A Study to Evaluate Efficacy and Safety of BAC in Patient With Alzheimer's Disease or Vascular Dementia

Study Overview
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Brief Summary
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A Randomized, Double-Blind, Vehicle-Controlled, Parallel, Phase II Study to Evaluate Efficacy and Safety of BAC in Patient with Alzheimer's Disease or Vascular Dementia

Detailed Description
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This study was designed as a randomized, double-blind, vehicle-controlled and parallel trial to evaluate the efficacy and safety of BAC in patients with Alzheimer's disease or vascular dementia. The investigation product, BAC, is a potential anti-inflammatory agent consisted of Multi-Glycan Complex (MGC) from the Soybean extract. It aims to reduce the neruoinflammation in the Alzhemimer's disease and vascular dementia. In each study site, eligible patients were randomized and stratified to 1 of 2 dementia types (Alzheimer's disease and non-Alzheimer's disease) in 3:1 ratio to receive either one of topical application of BAC or BAC matched vehicle, topical application on external nasal skin, scalp, and neck, 2 times daily, 30 g/day. The treatment duration for each patient was 12 weeks, which consisted of 6 visits located at Screening (within 2 weeks before Baseline visit), Baseline (Week 0), Weeks 2, 4, 8, and Week 12 (Final). During the treatment period, patients may continue to receive medications or treatments routinely used for Alzheimer's disease or vascular dementia except those prohibited under this protocol.

Official Title
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A Randomized, Double-Blind, Vehicle-Controlled, Parallel, Phase II Study to Evaluate Efficacy and Safety of BAC in Patient With Alzheimer's Disease or Vascular Dementia

Conditions
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Alzheimer's Disease or Vascular Dementia

Intervention / Treatment
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* Drug: BAC treatment
* Drug: Matched vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: With either gender aged at least 40 years old With a diagnosis of one of the following disease i. Vascular dementia according to the NINDS-AIREN International Workshop criteria or ii. Alzheimer's disease according to the NIAAA criteria iii. Mixed dementia (possible Alzheimer's disease with cerebrovascular disease) according to the NIAAA criteria Note: NINDS-AIREN: National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherche et l'Enseignement en Neurosciences NIAAA: National Institute on Aging-Alzheimer's Association With mild-to-moderate dementia (score of the Mini-Mental State Examination (MMSE) defined as between 10 to 24 and score of ADAS-Cog as at least 12) Able to read, write, communicate, and understand cognitive testing instructions Having a responsible caregiver who spends at least 4 hours daily with the patient. The caregiver will accompany the patient to all study visits, , supervise administration of study drug, and be able to assess the patient's condition Patients and the responsible caregiver willing and able to provide written informed consent form Exclusion Criteria: With large vessel thrombosis (thrombotic stroke occurring in large arteries) With radiological evidence of other brain disorders (subdural hematoma, post-traumatic / post-surgery) With dementia caused by other brain diseases except Alzheimer's disease and vascular dementia (e.g. Parkinson's disease, demyelinated disease of the central nervous system, tumor, hydrocephalus, head injury, central nervous system infection including syphilis, acquired immune deficiency syndrome, etc.) With clinical evidence of pulmonary, hepatic, gastrointestinal, metabolic, endocrine or other life threatening diseases judged by investigators not suitable to enter the study With clinically unstable hypertension, diabetes mellitus, and cardiac disease for the last 3 months Ever hospitalized for stroke or with acute coronary syndrome in the previous 3 months prior to screening Drug or alcohol abuse within the previous 12 months of screening. With one of the following abnormal laboratory parameters: hemoglobin < 10 mg/dL or platelet < 100*109/L; creatinine or total bilirubin more than 1.5 times the upper limit value; alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphates (ALP), γ-glutamyl transferase (γ-GT) more than 2 times the upper limit of normal, or thyroid-stimulating hormone (TSH) more than 2.5 times the upper limit value or less than the lower limit value of normal With severe depression graded by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and Cornell Scale for Depression in Dementia (CSDD) With any uncontrolled illness (including, but not limited to, any of the following: ongoing or active infection including hepatitis B, C, and HIV, active bleeding, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris or, cardiac arrhythmia) judged by the investigator that entering the trial may be detrimental to the patient With known or suspected hypersensitivity to any ingredients of study product and vehicle Pregnant or lactating or premenopausal with childbearing potential but not taking reliable contraceptive method(s) during the study period Note: Reliable contraceptive methods will consider as below: Established use of oral, injected or implanted hormonal methods of contraception > 3 months prior to baseline. Placement of an intrauterine device (IUD) or intrauterine system (IUS) > 3 months prior to baseline. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository Partner male sterilization (i.e., vasectomy) > 1 month of screening Enrollment in any investigational drug trial within 4 weeks of screening visit Experienced dosage increment of routinely use in drugs listed as follows within past three months before Screening visit medications/treatments for Alzheimer's disease or vascular dementia antipsychotic medications including but not limited to selective serotonin reuptake inhibitors (SSRIs), benzodiazepine (BZD) Vitamin B12 drugs for thyroid disease Current antiplatelet drug (antiaggregant) except dosage including but not limited to aspirin <= 100mg/day, clopidogrel <= 75mg/day, ticagrelor <= 180mg/day, dipyridamole <= 400mg/day Caregivers who have psychotic symptoms, are imminently suicidal, have an unstable medical condition (e.g. recent heart attack, recent stroke, episodes of dizziness, fainting attacks) or significant orthopaedic problems.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BAC treatment<br>BAC, topical application on external nasal skin, scalp, and neck, 2 times daily, 30 g/day for 12 weeks | Drug: BAC treatment<br>* BAC, topical application on external nasal skin, scalp, and neck, 2 times daily, 30 g/day for 12 weeks<br>* Other names: CSTC1-BAC;|
| Placebo Comparator: Matched vehicle<br>Matched vehicle, topical application on external nasal skin, scalp, and neck, 2 times daily, 30 g/day for 12 weeks | Drug: Matched vehicle<br>* BAC matched vehicle, topical application on external nasal skin, scalp, and neck, 2 times daily, 30 g/day for 12 weeks<br>* Other names: Placebo control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Alzheimer Disease Assessment Scale-cognitive (ADAS-cog) Score at Week 12 Visit Compared to Baseline | The Alzheimer's Disease Assessment Scale- Cognitive (ADAS-Cog) Subscale test is the standard assessment tool and one of the most popular cognitive testing instrument in clinical trials. It is designed to assess various cognitive abilities such as those associated with memory, language and praxis. It consists of 11 parts: 1. Word Recall Task; 2. Naming Task; 3: Commands; 4: Constructional Praxis; 5. Ideational Praxis; 6. Orientation; 7. Word Recognition Task; 8. Language; 9. Comprehension of Spoken Language; 10. Word Finding Difficulty; and 11. Remembering Test Instructions. Scores range from 0 to 70 with lower scores indicating lesser severity. ADAS-Cog was measured at Screening, Randomization/Baseline, Week 4, Week 8 and Week 12. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ADAS-cog Score at All Post Treatment Visits (Except Week 12 Visit) Compared to Baseline | The Alzheimer's Disease Assessment Scale- Cognitive (ADAS-Cog) Subscale test is the standard assessment tool and one of the most popular cognitive testing instrument in clinical trials. It is designed to assess various cognitive abilities such as those associated with memory, language and praxis. It consists of 11 parts: 1. Word Recall Task; 2. Naming Task; 3: Commands; 4: Constructional Praxis; 5. Ideational Praxis; 6. Orientation; 7. Word Recognition Task; 8. Language; 9. Comprehension of Spoken Language; 10. Word Finding Difficulty; and 11. Remembering Test Instructions. Scores range from 0 to 70 with lower scores indicating lesser severity. ADAS-Cog was measured at Screening, Randomization/Baseline, Week 4, Week 8 and Week 12. | Week 4, 8 | 
| Clinician's Interview Based Impression of Change-Plus Caregiver Input (CIBIC-plus) Score at All Post Treatment Visits | This is a global measure of detectable change in cognition, function and behavior. The format for CIBIS/CIBIC-Plus consists of the assessment of an independent clinician based on observation of the patient at an interview, and information provided by the caregiver. The clinician's assessing severity at baseline and overall impression for assessing severity of the global change in disease severity, compared with baseline, is rated. The CIBIS/CIBIC plus examined general, cognitive, and behavioral function and activities of daily living on a 7-point categorical rating scale, ranging from a score of 0 indicating Not assessed, to a score of 7 indicating Among the most extremely ill patients for CIBIS and ranging from 1 indicating Very much improved, to a score of 7 indicating Marked worsening, and with a score of 4 indicating no change for CIBIC-Plus. CIBIS was measured at Randomization visit and CIBIC-Plus was measured at Week 4, Week 8, and Week 12. | Week 4, 8, 12 | 
| Change in Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Score at All Post Treatment Visits Compared to Baseline | An inventory of informant based items to assess activities of daily living and instrumental activities of daily living, i.e. functional performance, of Alzheimer's disease (AD). It consists of 23-item inventory of ADL, rated based on extent of assistance the patient requires (independently, with supervision, with physical help): 0 (total independence in performing an activity) to 4 (total inability to act independently). Each question varies in the number of options to choose. Total score range: 0 to 78; higher scores indicate less functional impairment. ADL will be measured at Randomization/Baseline, Week 4, Week 8, and Week 12. | Week 4, 8, 12 | 
| Change in Mini-Mental State Examination (MMSE) Score at All Post Treatment Visits Compared to Baseline | This is a multi-item instrument that examines orientation, registration, attention, calculation, recall, visuospatial abilities and language. The score ranges from 0 to 30, with higher scores indicating better cognitive function. MMSE was measured at Screening, Randomization/Baseline, Week 4, Week 8, and Week 12. | Week 4, 8, 12 | 
| Change in Neuropsychiatric Inventory (NPI) Score at All Post Treatment Visits Compared to Baseline: NPI-10 Frequency × Severity | The NPI is the behavior instrument most widely used in clinical trials of anti-dementia agents. The NPI uses a screening strategy to minimize administration time, examining and scoring only those behavioral domains with positive responses to screening questions. Both the frequency and the severity of each behavior are determined. Information for the NPI is obtained from a caregiver familiar with the patient's behavior. The NPI assesses 10 behavioral domains (10-item NPI, section A J) common in dementia. Each NPI domain is scored by the caregiver based on a standardized interview administered by the clinician. Frequency is scored from 1 (occasionally) to 4 (very frequently) and severity is rated from 1 (mild) to 3 (severe). The score for each domain is frequency multiplied by severity. Therefore, the score ranges from 1 to 12 with higher scores indicate worse condition. NPI was measured at Randomization/Baseline, Week 4, Week 8, and Week 12. | Week 4, 8, 12 | 
| Change in Neuropsychiatric Inventory (NPI) Score at All Post Treatment Visits Compared to Baseline: NPI-10 Caregiver Distress Score | The NPI is the behavior instrument most widely used in clinical trials of anti-dementia agents. The NPI uses a screening strategy to minimize administration time, examining and scoring only those behavioral domains with positive responses to screening questions. Both the frequency and the severity of each behavior are determined. Information for the NPI is obtained from a caregiver familiar with the patient's behavior. The NPI assesses 10 behavioral domains (10-item NPI) common in dementia. Each NPI domain is scored by the caregiver based on a standardized interview administered by the clinician. NPI-10 Caregiver Distress score is scored for associated caregiver distress from 0 (no distress) to 5 (very severe or extreme). Higher scores indicate greater distress. NPI was measured at Randomization/Baseline, Week 4, Week 8, and Week 12. | Week 4, 8, 12 | 
| Change in Neuropsychiatric Inventory (NPI) Score at All Post Treatment Visits Compared to Baseline: NPI-12 Frequency × Severity Score | The NPI is the behavior instrument most widely used in clinical trials of anti-dementia agents. The NPI uses a screening strategy to minimize administration time, examining and scoring only those behavioral domains with positive responses to screening questions. Both the frequency and the severity of each behavior are determined. Information for the NPI is obtained from a caregiver familiar with the patient's behavior. The NPI assesses 12 behavioral domains (12-item NPI) common in dementia. Each NPI domain is scored by the caregiver based on a standardized interview administered by the clinician. Frequency is scored from 1 (occasionally) to 4 (very frequently) and severity is rated from 1 (mild) to 3 (severe). The score for each domain is frequency multiplied by severity. Therefore, the score ranges from 1 to 12 with higher scores indicate worse condition. NPI was measured at Randomization/Baseline, Week 4, Week 8, and Week 12. | Week 4, 8, 12 | 
| Change in Neuropsychiatric Inventory (NPI) Score at All Post Treatment Visits Compared to Baseline: NPI-12 Caregiver Distress Score | The NPI is the behavior instrument most widely used in clinical trials of anti-dementia agents. The NPI uses a screening strategy to minimize administration time, examining and scoring only those behavioral domains with positive responses to screening questions. Both the frequency and the severity of each behavior are determined. Information for the NPI is obtained from a caregiver familiar with the patient's behavior. The NPI assesses 12 behavioral domains (12-item NPI) common in dementia. Each NPI domain is scored by the caregiver based on a standardized interview administered by the clinician. NPI-12 Caregiver Distress score is scored for associated caregiver distress from 0 (no distress) to 5 (very severe or extreme). Higher scores indicate greater distress. NPI was measured at Randomization/Baseline, Week 4, Week 8, and Week 12. | Week 4, 8, 12 | 
| Number of Participants With Adverse Events | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a study medication and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a study medication, whether or not related to the study medication. Laboratory abnormalities should not be recorded as AEs unless determined to be clinically significant by the Investigator. The number of participants with adverse events within the BAC and placebo groups was determined. | AEs were reported through the study completion (up to 12 weeks) |