements of this study. The study partner will need to spend sufficient time with the participant to be familiar with their overall function and behavior and be able to provide adequate information about the participant needed for the study including, knowledge of functional and basic activities of daily life, work/educational history, cognitive performance, emotional/psychological state, and general health status.

Exclusion Criteria:

• Has a known history of stroke or cerebrovascular disease that is clinically important in the investigator's opinion.
• Has diagnosis of a clinically relevant central nervous system (CNS) disease other than AD dementia (with protocol-specified exceptions).
• Has a history of seizures or epilepsy within the 10 years preceding Screening.
• Has any other major CNS trauma, or infections that affect brain function.
• Has evidence of a clinically relevant or unstable psychiatric disorder, based on criteria from the diagnostic and statistical manual of mental disorders (fifth edition), including schizophrenia or other psychotic disorder, bipolar disorder, major depression, or delirium. Major depression in remission is not exclusionary.
• Has a severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or administration intervention.
• Has a history of malignancy occurring within the 5 years immediately before Screening, except for a participant who has been adequately treated for 1 or more of the following: basal cell or squamous cell skin cancer; in situ cervical cancer; localized prostate carcinoma; who has undergone potentially curative therapy with no evidence of recurrence for ≥3 years post-therapy, and who is deemed to be at low risk for recurrence.
• Has a risk factor for QTc prolongation.
• Has a history of alcoholism or drug dependency/abuse within the 5 years preceding screening.
• Has a known allergy or intolerance to the active or inert ingredients in MK-1942.
• Has received any anti-amyloid agents or antibodies, or any of the following medications: CNS-penetrant anticholinergics, neuroleptics, anticonvulsants, narcotics, glutamatergic agents, agents with possible psychotropic effects, and experimental acute respiratory syndrome coronavirus 2 (COVID-19) therapies.
• Has liver disease, including but not limited to chronic viral hepatitis, non viral hepatitis, cirrhosis, malignancies, autoimmune liver diseases.
• Has an abnormal thyroid-stimulating hormone (TSH) value if confirmed by abnormal T4 value.
• Resides in a nursing home or assisted care facility with need for direct continuous medical care and nursing supervision. Participant may reside in such facilities provided continuous direct medical care is not required and a qualified study partner is available for coparticipation and the participant is physically able to attend all required study visits.
• Had major surgical procedure or donated or lost >1 unit of blood (approximately 500 mL) within the 4 weeks before screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MK-1942 5 mg; Participants will receive a single 5 mg MK-1942 capsule twice daily (BID), taken orally for 12 weeks. A mock titration will be done to maintain the study blind despite no changes in dose.	Drug: MK-1942; MK-1942 oral capsule
Experimental: MK-1942 15 mg; Participants will receive a single 8 mg MK-1942 capsule twice daily (BID), taken orally for one week. Then the dose is titrated up to 15 mg MK-1942 capsule twice daily (BID), taken orally for up to 11 weeks.	Drug: MK-1942; MK-1942 oral capsule
Placebo Comparator: Placebo; Participants will receive a placebo capsule twice daily (BID), taken orally for 12 weeks. A mock titration will be done to maintain the study blind despite no changes in dose.	Drug: Placebo; Placebo oral capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in the Alzheimer's Disease Assessment Scale-11-item Cognitive Subscale (ADAS-Cog11) Score at Week 12	Mean change from baseline at week 12 is assessed for ADAS-Cog11 score. The ADAS-Cog11 is a structured scale that evaluates memory, orientation, attention, reasoning, language, and constructional praxis. ADAS-Cog11 measures cognition by assessing 11 metrics impaired in AD: word recall; commands; constructional praxis; naming objects and fingers; ideational praxis; orientation; word recognition; remembering test instructions; spoken language ability; word-finding difficulty; and comprehension of spoken language. Higher scores indicate greater impairment.	Baseline and Week 12
Number of Participants Experiencing an Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to ~ 14 Weeks
Number of Participants Discontinuing Study Medication due to an Adverse Event	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to ~ 12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alzheimer's Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC) Overall Score at Week 12	ADCS-CGIC scores are assessed at week 12. The ADCS-CGIC is a global scale assessing cognition and function based on structured interviews of both the participant and study partner. The ADCS-CGIC focuses on clinicians' observations of change in the patient's cognitive, functional, and behavioral performance since the beginning of the study. Improvement in the ADCS-CGIC overall score, with a score of 1, 2, or 3 indicates improvement. The ADCS-CGIC is a clinician-rated measure of: global severity at baseline scored from 1 (normal, not at all ill) to 7 (among the most extremely ill patients); and global change at follow-up scored from 1 (marked improvement) to 7 (marked worsening), where 4 indicates no change.	Week 12
Mean Change From Baseline in The Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Total Score at Week 12	Mean change from baseline at week 12 is assessed for ADCS-ADL score. The ADCS-ADL is an informant-based measure of the patient's functional ability in activities of daily living (ADL). The ADCS-ADL assesses the competence of participants with AD dementia in basic and instrumental ADLs. The ADCS-ADL is a 23 item scale that includes 6 basic ADL tems and 17 instrumental ADL items that provide a total score from 0-78, with a lower score indicating greater severity.	Baseline and Week 12

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2022
• Primary Completion (Actual): September 27, 2023
• Study Completion (Actual): September 27, 2023

Study Registration Dates

• First Submitted: October 27, 2022
• First Submitted That Met QC Criteria: October 27, 2022
• First Posted (Actual): November 2, 2022

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 20, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Alzheimer's Disease
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Tauopathies; Dementia; Alzheimer Disease
• Other Study ID Numbers: 1942-008; MK-1942-008 (Other Identifier: Merck Protocol Number); 2021-006336-94 (EudraCT Number); jRCT2031220532 (Registry Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No