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 clinical trial will be conducted in Korea. Eligible patients diagnosed with MCI or mild Alzheimer's disease will be stratified by disease stage (MCI/mild AD) 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. 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. Safety Objectives: The safety and tolerability will be evaluated after administration of KDS2010. 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.
Based on nonclinical and Phase 1 clinical data, KDS2010 will be administered orally once daily at two dose levels: 60 mg and 120 mg.
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
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
Parallel
KDS2010
DrugKDS2010 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.
Placebo
DrugPlacebo matching the investigational product in appearance but containing no active ingredient, administered orally once daily, two tablets per day, for 24 weeks.
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.
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.
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.
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.
Percentage change from Baseline in plasma and Cerebrospinal Fluid(CSF) biomarkers
Changes in plasma and CSF levels of MAO-B (Monoamine Oxidase B) specific activity, GFAP (Glial Fibrillary Acidic Protein), P-tau181 (Phosphorylated-Tau 181), P-tau217 (Phosphorylated-Tau 217), Aβ-40 (Amyloid beta 40), Aβ-42 (Amyloid beta 42), NfL (Neurofilament Light Chain), BDNF (Brain-derived Neurotrophic Factor), IL-1β (Interleukin-1β), and TNF-α (Tumor Necrosis Factor-α).
Percentage change from Baseline in plasma Monoamine Oxidase B (MAO-B) specific activity
Plasma MAO-B specific activity at Week 26 compared to baseline.
Number of subjects with treatment-related Adverse Events (AEs)
AEs will be coded using MedDRA and assessed for severity and causality using CTCAE v5.0. The number of subjects affected and the incidence rates will be presented for each treatment group.
Change from baseline in systolic and diastolic blood pressure
Blood pressure will be measured in mmHg at each visit.
Change from baseline in pulse rate
Pulse rate will be measured in beats per minute.
Change from baseline in body temperature
Body temperature will be measured using a standard thermometer.
Click on the lead sponsor to view all of their trials.
