KDS2010 for people with MCI or mild dementia due to Alzheimer's disease.

A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding, Phase 2a Clinical Trial 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

This trial will test whether taking KDS2010 once daily for 24 weeks helps thinking and memory and is safe in people aged 50–85 who are amyloid-positive with MCI or mild Alzheimer's dementia.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 114 (estimated)
• Ages: 50 Years to 85 Years
• Sex: All
• Sponsor: NeuroBiogen Co., Ltd (Industry-sponsored)
• Drugs / interventions: aducanumab, lecanemab, donanemab, gantenerumab, solanezumab
• Locations: 8 sites (Gwangju, Gwangju and 7 other locations)
• Trial ID: NCT07027072 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled, dose-finding Phase 2a trial testing two doses of oral KDS2010 versus placebo over 24 weeks in about 114 participants. Eligible participants are aged 50–85, amyloid-positive by PET, and have MCI or mild dementia (CDR 0.5–1.0, MMSE 21–30); subjects are stratified by disease stage and geographic region before randomization. Participants are randomized 1:1:1 to two active dose groups or placebo, with safety, pharmacokinetics, and change in cognitive measures (primary efficacy) tracked through scheduled visits. The multinational trial enrolls at selected sites in Korea and the United States and allows for an estimated 20% dropout rate.

Who should consider this trial

Good fit: Ideal candidates are adults 50–85 who are amyloid-positive with MCI or mild Alzheimer's dementia (CDR 0.5–1.0, MMSE 21–30) and who have a caregiver able to support study participation.

Not a fit: Patients with moderate or severe dementia, cognitive impairment from non-Alzheimer's causes, major uncontrolled medical conditions, or recent use of AD-modifying or CNS-active drugs are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, KDS2010 could slow cognitive decline or improve symptoms in early-stage Alzheimer's disease and offer a new oral MAO-B inhibitor option with an acceptable safety profile.

How similar studies have performed: MAO-B inhibitors have been studied previously with mixed results for Alzheimer's symptoms, and KDS2010 showed preliminary efficacy in Phase 1, but larger randomized trials are needed to confirm benefit.

Eligibility criteria

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)
  * Dizziness or fainting when standing due to orthostatic hypotension that may affect the evaluation according to the judgment of the investigator
  * Uncontrolled diabetes (HbA1c \> 9%) during screening, despite appropriate treatment
  * Bleeding disorders (Platelet \<50,000/mm³) during screening, despite appropriate treatment
  * Patients with severe hepatic impairment (Child-pugh class C) at screening
  * Following laboratory test values at screening:

    * AST or ALT \> 2.5 x ULN
    * total bilirubin \> 1.5 x ULN (however, in case of Gilbert syndrome, \> 3.0 mg/dL)
    * MDRD eGFR \< 30 mL/min/1.73 m²
  * QTcF interval \>450 msecs (12-lead ECG) during screening
  * Gastrointestinal diseases that may affect oral administration or absorption (celiac disease, Crohn's disease, intestinal resection, etc.)
  * Gastrointestinal diseases, including gastric and duodenal ulcers, that may affect the safety evaluation according to the judgment of the investigator
  * Psychiatric diagnosis or symptoms that may interfere with the study (uncontrolled major depression, uncontrolled schizophrenia, uncontrolled bipolar affective disorder, etc.), as assessed by the investigator
  * Positive responses to items 4 or 5 on the Columbia University Suicide Severity Rating Scale (C-SSRS) during screening
  * Other conditions deemed by the investigator to potentially affect the outcome of the study
* Subjects who have undergone or require treatment with the following:

  * AD disease-modifying agents (aducanumab, lecanemab, donanemab, gantenerumab, solanezumab, blarcamesine, simufilam, tricaprilin, valiltramiprosate, etc.) within 12 weeks before screening
  * Medications that may improve cognitive abilities or affect AD treatment (AChEIs, donepezil, galantamine, rivastigmine, tacrine, memantine, etc.) within 12 weeks before screening, except if the subject has been on a stable dose for at least 12 weeks before baseline and maintains the same composition/dosage/method of administration during the study period
  * CNS-active drugs or those affecting cognitive function antidepressants other than serotonergic drugs \[e.g., bupropion\], sedatives \[e.g., carbamazepine\], dopamine antagonists \[e.g., antipsychotics, metoclopramide\], amfepramone, mazindol) within 12 weeks before screening
  * Central anticholinergics and sedating H1-antihistamines within 12 weeks before screening.

However, exceptions are allowed for one-time use of the drugs, such as second-generation H1 antihistamines (e.g., cetirizine, levocetirizine, etc.) or peripheral anticholinergics with no central action (e.g., trospium for treating overactive bladder). But the use is prohibited for at least 3 days from the date of cognitive function evaluation.

* Other investigational products or clinical trial devices within four weeks before baseline or five times the half-life of the drug (whichever is longer, and patients can be enrolled after wash-out)
* Monoamine oxidase inhibitors (MAOIs) and linezolid within two weeks before baseline or five times the half-life of the drug (whichever is longer, and patients can be enrolled after wash-out)
* Opioids (pethidine, tramadol, tapentadol, etc.) within two weeks before baseline or five times the half-life of the drug (whichever is longer, and patients can be enrolled after wash-out)
* Cyclobenzaprine and St. John's wort within two weeks before baseline or five times the half-life of the drug (whichever is longer, and patients can be enrolled after wash-out)
* The following serotonergic drugs within two weeks before baseline or five times the half-life of the drug (whichever is longer, and patients can be enrolled after wash-out),

  * selective serotonin (5HT1) agonists
  * lithium
  * lamotrigine
  * ritonavir
  * dapoxetine
  * Selective serotonin reuptake inhibitors (SSRIs)
  * dapoxetine
  * Serotonin-norepinephrine reuptake inhibitors (SNRIs)
  * Tricyclic or tetracyclic antidepressants
  * triazolopyridine antidepressant However, amitriptyline ≤ 50 mg/day, trazodone ≤ 100 mg/day, citalopram ≤ 20 mg/day, and sertraline ≤ 100 mg/day are allowed without washout.
* Use of sympathomimetics (ephedrine, methylphenidate, amphetamine, methamphetamine, lisdexamfetamine, etc.) during the screening period
* Use of Dextromethorphan during the screening period
* Use of CYP3A4 strong inducer, CYP3A4 strong inhibitor, CYP2D6 strong inducer, and CYP2D6 strong inhibitor during the screening period

  * Inability to undergo MRI or PET scans
  * Pregnant or breastfeeding women
  * Fertile women or men who are unwilling to use effective contraception\* from the date of written consent until 12 weeks after the last administration of the investigational product

    \*Effective contraception is defined as follows, and at least one method should be used:
    * Hormonal contraception (oral, injectable, implantable, etc.)
    * Intrauterine device (IUD) or system (IUS)
    * Sterilization or surgical procedures (vasectomy, bilateral tubal ligation/surgery, hysterectomy)
    * Dual contraception methods: Simultaneous use of barrier methods (male condoms) with the methods listed above
    * Absolute abstinence: Total abstinence from sexual intercourse is recognized if the investigator deems the subject's age, occupation, lifestyle, or sexual orientation assures contraception. However, periodic abstinence (calendar method, mucus method, and symptothermal method), withdrawal, and coitus interruptus are not recognized as effective contraception methods.
  * Other conditions deemed by the investigator to be unsuitable for participation in the study

Where this trial is running

Gwangju, Gwangju and 7 other locations

• Chonnam National Unversity Hospital — Gwangju, Gwangju, South Korea (Recruiting)
• Hanyang University Guri Hospital — Guri-si, Gyeonggi-do, South Korea (Recruiting)
• The Catholic University of Korea St. Vincent's Hospital — Suwon, Gyeonggi-do, South Korea (Recruiting)
• Ajou University Hospital — Suwon, Gyeonggi-do, South Korea (Recruiting)
• Gachon University Gil Medical Center — Incheon, Incheon, South Korea (Recruiting)
• Hanyang University Seoul Hospital — Seoul, Seoul, South Korea (Recruiting)
• Konkuk University Medical Center — Seoul, Seoul, South Korea (Recruiting)
• Asan Medical Center — Seoul, Seoul, South Korea (Recruiting)

Study contacts

• Study coordinator: Yeonsil Moon, Professor

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