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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

14 Feb 2023 → 10 Aug 2023

Decision date (initial)

2023-07-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-504017-79-00

EudraCT number

2021-006336-94

WHO UTN

U1111-1288-7166

ClinicalTrials.gov

NCT05602727

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenetic, Pharmacokinetic, Therapy, Pharmacogenomic, Dose response, Safety

1. To assess the efficacy of MK-1942 at 5 mg and 15 mg bid as adjunctive therapy on the ADAS-Cog11 score compared with placebo at Week 12.
2. To evaluate the safety and tolerability of MK-1942 as adjunctive therapy.

Secondary objectives 2

1. To assess the efficacy of MK-1942 at 5 mg and 15 mg bid as adjunctive therapy on the ADCS-CGIC Overall score compared with placebo at Week 12.
2. To assess the efficacy of MK-1942 at 5 mg and 15 mg bid as adjunctive therapy on the ADCS-ADL Total score as compared with placebo at Week 12.

Conditions and MedDRA coding

Treatment of AD dementia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

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.

Exclusion criteria 15

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 of 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Change from baseline in the Alzheimer’s Disease Assessment Scale-11-item cognitive subscale (ADAS-Cog11) score at Week 12
2. Number of Participants Experiencing Adverse Events (AEs)
3. Number of Participants Discontinuing Study Intervention Due to AEs

Secondary endpoints 2

1. Alzheimer’s Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC) Overall score at Week 12
2. Change from baseline in the Alzheimer’s Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Total score at Week 12

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Aristide Merola

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Aristide Merola

Third parties 6

Locations

2 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications