Clinical trial NCT05016427: A Study of Possibility of Using Regulatory T Cells(VT301) for Treatment of Alzheimer's Disease
Official title: A Phase 1 Open-Label Dose-Escalating Study to Determine the Safety, and Tolerability of VT301 in Subjects With Mild-to-Moderate Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Alzheimer Disease
Lead sponsor: VTBIO Co. LTD
Sponsor class: INDUSTRY
First posted: 2021-08-23
Enrollment: 12
Sex: ALL
Minimum age (years): 50
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The overall study methods are as follows.

\[Clinical Trials Schedules\] The study consists of a screening period(Visit 1) of up to 30 to 50 days, blood collection visits(Visit 2) for IP generation and administration visits for IP administration(Visit 3), with a follow-up(FU) period of 90 days(Visit 4\~7). During the Follow-up(FU) Period, subjects will visit 4 times for safety, tolerability and efficacy evaluation, with 90 Day being the End of Study(EOS) Visit.

\[Subject screening and blood collection for IP generation\] During Screening Period, subjects will be informed about the study and asked if they want to participate. The subjects and representatives and the caregiver/study partner will be asked to sign consent forms before any study-specific procedures are performed. Screening procedures will be performed to assess whether the subject is eligible to participate in the study. A minimum of approximately 200 mL of the subject's blood will be collected ≥30 days before Baseline and shipped to the IP Manufacturing Agency for generation of the IP. Subjects are required to refrain from consuming alcohol ≥3 days before any blood samples for IP generation are collected. If required (e.g. due to contamination), additional blood samples for IP generation may be collected during an unscheduled visit.


Eligibility criteria: Inclusion Criteria:

1. Male or female 79≥ aged ≥50 years at the time of signing Informed Consent Form.
2. Patients (or their legally acceptable representative) can understand and provide informed consent to participate in the study.
3. Diagnosis of mild-to-moderate AD according to National Institute of Aging and Alzheimer Association (NIA-AA) diagnostic guidelines.
4. Mild-to-moderate AD with MMSE ≥ 10 points and CDR Global Score (CDR-GS) of 0.5 to 2.0 points at Screening.
5. Have ≥1 identified adult caregiver (study partner) who is able to read, understand, and speak the designated language at the study site; either lives with the subject or sees the subject for ≥8 hours/week; and agrees to accompany the subject to each study visit and participate in clinical assessments.

Exclusion Criteria:

1. A medical history of any of the following:

   1. Stroke, transient ischemic attack (TIA), or unexpected loss of consciousness within one year at Screening.
   2. Clinically significant cerebral hemorrhage, bleeding lesion, or cerebrovascular abnormality.
   3. Malignant tumor within 5 years at Screening (no time limit for stable non-metastatic prostate cancer or completely resected non-melanoma skin cancer of 6 months or longer).
   4. Unable to perform MRI tests by enthesis/transplantation of metallic substances (metallic bone fixings, heart devices, etc.) in the body.
   5. Allergic or hypersensitive to the treatment of regulatory T cell components.
2. Patients who have any of the following accompanying diseases/symptoms:

   1. Medical conditions or neurological/neural degenerative disease (excluding AD) considered to cause cognitive impairment or to affect the evaluation of clinical trials (discontinuation, nonconformity, interference, etc.) in the judgment of the investigator.
   2. History of clinically significant gastrointestinal, endocrine, inflammatory or cardiovascular disease that is not controlled by drug/non-drug treatment.
   3. History of mental illness (e.g., schizophrenia, major depression disorder, bipolar disorder, delirium, etc.) that is considered to affect participation in clinical trials under the judgment of the investigator.
   4. History of alcohol or drug abuse or dependence (except caffeine or nicotine).
   5. Vision, hearing, or mobility (behavior) has deteriorated to a degree that interferes with or is unable to perform clinical trial procedures.
   6. Hypersensitive to bee venom.
   7. High blood pressure who are not controlled by drug/non-drug treatment (SBP \> 165 mmHg or DBP \> 96 mmHg).
   8. Hypersensitive to gentamycin.
3. Patients who have any of the following abnormal lab values at Screening:

   1. Urine Drug Screening Test: positive.
   2. Hepatitis B virus surface Antigen (HBsAg): positive.
   3. Anti-Hepatitis C Virus (Anti-HCV): positive.
   4. Anti- Human Immunodeficiency Virus (Anti-HIV): positive.
   5. Sensitization test for bee venom: positive.
   6. Serious renal dysfunction: Serum Creatinine ≥ 1.7 mg/dL.
   7. Clinically significant hepatic dysfunction (one or more of the following):.

      * Serum Alanine Transaminase (ALT) ≥ 2 x upper limit of normal (ULN)
      * Serum Aspartate Transaminase (AST) ≥ 2 x ULN
      * Serum Bilirubin ≥ organ ULN x 2
4. The person with the following drug or need to be administered during the clinical trial period:

   1. Acetylcholine Esterase(AChE) inhibitor, N-methyl-D-aspartate(NMDA) receptor antagonist, or a co-administration of these two drugs (Except if the dose was started more than 90 days before the date of the acquisition of the consent form and can be maintained reliably during administration and clinical trials without changing the dose for more than 60 days).

      * However, the drug corresponding to (a) shall not be duplicated in (b).
   2. Drugs affecting the central nervous system (However, the dose was administered stably 30 days prior to the date of the acquisition of the consent form, except if it can be maintained during the clinical trial period).
   3. Drugs that are not properly administered during the clinical trial period as determined by the other investigator's.
5. The person with the following one or more applicable:

   1. A female subject who is pregnant or breast-feeding.
   2. Fertile female@ subjects who have plans for pregnancy or do not use effective contraception method# during clinical trials period.
   3. A male subject who does not undergo surgical sterilization procedures or surgery without effective contraception method# (with a Fertile female@ partner).

      * A fertile women is a women whose menopause has not occurred since the first menstrual and who has not undergone surgical sterilization procedures or surgery. Non-fertile women are defined as having one or more of the following:

        * 12 months of natural menopause.

          * For natural menopause for 6 months, the concentration of hCG(human Chorionic Gonadotropin) in the blood is 0 to 5 mIU/mL.

            * In case of surgical sterilization procedures or surgery (bilateral ovariectomy, bilateral tubal ligation, etc.)

              * Effective contraception methods recognized in this clinical trial are as follows:
        * Combining either hormonal contraceptives(subdermal implant agents, injections, oral contraceptive, etc.) or spermicide with physical barrier method(condom, contraceptive vaginal diaphragm, vaginal sponge, cervical cap).

          * Transplantation of intrauterine device(IUD) or intrauterine system(copper-loop, hormone-containing intrauterine system).

            * Both male(condom) and female(contraceptive vaginal diaphragm, vaginal sponge, or cervical cap) use physical barrier method.

              * surgical sterilization procedures or surgery (bilateral ovariectomy, bilateral tubal ligation, etc.)
6. A person who has blood donation within 30 days of the date of the acquisition of the consent form.
7. A person who has participated in another clinical trial within 60 days from the time of the acquisition of the consent form and has been given a investigational product(IP) or applied a clinical trial medical instrument.
8. Other persons who are not qualified to participate in clinical trials under the judgment of the investigator's.

Primary outcomes:
measure: All Adverse Events(AE) that occurred from the time of acquisition of consent of the subjects to the time of EOS(End of Study) shall be collected.
timeFrame: Change from Baseline AE at 3 months
measure: Number of subjects with abnormal clinical Physical examination
timeFrame: Change from Baseline Physical examination at 3 months
measure: Number of subjects With Clinically Significant Abnormalities in 12-lead Electrocardiogram
timeFrame: Change from Baseline 12-lead Electrocardiogram at 3 months
measure: Number of subjects with abnormal clinical Laboratory Tests
timeFrame: Change from Baseline clinical Laboratory Tests at 3 months
measure: Number of subjects with abnormal vital signs
timeFrame: Change from Baseline vital signs at 3 months
measure: Change from Screening "Questionnaire: Columbia Suicide Severity Rating Scale(C-SSRS)" at 90 days
timeFrame: Change from Baseline C-SSRS at 3 months
Secondary outcomes:
measure: Change from Baseline "Questionnaire: Alzheimer's Disease Assessment Scale-Cognitive Subscale-13 task(ADAS-Cog-13)" at 90 days
timeFrame: Change from Baseline ADAS-Cog-13 at 3 months
measure: Change from Baseline "Questionnaire: Alzheimer's Disease Cooperative Study-Activities of Daily Living(ADCS-ADL)" at 90 days
timeFrame: Change from Baseline ADCS-ADL at 3 months
measure: Change from Screening "Questionnaire: Mini-Mental State Examination(MMSE)" at 90 days.
timeFrame: Change from Baseline MMSE at 3 months
measure: Change from Screening "Questionnaire: Clinical Dementia Rating(CDR)" at 90 days.
timeFrame: Change from Baseline CDR at 3 months
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Vtbio Co., Ltd
Study officials:
References: