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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

Phase 2a/2b Study of MK-1942 in Participants with Alzheimer's Disease dementia

99

MK-1942 5 mg group -Mean Age: 74.1 years -Sex: Female 71.4%, Male 28.6% -Ethnicity: Hispanic or Latino 5.7%, Not Hispanic or Latino 94.3% -Race: Asian 17.1%, Black or African American 0.0%, White 82.9% MK-1942 15 mg group -Mean Age: 74.7 years -Sex: Female 67.7%, Male 32.3% -Ethnicity: Hispanic or Latino 19.4%, Not Hispanic or Latino 80.6% -Race: Asian 9.7%, Black or African American 0.0%, White 90.3% Placebo group -Mean Age: 72.3 years -Sex: Female 69.7%, Male 30.3% -Ethnicity: Hispanic or Latino 6.1%, Not Hispanic or Latino 93.9% -Race: Asian 18.2%, Black or African American 3.0%, White 78.8% Total -Mean Age: 73.7 years -Sex: Female 69.7%, Male 30.3% -Ethnicity: Hispanic or Latino 10.1%, Not Hispanic or Latino 89.9% -Race: Asian 15.2%, Black or African American 1.0%, White 83.8%

MK-1942 5 mg group -Randomized: 35 participants -Completed the study: 13 participants -Discontinued the study: 22 participants (including 1 participant randomized by mistake without study medication, 18 participants who discontinued due to study termination by sponsor, 2 participants who discontinued due to withdrawal by subject, 1 participant who discontinued due to various reasons) MK-1942 15 mg group -Randomized: 31 participants -Completed the study: 8 participants -Discontinued the study: 23 participants (including 1 participant who discontinued due to physician decision, 15 participants who discontinued due to study termination by sponsor, 1 participant who discontinued due to withdrawal by subject, 6 participants who discontinued due to various reasons) Placebo group -Randomized: 33 participants -Completed the study: 12 participants -Discontinued the study: 21 participants (including 19 participants who discontinued due to study termination by sponsor, 1 participant who discontinued due to withdrawal by subject, 1 participant who discontinued due to various reasons)

Percentage of all-cause mortality -MK-1942 5 mg group: 0.00% (0/34 participants) -MK-1942 15 mg group: 0.00% (0/31 participants) -Placebo group: 0.00% (0/33 participants) Percentage of participants with serious adverse events -MK-1942 5 mg group: 2.94% (1/34 participant) -MK-1942 15 mg group: 6.45% (2/31 participants) -Placebo group: 6.06% (2/33 participants) Serious adverse events -MK-1942 5 mg group: Hemiparesis (1/34 participant [2.94%]) -MK-1942 15 mg group: Chest pain, Fall (1/31 participant [3.23%] each) -Placebo group: Bradycardia, Asthenia, Syncope (1/33 participant [3.03%] each) Percentage of participants with non-serious adverse events with an incidence of >5% in one or more treatment groups -MK-1942 5 mg group: 47.06% (16/34 participants) -MK-1942 15 mg group: 51.61% (16/31 participants) -Placebo group: 36.36% (12/33 participants) Non-serious adverse events with an incidence of >=5% -MK-1942 5 mg group: Alanine aminotransferase increased (29.41%), Dizziness (11.76%), Diarrhoea (8.82%), Fall (8.82%), Headache (8.82%), Abdominal pain (5.88%), Feeling abnormal (5.88%) -MK-1942 15 mg group: Nausea (16.13%), Alanine aminotransferase increased (16.13%), Dizziness (16.13%), Vomiting (9.68%), Fatigue (6.45%), Accidental overdose (6.45%), Aspartate aminotransferase increased (6.45%), Hypertension (6.45%) -Placebo group: Fall (12.12%), Dizziness (12.12%), COVID-19 (6.06%), Arthralgia (6.06%)

Primary Outcome Efficacy Change from baseline in the Alzheimer's Disease Assessment Scale-11-item Cognitive Subscale (ADAS-Cog11) score at Week 12 -Analysis population: Randomized participants who received at least 1 dose of study treatment, and who have baseline and a post-baseline assessment available, are included. A mixed-model repeated measures analysis of covariance was used in which partial data from participants not completing the study was utilized. -MK-1942 5 mg group: Least Squares Mean 2.9 (95% confidence interval [CI]: 0.7, 5.1) -MK-1942 15 mg group: Least Squares Mean -0.6 (95% CI: -3.0, 1.8) -Placebo group: Least Squares Mean 0.8 (95% CI: -1.4, 3.0) -Difference in Least Squares Means (MK-1942 5 mg - Placebo): 2.1 (97.5% CI: -1.6, 5.8), P-Value: 0.186 -Difference in Least Squares Means (MK-1942 15 mg - Placebo): -1.4 (97.5% CI: -5.2, 2.4), P-Value: 0.400 Safety Percentage of participants experiencing an adverse event (AE) -Analysis population: All randomized participants who received at least 1 dose of study treatment are included. -MK-1942 5 mg group: 50.0% (17/34 participants) -MK-1942 15 mg group: 67.7% (21/31 participants) -Placebo group: 54.5% (18/33 participants) Percentage of participants discontinuing study medication due to an AE -Analysis population: All randomized participants who received at least 1 dose of study treatment are included. -MK-1942 5 mg group: 11.8% (4/34 participants) -MK-1942 15 mg group: 19.4% (6/31 participants) -Placebo group: 9.1% (3/33 participants) Secondary Outcome Efficacy Alzheimer's Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC) overall score at Week 12 -Analysis population: Randomized participants who received at least 1 dose of study treatment, and who have the relevant assessment available, are included. -MK-1942 5 mg group: Mean 5.4 (Standard Deviation: 0.7) -MK-1942 15 mg group: Mean 5.8 (Standard Deviation: 0.9) -Placebo group: Mean 5.3 (Standard Deviation: 0.8) Change from baseline in the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) total score at Week 12 -Analysis population: Randomized participants who received at least 1 dose of study treatment, and who have baseline and a post-baseline assessment available, are included. A mixed-model repeated measures analysis of covariance was used in which partial data from participants not completing the study was utilized. -MK-1942 5 mg group: Least Squares Mean -1.7 (95% CI: -4.8, 1.4) -MK-1942 15 mg group: Least Squares Mean -3.0 (95% CI: -6.4, 0.4) -Placebo group: Least Squares Mean 1.2 (95% CI: -2.0, 4.4) -Difference in Least Squares Means (MK-1942 5 mg - Placebo): -2.9 (97.5% CI: -8.0, 2.2), P-Value: 0.196 -Difference in Least Squares Means (MK-1942 15 mg - Placebo): -4.2 (97.5% CI: -9.6, 1.3), P-Value: 0.081

Efficacy MK-1942 administered bid for 12 weeks as adjunctive therapy in participants with mild to moderate AD dementia did not show statistically significant differences compared with placebo in changes from baseline in ADAS-Cog11, ADCS-CGIC, or ADCS-ADL score. Safety No deaths were reported in the study. Higher incidences of elevated ALT or AST were reported in the MK-1942 intervention groups than in the placebo group.

Yes

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

https://jrct.mhlw.go.jp/latest-detail/jRCT2031220532

Tanaka Yoshiyuki

MSD K.K.

KITANOMARU SQUARE,1-13-12,Kudan-kita,Chiyoda-ku,Tokyo 102-8667,Japan

msdjrct@msd.com

MSDJRCT inquiry mailbox

MSD K.K.

KITANOMARU SQUARE,1-13-12,Kudan-kita,Chiyoda-ku,Tokyo 102-8667,Japan

+81-3-6272-1957

msdjrct@msd.com

Complete

Dec. 24, 2022

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

1) 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.
2) Has mini-mental state examination (MMSE) score between 12-22 (inclusive) at screening.
3) 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.
4) 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.

1) Has a known history of stroke or cerebrovascular disease that is clinically important in the investigator's opinion.
2) Has diagnosis of a clinically relevant central nervous system (CNS) disease other than AD dementia (with protocol-specified exceptions).
3) Has a history of seizures or epilepsy within the 10 years preceding Screening.
4) Has any other major CNS trauma, or infections that affect brain function.
5) 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.
6) 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.
7) 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.
8) Has a risk factor for QTc prolongation.
9) Has a history of alcoholism or drug dependency/abuse within the 5 years preceding screening.
10) Has a known allergy or intolerance to the active or inert ingredients in MK-1942.
11) 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.
12) Has liver disease, including but not limited to chronic viral hepatitis, non viral hepatitis, cirrhosis, malignancies, autoimmune liver diseases.
13) Has an abnormal thyroid-stimulating hormone (TSH) value if confirmed by abnormal T4 value.
14) 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.
15) Had major surgical procedure or donated or lost >1 unit of blood (approximately 500 mL) within the 4 weeks before screening.

Both

Alzheimer's Disease Dementia

MK-1942 5 mg bid, MK-1942 15 mg bid (8 mg bid for 1 week, and up-titrated to 15 mg bid), or placebo bid will be administered orally for 12 weeks.

- Change from baseline in the ADAS-Cog11 score at Week 12
- AEs
- Discontinuation of study intervention due to AEs

- ADCS-CGIC Overall Score at Week 12
- Change from baseline in the ADCS-ADL total score at Week 12

+81-3-3881-6116

Nov. 17, 2022

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