Clinical trial NCT02886494
Conditions: Alzheimer's Disease or Vascular Dementia
Sponsor: Charsire Biotechnology Corp.
Start date: 2016-12-01; Completion date: 2018-11-01
Enrollment: 80 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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:
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.

Arms: arm 1: BAC, topical application on external nasal skin, scalp, and neck, 2 times daily, 30 g/day for 12 weeks arm 2: Matched vehicle, topical application on external nasal skin, scalp, and neck, 2 times daily, 30 g/day for 12 weeks
Interventions: intervention 1: BAC treatment intervention 2: Matched vehicle
Intervention descriptions: intervention 1: BAC, topical application on external nasal skin, scalp, and neck, 2 times daily, 30 g/day for 12 weeks intervention 2: BAC matched vehicle, topical application on external nasal skin, scalp, and neck, 2 times daily, 30 g/day for 12 weeks

Protocol documents:
Prot_SAP_000.pdf: 
BAC for Alzheimer’s Disease or Vascular Dementia 
(Project Number: BAC-02) 
Version: 2.0 
Date: 24APR2017 
 
Sponsor: Charsire Biotechnology Corp. 
Page 1 of 9
 
 
 
 
 
 
 
 
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 
 
 
 
 
NCT Number 
NCT02886494 
Document Version 
V2.0 
Document Date 
24APR2017 
Sponsor 
Charsire Biotechnology Corp. 
 
 
 


BAC for Alzheimer’s Disease or Vascular Dementia 
(Project Number: BAC-02) 
Version: 2.0 
Date: 24APR2017 
 
Sponsor: Charsire Biotechnology Corp. 
Page 2 of 9
PROTOCOL SUMMARY 
Full Title 
 
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 
Short Title 
BAC for Alzheimer’s Disease or Vascular Dementia Phase II Study 
Project No 
BAC-02 
Study Phase 
Phase II 
Sponsor 
Charsire Biotechnology Corp. 
Objectives 
 
To evaluate the efficacy and safety of BAC in patients with 
Alzheimer’s disease or vascular dementia 
Study Design 
Randomized, double-blind, vehicle-controlled, parallel study 
Study Population 
Patient aged at least 40 years old in United States diagnosed with 
Alzheimer’s disease or vascular dementia 
Number of Patients  
The sample size is determined to be 45 versus 15 patients (3:1 ratio) 
for Treatment versus Control groups, 60 patients in total. To ensure 
the completion of 60 evaluable (per-protocol population) patients, 
around 75 patients will be recruited. 
Study Product, Dose, 
Route, Regimen 
BAC (vapor fraction from seeds of Glycine max (L.) Merr. and 
composition thereof), topical application on external nasal skin, 
scalp, and neck, 2 times daily, 30g/day 
During the treatment period, patients may continue to receive 
routinely used medications or treatments for Alzheimer’s disease or 
vascular dementia. 
Duration of 
Administration 
Twelve weeks 
Study Visits 
Screening, Randomization (Baseline) Treatment (Weeks 2, 4, and 8 
compared to Baseline), Final (Week 12) 
Patient Assignment 
In each study site, patients who meet all eligible requirements for 
entry into the study will be randomized and stratified into 1 of 2 
dementia types (Alzheimer’s disease and non- Alzheimer’s disease) 
into treatment group or vehicle control group in 3:1 ratio as shown 
below: 
 


BAC for Alzheimer’s Disease or Vascular Dementia 
(Project Number: BAC-02) 
Version: 2.0 
Date: 24APR2017 
 
Sponsor: Charsire Biotechnology Corp. 
Page 3 of 9
Treatment Group: 
BAC  
Control Group: 
Matched vehicle  
Note: Dementia types (Alzheimer’s disease and non- Alzheimer’s disease) are 
classified as follows: 
1. Alzheimer’s disease: Alzheimer's disease according to the NIAAA criteria + 
"Mixed" dementia (possible Alzheimer's disease with cerebrovascular disease) 
according to the NIAAA criteria 
2. Non- Alzheimer’s disease: Vascular dementia according to the NINDS-AIREN 
International Workshop criteria  
Patients Inclusion 
Criteria 
A patient is eligible for the study if all of the following apply:  
1. With either gender aged at least 40 years old 
2. 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:  
a. NINDS-AIREN: National Institute of Neurological Disorders and Stroke 
and Association Internationale pour la Recherche et l'Enseignement en 
Neurosciences 
b. NIAAA: National Institute on Aging-Alzheimer's Association 
3. 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) 
4. Able to communicate and understand cognitive testing 
instructions 
5. 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 


BAC for Alzheimer’s Disease or Vascular Dementia 
(Project Number: BAC-02) 
Version: 2.0 
Date: 24APR2017 
 
Sponsor: Charsire Biotechnology Corp. 
Page 4 of 9
6. Patients and the responsible caregiver willing and able to 
provide written informed consent form. Patients who lack 
capacity to consent must be in agreement with entering into the 
study and have a personal legally authorized representative 
giving written informed consent to their participation. 
Patients Exclusion 
Criteria 
Any patient meeting any of the exclusion criteria will be excluded 
from study participation. 
1. With large vessel thrombosis (thrombotic stroke occurring in 
large arteries) 
2. With radiological evidence of other brain disorders (subdural 
hematoma, post-traumatic / post-surgery)  
3. 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.) 
4. With clinical evidence of pulmonary, hepatic, gastrointestinal, 
metabolic, endocrine or other life threatening diseases judged by 
investigators not suitable to enter the study 
5. With clinically unstable hypertension, diabetes mellitus, and 
cardiac disease for the last 3 months 
6. Ever hospitalized for stroke or with acute coronary syndrome in 
the previous 3 months prior to screening 
7. Drug or alcohol abuse within the previous 12 months of 
screening. 
8. 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 


BAC for Alzheimer’s Disease or Vascular Dementia 
(Project Number: BAC-02) 
Version: 2.0 
Date: 24APR2017 
 
Sponsor: Charsire Biotechnology Corp. 
Page 5 of 9
9. With severe depression graded by Diagnostic and Statistical 
Manual of Mental Disorders, Fifth Edition (DSM-5) and Cornell 
Scale for Depression in Dementia (CSDD) 
10. 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  
11. With known or suspected hypersensitivity to any ingredients of 
study product and vehicle 
12. 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:  
a. Established use of oral, injected or implanted hormonal methods of 
contraception > 3 months prior to baseline. 
b. Placement of an intrauterine device (IUD) or intrauterine system (IUS) > 3 
months prior to baseline. 
c. Barrier methods of contraception: Condom or Occlusive cap (diaphragm 
or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository 
d. Partner male sterilization (i.e., vasectomy) > 1 month of screening 
13. Enrollment in any investigational drug trial within 4 weeks of 
screening visit 
14. Experienced dosage increment of routinely use in drugs listed as 
follows within past three months before Screening visit 
a. medications/treatments for Alzheimer’s disease or vascular 
dementia 
b. antipsychotic medications including but not limited to 
selective serotonin reuptake inhibitors (SSRIs), 
benzodiazepine (BZD) 
c. Vitamin B12 
d. drugs for thyroid disease 


BAC for Alzheimer’s Disease or Vascular Dementia 
(Project Number: BAC-02) 
Version: 2.0 
Date: 24APR2017 
 
Sponsor: Charsire Biotechnology Corp. 
Page 6 of 9
15. Current antiplatelet drug (antiaggregant) except dosage 
including but not limited to aspirin  100mg/day, clopidogrel  
75mg/day, ticagrelor  180mg/day, dipyridamole  400mg/day 
16. 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.  
Primary Endpoint 
Efficacy:  
Change in Alzheimer Disease Assessment Scale-cognitive (ADAS-
cog) score at Week 12 visit compared to baseline 
Secondary Endpoints Efficacy: 
1. Change in ADAS-cog score at all post treatment visits (except 
Week 12 visit) compared to baseline 
2. Clinician's Interview Based Impression of Change-Plus 
Caregiver Input (CIBIC-plus) score at all post treatment visits 
3. Change in Alzheimer's Disease Cooperative Study Activities of 
Daily Living (ADCS-ADL) score at all post treatment visits 
compared to baseline 
4. Change in MMSE score at all post treatment visits compared to 
baseline 
5. Change in Neuropsychiatric Inventory (NPI) score at all post 
treatment visits compared to baseline 
Safety: 
1. Adverse event incidence 
2. Change in physical examination results 
3. Net change from baseline in laboratory test results  
4. Net change from baseline in vital signs 
Statistical Analysis 
Analysis Population 
Two data sets will be introduced for statistical analysis.  
Intent-to-treat (ITT) population: 
– All randomized patients who have received at least one dose 
study medication.  
Per-protocol (PP) population: 


BAC for Alzheimer’s Disease or Vascular Dementia 
(Project Number: BAC-02) 
Version: 2.0 
Date: 24APR2017 
 
Sponsor: Charsire Biotechnology Corp. 
Page 7 of 9
– A subset of ITT population 
– Fulfill all inclusion and exclusion criteria 
– Accumulatively dosed with at least 63 days of study drug and 
with at least 75% of dosing compliance during treatment period 
– With ADAS-cog score evaluation at or after Week 8 visit 
– Did not receive any prohibited treatment during the study 
Efficacy endpoints will be analyzed on ITT and PP population. 
Demographics, baseline characteristics, and safety endpoints will be 
analyzed on ITT population. The conclusion of efficacy will be 
made according to the results of ITT population analysis. 
 
Analyses 
Demographics and baseline characteristics will be summarized for 
each group by using descriptive statistics. 
The efficacy endpoints will be compared between the BAC group 
and vehicle group. The primary endpoint of this study is change in 
ADAS-cog score at Week 12 visit compared to baseline. The test 
will be performed by ANCOVA with treatment group and center as 
factor and with baseline score as covariate. Test treatment group 
will be declared superiority if the null hypothesis is rejected and 
improvement in ADAS-cog of test product group is greater than that 
of matched vehicle group. 
As for secondary endpoints, change in ADAS-cog score at all post-
treatment visits (except Week 12 visit) compared to baseline will be 
analyzed by ANCOVA with treatment group and center as factor 
and with baseline score as covariate. Same statistical analysis 
methods will be applied for other secondary endpoints such as 
changes in ADCS-ADL score, MMSE score, and NPI score at all 
post treatment visits compared to baseline. The CIBIC-plus score at 
all post treatment visits will be presented by transition table. 
All treatment group comparisons will be conducted with 
significance level of 0.05, using 2-tailed tests. 
For safety analyses, adverse events will be reported by treatment 
groups and by physiological systems as appropriate. Incidence of 
adverse events between treatments will be analyzed by CMH test. 


BAC for Alzheimer’s Disease or Vascular Dementia 
(Project Number: BAC-02) 
Version: 2.0 
Date: 24APR2017 
 
Sponsor: Charsire Biotechnology Corp. 
Page 8 of 9
Changes in physical examinations will be displayed for each 
individual system. Net changes from pre-treatment laboratory test 
results and vital signs will be analyzed by descriptive statistics. 
All treatment group comparisons will be conducted with 
significance level of 0.05, using 2-tailed tests. 
Additionally, descriptive statistics will be provided for all of the 
endpoints. Frequency table will be provided for categorical data, 
while mean, standard deviation, maximum, minimum, median, inter-
quartile range (IQR), and 95% two-sided confidence interval will be 
calculated for continuous measurements.  
 
 
 


BAC for Alzheimer’s Disease or Vascular Dementia 
(Project Number: BAC-02) 
Version: 2.0 
Date: 24APR2017 
 
Sponsor: Charsire Biotechnology Corp. 
Page 9 of 9
 
SCHEDULE OF ASSESSMENTS 
Visit 
Screening 
Randomization1 
(Baseline) 
Treatment 
Final 
Visit No. 
1 
2 
3 
4 
5 
6 
Weeks relative to Baseline visit 
-2~0 
0 
2 
4 
8 
12 
Visit Window (days) 
NA 
NA 
4 
4 
4 
4 
Informed consent signed and given  
X 
 
 
 
 
 
Screening number assignment 
X 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
Demographic data & medical history 
X 
 
 
 
 
 
Inclusion and exclusion criteria 
X 
X 
 
 
 
 
Pregnancy test for applicable patients 
X 
 
 
 
 
 
Imaging (CT/MRI) 
X5 
 
 
 
 
 
ADAS-cog 
X 
X 
 
X 
X 
X 
CIBIS/CIBIC-plus2 
 
X 
 
X 
X 
X 
ADCS-ADL 
 
X 
 
X 
X 
X 
MMSE 
X 
X 
 
X 
X 
X 
NPI 
 
X 
 
X 
X 
X 
Vital signs 
X 
X 
X 
X 
X 
X 
Physical examinations 
X 
X  
X 
X 
X 
X 
Laboratory test 
X3 
X4  
 
 
 
X 
Record concomitant medication(s) 
X 
X  
X 
X 
X 
X 
Record AE 
 
X 
X 
X 
X 
X 
Dispense trial medication 
 
X 
X 
X 
X 
 
Dispense Subject Diary 
 
X 
X 
X 
X 
 
Return trial medication 
 
 
X 
X 
X 
X 
Return Subject Diary 
 
 
X 
X 
X 
X 
Complete exit form 
 
 
 
 
 
X  
Dismiss patient 
 
 
 
 
 
X  
 
1. Can be on the same day of Screening visit if patient meets entry criteria 
2. Randomization visit: CIBIS; Other Visits: CIBIC-plus 
3. Laboratory test results within 7 days before Screening visit are acceptable. 
4. Laboratory test results within 21 days before Randomization visit are acceptable and can be used as baseline 
measurement. If laboratory test results within past 21 days are not available, the laboratory test has to be 
performed. 
5. Results of CT/MRI (computed tomography/ magnetic resonance imaging) obtained within 12 months before 
Screening visit are acceptable