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

Alzheimer's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05602727
• Other study ID #: 1942-008
• Secondary ID: MK-1942-008jRCT2
• Status: Terminated
• Phase: Phase 2
• Start date: December 2, 2022
• Est. completion date: September 27, 2023

Study information

• Verified date: October 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 99
• Est. completion date: September 27, 2023
• Est. primary completion date: September 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Dementia

Intervention

Drug:
• MK-1942
MK-1942 oral capsule
• Placebo
Placebo oral capsule

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Canada,  Colombia,  Italy,  Japan,  Korea, Republic of,  New Zealand,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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

External Links

•   Merck Clinical Trials Information