Study to Evaluate the Efficacy and Safety of KDS2010 in Patients With Alzheimer's Disease With Mild Cognitive Impairment and Mild Dementia Due to Alzheimer's Disease

NCT07027072 | Recruiting Phase 2

• 2 other identifiers: NB_KDS_ADP2_23KCT0010589
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 8

Brief Summary

A randomized, double-blind, placebo-controlled, dose-finding Phase 2a clinical trial will be conducted to evaluate the efficacy and safety of KDS2010 in patients with Mild Cognitive Impairment (MCI) due to Alzheimer's disease (AD) and mild dementia due to Alzheimer's disease. Based on preliminary efficacy observed in the Phase 1 clinical trial, a multinational study will be conducted in both Korea and the United States. Eligible patients diagnosed with MCI or mild Alzheimer's disease will be stratified by disease stage (MCI/mild AD) and geographic region (Korea/USA) prior to randomization. Subjects will be randomly assigned in a 1:1:1 ratio to either Treatment Group 1, Treatment Group 2, or the Control Group. The investigational product will be administered orally once daily for a duration of 24 weeks. Approximately 114 subjects will be enrolled, including an estimated 20% dropout rate, with 38 subjects assigned to each group (Treatment Group 1, Treatment Group 2, and Control Group). The objectives of the study are as follows:

1. 1.Efficacy Objectives: Efficacy will be evaluated through changes in cognitive function, self-management, and daily living activities before and after administration of KDS2010. Biomarker analysis in plasma and in cerebrospinal fluid (CSF; optional) will also be conducted to explore treatment efficacy.
2. 2.Safety Objectives: The safety and tolerability will be evaluated after administration of KDS2010.
3. 3.Exploratory Objectives: The efficacy of Treatment Groups 1 and 2 compared to the Control group will be explored through cognitive endpoints (the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13), and the Mini-Mental State Examination (MMSE)), stratified by demographic information, tauopathy, and ApoE4 genes.

Conditions

Mild Cognitive Impairment (MCI); Mild Dementia; Alzheimer's Disease

Keywords

Mild Cognitive Impairment; Mild Dementia; KDS2010; MAO-B inhibitor; Alzheimer's Disease

Outcome Measures

Primary Outcomes (5)

• Change from Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) score

  Clinical Dementia Rating (CDR) is a tool developed to assess the clinical stages of Alzheimer's disease. CDR 0 indicates "no dementia," CDR 0.5 "questionable," CDR 1 "mild," CDR 2 "moderate," and CDR 3 "severe" dementia. The range for CDR-SB is 0 to 18 points, where higher scores indicate more severe dementia.

  Screening (-8 Week~), Week 4, Week 8, Week 12, Week 24, Week 26

• Time to ≥0.5-point increase in CDR-SB

  Time from randomization to the first occurrence of ≥0.5-point increase in CDR-SB score.

  Up to Week 26

• Change from Baseline in Mini-Mental State Examination (MMSE) score

  The MMSE is a cognitive function and disease severity assessment composed of 30 items. Each is graded on a 2-point scale where 1 point is awarded for correct performance and 0 points if not performed correctly. Lower total scores on the MMSE indicate cognitive impairment.

  Screening (-8 Week~), Week 12, Week 24, Week 26

• Change from Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) score

  ADAS-Cog13 is a comprehensive tool for the early diagnosis of dementia and the sensitive assessment of disease progression stages. The assessment includes 9 "neuropsychological tests" and 4 "clinical assessments of cognitive damage", totaling 13 items. The higher the total score of the ADAS-Cog, the more it indicates cognitive dysfunction.

  Screening (-8 Week~), Week 12, Week 24, Week 26

• Change from Baseline in Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q-SV) score

  The A-IADL-Q is a questionnaire designed to assess impairments in instrumental activities of daily living (IADL) in patients with dementia. The A-IADL-Q-SV is a short version of the A-IADL-Q, consisting of 30 items that assess instrumental daily functioning sensitive to cognitive decline. Each item is rated on a 5-point Likert scale, with higher scores indicating better functional ability.

  Screening (-8 Week~), Week 12, Week 24

Secondary Outcomes (2)

• Percentage change from Baseline in plasma and Cerebrospinal Fluid(CSF) biomarkers

  Screening (-8 Week~), Week 12, Week 24

• Percentage change from Baseline in plasma Monoamine Oxidase B (MAO-B) specific activity

  Screening (-8 Week~), Week 26

Other Outcomes (13)

• Number of subjects with treatment-related Adverse Events (AEs)

  Through study completion (approx. 26 weeks)

• Change from baseline in systolic and diastolic blood pressure

  Screening (-8 Week~), Baseline (Week 0), Week 4, Week 8, Week 12, Week 24, Week 26

• Change from baseline in pulse rate

  Screening (-8 Week~), Baseline (Week 0), Week 4, Week 8, Week 12, Week 24, Week 26

Study Arms (3)

Control Group_Placebo

PLACEBO COMPARATOR

A placebo will be administered orally once daily as two tablets per day for 24 weeks. This group will match the investigational drug in appearance but contain no active ingredients to maintain blinding.

Drug: Placebo

Treatment Group 1_KDS2010 60 mg

EXPERIMENTAL

KDS2010 60 mg will be administered orally once daily as two tablets per day (one 60 mg KDS2010 tablet and one placebo tablet, 60 mg total) for 24 weeks. This group will receive the active investigational drug to evaluate its safety and efficacy.

Drug: KDS2010

Treatment Group 2_KDS2010 120 mg

EXPERIMENTAL

KDS2010 60 mg will be administered orally once daily as two tablets per day (two 60 mg KDS2010 tablets, 120 mg total) for 24 weeks. This group will receive the higher dose of the investigational drug to evaluate its safety and efficacy.

Drug: KDS2010

Interventions

KDS2010 DRUG

KDS2010 will be administered orally once daily, two tablets per day, for 24 weeks. Dosage will be either 60 mg or 120 mg depending on the assigned group.

Treatment Group 1_KDS2010 60 mg; Treatment Group 2_KDS2010 120 mg

Placebo DRUG

Placebo matching the investigational product in appearance but containing no active ingredient, administered orally once daily, two tablets per day, for 24 weeks.

Control Group_Placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female adults aged ≥50 and ≤85 years at the time of written consent
• Patients with MCI or mild AD confirmed at screening according to the 2024 diagnostic criteria (APPENDIX 1) of the National Institute on Aging-Alzheimer's Association (NIA-AA)
• Subjects whose total CDR score (CDR-GS) is 0.5 to 1.0 at screening (however, CDR memory score is ≥0.5)
• Subjects with a Mini-Mental State Examination (MMSE) score of 21 to 30 at screening
• Subjects who test positive for amyloid on Positron Emission Tomography (PET) during screening
• Subjects who have a caregiver capable of providing accurate information about the subject's cognitive and functional abilities and appropriate for the planned assessments in the study, as judged by the investigator
• Subjects (or their legal representatives) who have voluntarily agreed to participate in this study and have given written consent

You may not qualify if:

• Cognitive impairment or dementia due to causes other than Alzheimer's disease
• Vascular dementia, central nervous system infections (e.g., HIV, syphilis, etc.), head trauma, Creutzfeldt-Jakob disease, Pick's disease, Huntington's disease, Parkinson's disease, subdural hematoma, normal pressure hydrocephalus, brain tumor, thyroid disorders, parathyroid disorders, Vitamin B12 deficiency, folic acid deficiency, other metabolic and nutritional deficiencies, etc.
• Alcohol or drug abuse, dependence
• Subjects with cognitive impairment due to hypothyroidism, nutritional deficiencies, Vitamin B12 or folic acid deficiency as assessed during screening
• Subjects confirmed during screening to have had the following medical history:
• Malignant tumors within five years prior to screening except for basal cell carcinoma, cutaneous squamous cell carcinoma, thyroid cancer, or carcinoma in situ that has not recurred in over three years and is considered successfully treated by the investigator
• History of alcohol or drug abuse within two years prior to screening
• Loss of consciousness of unknown cause, or seizure within the past 52 weeks before screening
• Unstable and clinically significant cardiovascular diseases despite appropriate treatment (acute coronary syndrome (ACS), tachycardia, clinically significant arrhythmias, cardiomyopathy, angina of at least CSS III, heart failure of NYHA II-IV, or clinically significant valvular heart disease) within 24 weeks before baseline
• Severe or active infectious diseases requiring antibiotics or antivirals within four weeks before baseline
• A history of stroke involving a major vascular area, transient ischemic attack (TIA), epilepsy, or severe head trauma with loss of consciousness
• Hypersensitivity or allergy to any components of the investigational product
• Subjects confirmed during screening to have had the following accompanying disease:
• Clinically significant neurological diseases or serious pathological findings affecting cognitive function as confirmed by brain imaging studies within 52 weeks prior to screening, including multiple sclerosis, normal pressure hydrocephalus, brain tumor (however, exceptions are allowed for lesions diagnosed as benign and with a maximum diameter of less than 1 cm), spinal cord infarction, major hemorrhage (defined as having a diameter \> 1 cm in MRI) or subdural hemorrhage, cerebral vascular malformation, communicating hydrocephalus, inflammatory demyelinating diseases, etc.
• Uncontrolled hypertension despite appropriate treatment at screening or baseline (SBP ≥160 mmHg or DBP ≥100 mmHg)

Sponsors & Collaborators

• NeuroBiogen Co., Ltd: lead

Study Sites (8)

Chonnam National Unversity Hospital

Gwangju, Gwangju, 61469, South Korea

RECRUITING

Hanyang University Guri Hospital

Guri-si, Gyeonggi-do, 11923, South Korea

RECRUITING

The Catholic University of Korea St. Vincent's Hospital

Suwon, Gyeonggi-do, 16247, South Korea

RECRUITING

Ajou University Hospital

Suwon, Gyeonggi-do, 16499, South Korea

RECRUITING

Gachon University Gil Medical Center

Incheon, Incheon, 21565, South Korea

RECRUITING

Hanyang University Seoul Hospital

Seoul, Seoul, 04763, South Korea

RECRUITING

Konkuk University Medical Center

Seoul, Seoul, 05030, South Korea

RECRUITING

Asan Medical Center

Seoul, Seoul, 05505, South Korea

RECRUITING

MeSH Terms

Conditions

Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Sangwook Kim, Chief Executive Officer

  NeuroBiogen Co., Ltd

  STUDY DIRECTOR

Central Study Contacts

Yeonsil Moon, Professor

CONTACT

+82)70-4018-8009; neuro_reply@neurobiogen.com

Dayoung Kim, Professor

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: A double-blind design is used to ensure scientific validity. Subjects and investigators are unaware of treatment allocation, with identical appearance between the drug and placebo. Randomization numbers are used for subject identification, and group assignments are disclosed only after the end of treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, Double-Blind, Placebo-Controlled, Dose-Finding, Phase 2a Clinical Trial

Study Record Dates

• First Submitted: May 15, 2025
• First Posted: June 18, 2025
• Study Start: August 6, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: August 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

KR (8)