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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03865017




Registration number
NCT03865017
Ethics application status
Date submitted
15/02/2019
Date registered
6/03/2019
Date last updated
5/08/2019

Titles & IDs
Public title
A Safety and Tolerability Study of GB301
Scientific title
A Safety and Tolerability Study of GB301 Given as a Single Intravenous Dose in Subjects With Mild to Moderate Alzheimer's Disease
Secondary ID [1] 0 0
GB301-A01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Regulatory T cells
Other interventions - Saline

Experimental: Regulatory T cells - Biologicals: Autologous Regulatory T cells (1.7*10^5 cells/kg, i.v) other name: GB301

Placebo Comparator: Placebo - Saline+cell suspension solution infusion


Other interventions: Regulatory T cells
The trial will be carried out in Alzheimer's disease patients. The investigators will isolate CD4+CD25+ Tregs from these patients, expand and injection.

Other interventions: Saline
Saline+cell suspension solution infusion

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of subjects With Clinically Significant Abnormalities in 12-lead Electrocardiogram - The number of subjects with normal and abnormal ECG findings will be summarized for each treatment group at each time point. Clinical significance was determined by the investigator.
ECG measures PR interval (ms), QRS interval, QT interval(ms), QTc interval (ms), and heart rate(bpm) for each treatment group at each time point.
Timepoint [1] 0 0
Between Baseline and 12 weeks
Primary outcome [2] 0 0
Number of subjects with abnormal clinical chemistry parameters - Blood samples will be collected for the assessment of following clinical chemistry parameters: Albumin, Total bilirubin, Total protein, Calcium, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), Creatinine, Glucose, Sodium, Potassium, Chloride, Bicarbonate, LDH, FSH, Uricacid
Timepoint [2] 0 0
Between Baseline and 12 weeks
Primary outcome [3] 0 0
Number of subjects with abnormal Hematology parameters - Blood samples will be collected for the assessment of following hematology parameters: red blood cell (RBC) count, Hemoglobin, Hematocrit, mean corpuscular volume (MCV),mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), Platelet, white blood cell (WBC) count, Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil
Timepoint [3] 0 0
Between Baseline and 12 weeks
Primary outcome [4] 0 0
Number of subjects with abnormal Coagulation parameters - Blood samples will be collected for the assessment of following coagulation parameters: Prothrombin Time(PT), International normalized ratio(INR), partial thromboplastin time (PTT)
Timepoint [4] 0 0
Between Baseline and 12 weeks
Primary outcome [5] 0 0
Number of subjects with abnormal Urinalysis parameters - Samples will be collected to measure specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones.
Timepoint [5] 0 0
Between Baseline and 12 weeks
Primary outcome [6] 0 0
Number of subjects with abnormal vital signs - Vital signs, including height (only assessed at Screening), weight, systolic and diastolic blood pressure, heart rate, and body temperature, will be measured after the subject has been in a sitting position for 5 minutes.
Timepoint [6] 0 0
Between Baseline and 12 weeks
Primary outcome [7] 0 0
Number of subjects with abnormal vital signs - Vital signs, including height (?, only assessed at Screening), weight(kg), systolic and diastolic blood pressure(mm Hg), heart rate(bpm), and body temperature(?), will be measured after the subject has been in a sitting position for 5 minutes.
Timepoint [7] 0 0
Between Baseline and 12 weeks
Primary outcome [8] 0 0
Number of subjects with adverse events (AEs) - An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
Timepoint [8] 0 0
Between Baseline and 12 weeks
Primary outcome [9] 0 0
Number of subjects with abnormal physical examination - A full physical examination will include assessments of the general apperance, skin, head, neck, eyes, ears, nose, throat, respiratory, cardiovascular, abdomen, extremities, musculoskeletal, neurological, lymph nodes etc.
Timepoint [9] 0 0
Between Baseline and 12 weeks
Primary outcome [10] 0 0
Columbia Suicide Severity Rating Scale (C-SSRS) - The C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. Some questions are yes/no and some are on a scale of 1 (low severity) to 5 (high severity). Completed suicide and non-fatal suicide events are yes/no questions and results presented are the number of participants with these events.
Timepoint [10] 0 0
Between Baseline and 12 weeks
Secondary outcome [1] 0 0
Change from Baseline in Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog-13) Score - 13-item ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place, and spontaneous speech. Most items are evaluated by tests, but some are dependent on clinician ratings on a 5-point scale. The ADAS-Cog-13 is the ADAS-Cog-11 with 2 additional items: delayed word recall and total digit cancellation. Scores for the ADAS-Cog-13 range from 0 to 85 with higher scores indicating greater dysfunction.
Timepoint [1] 0 0
baseline, 29, 57, and 85 days
Secondary outcome [2] 0 0
Change from baseline in MMSE score - The MMSE is a brief, screening instrument often used in clinical studies to assess dementia severity. The MMSE assesses several aspects of memory and cognitive functioning including orientation, attention, concentration, comprehension, recall, and praxis. The total possible score is 30, with high scores indicating less impairment.
Timepoint [2] 0 0
baseline, 29, 57, and 85 days

Eligibility
Key inclusion criteria
Inclusion criteria:

1. Subjects who have voluntarily agreed to participate in the study and have signed a
human research ethics committee-approved consent form after being briefed on the
clinical study before undergoing any study-related procedure.

2. Male or female subjects aged =40 to =72 years with mild to moderate AD with an MMSE
score at Screening and Baseline of =11.

3. Diagnostic confirmation by positron-emission tomography (PET) with florbetaben or
another approved amyloid PET ligand. A previous amyloid imaging study with a positive
result will be accepted. If none is available, then amyloid PET will be conducted
during the Screening Period.

4. Subjects who have been clinically diagnosed with mild-to-moderate AD according to the
2011 version of the National Institute on Aging and Alzheimer's Association criteria
and =6 month decline in cognitive function.

5. Subjects must have a caregiver/study partner who, in the opinion of the site principal
investigator, has contact with the study subject for a sufficient amount of time (i.e.
at least 6 hours per week) to provide informative responses on protocol assessments,
and is willing and able to participate in all clinic visits. The legally acceptable
representative (if appointed) and caregiver/study partner must provide written
informed consent to participate in the study.

6. Formal education of =8 years.

7. Modified Hachinski Ischaemic Score =4 at Screening Visit.

8. The subject has had a documented computerized tomography or magnetic resonance imaging
scan, interpreted by a radiologist or neurologist, within 36 months prior to
randomization and after the subject met the National Institute of Neurological and
Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders
Association diagnostic criteria for probable AD. The scan must not show evidence for
an alternative etiology for dementia.

9. No active depression and a Geriatric Depression Scale (15 items) score of =5.

10. Subjects should be generally healthy with mobility (ambulatory or ambulatory aided,
i.e. walker or cane), vision and hearing (hearing aid permissible) sufficient for
compliance with testing procedures.

11. Subject, if female, is postmenopausal (last natural menses =24 months) or has
undergone a documented bilateral tubal ligation or hysterectomy. If last natural
menses is <24 months, a serum follicle-stimulating hormone (FSH) value confirming post
menopausal status should be employed, except if documentation of bilateral tubal
ligation or hysterectomy is available.

Women of childbearing potential need to apply at least 1 highly efficient
contraceptive method.

Male subject either agrees to use a highly efficient method of contraception if his
female partner is of childbearing potential or must have been surgically sterilized
prior to the Screening Visit.

Highly efficient methods of contraception are defined as:

- Hormonal methods such as oral, implantable, injectable, or transdermal
contraceptives for a minimum of 1 full cycle before IP administration.

- Total abstinence from sexual intercourse between the Screening Visit and 4 weeks
after the last IP administration.

- Intrauterine device.

- Double barrier method (condoms, sponge, diaphragm, with spermicidal jellies, or
cream).

12. Subjects with the capability of performing all cognitive and other tests required for
this study in the opinion of the investigator.
Minimum age
40 Years
Maximum age
72 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

1. Subjects who have taken drugs known to have or carry the potential for significant
interactions with the IP within 14 days prior to the administration of this IP and
during the study (e.g. non-specific immunosuppressive drugs, specific T cell
immunosuppressive drugs, immunostimulants, immunomodulating agents) or any drugs that
are considered unsuitable by investigator's judgment.

2. Subjects who have donated blood within 30 days prior to Screening or who have
participated in clinical studies of other investigational medicinal products or
commercially available drugs within 60 days prior to Screening.

3. Subjects who have experienced significant AEs or hypersensitivity to previous Treg
therapy.

4. Subjects whom the investigator finds unsuitable for the clinical study participation
based on clinically significant laboratory results, vital signs, ECG, or other
examinations.

5. Subjects with a history of mental illness that may interfere with their participation
in the clinical study, such as schizophrenia or bipolar affective disorder according
to the investigator's judgment.

6. Subjects with any medical or neurological/neurodegenerative condition (other than AD)
that, in the opinion of the investigator, might be a contributing cause to the
subject's cognitive impairment or could lead to discontinuation, lack of compliance,
interference with study assessments, or safety concerns.

7. Subjects who have had a stroke or transient ischemic attack or unexplained loss of
consciousness in the past 1 year.

8. Subjects who have a history of clinically relevant brain hemorrhage, bleeding
disorder, or cerebrovascular abnormalities.

9. Subjects with clinically relevant gastrointestinal, endocrine, inflammatory, or
cardiovascular diseases that are not controlled by diet or medication.

10. Subjects with a history of alcohol or other substance abuse or dependence (with the
exception of caffeine and nicotine) or a positive drug screen at Screening
(amphetamines, barbiturates, cocaine, methamphetamine, methadone, opiates,
phencyclidine, and tetrahydrocannabinol).

11. Subject has serum hepatitis, is a carrier of the hepatitis B virus surface antigen, is
a carrier of the hepatitis C antibody, or is seropositive for human immunodeficiency
virus antibodies as confirmed at Screening.

12. Subject has a history of cancer within 3 years of Screening with the exception of
fully excised non-melanoma skin cancers or non-metastatic prostate cancer that has
been stable for =6 months.

13. Subjects with uncontrolled hypertension with a resting systolic blood pressure
exceeding 165 mmHg or diastolic blood pressure exceeding 96 mmHg.

14. Subjects with severe renal impairment (serum creatinine =1.7 mg/dL) at Screening.

15. Subjects with clinically relevant hepatic impairment (any of levels of alanine
transaminase, aspartate transaminase, or bilirubin =2.0 times the upper limit of
normal) at Screening.

16. Subjects who are taking or are expected to take a prohibited concomitant medication,
such as steroid drugs and supplements that improve the blood circulation (e.g. omega-3
fatty acids) during the study. Concomitant medication affecting the central nervous
system should be stable for =1 month before Screening and should not change during the
study. Standard AD medication is permitted if initiated =3 months before enrollment
and on a stable dose for =2 months.

17. Subjects who are unsuitable for participating in this clinical study for any other
reason, based on the investigator's judgment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Bht Lifescience Australia Pty Ltd - Brisbane
Recruitment postcode(s) [1] 0 0
4000 - Brisbane

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GMP BIO Co., LTD.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
BHT Lifescience Austrailia Pty Ltd.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study is to evaluate the safety and tolerability of multiple
intravenous (IV) infusions at a single dose strength of GB301 in subjects with mild to
moderate AD.
Trial website
https://clinicaltrials.gov/show/NCT03865017
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jaeyoon Kim
Address 0 0
Director
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Jaeyoon Kim
Address 0 0
Country 0 0
Phone 0 0
+82-2-553-9777
Fax 0 0
Email 0 0
jykim@gmp.co.kr
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03865017