<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04482413</url>
  </required_header>
  <id_info>
    <org_study_id>AST-ADP2-US02</org_study_id>
    <nct_id>NCT04482413</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Safety and Efficacy of AstroStem in Treatment of Alzheimer's Disease</brief_title>
  <official_title>A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of AstroStem, Autologous Adipose Tissue Derived Mesenchymal Stem Cells, in Patients With Alzheimer's Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nature Cell Co. Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nature Cell Co. Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase 2b randomized, double-blind, Placebo-controlled study with 2 treatment arms,&#xD;
      to compare the efficacy and safety of AstroStem vs. Placebo treatment in patients with mild&#xD;
      Alzheimer's Disease(AD). Eligible patients diagnosed with AD within one year of the start of&#xD;
      treatment will be enrolled. Patients who are randomized into the treatment group will be&#xD;
      administered via intravenously AstroStem every 4 weeks from Week 0 to Week 36. On the other&#xD;
      hand, patients who are randomized into the placebo control group will receive Placebo every 4&#xD;
      weeks from Week 0 to Week 36. After the final administration, patients will be scheduled for&#xD;
      two follow-up visits, at Weeks 44 and 52, to assess efficacy and safety endpoints.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">February 1, 2023</start_date>
  <completion_date type="Anticipated">December 20, 2024</completion_date>
  <primary_completion_date type="Anticipated">May 30, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>SUVR (Standard Uptake Value Ratio)</measure>
    <time_frame>Baseline and 52 Weeks</time_frame>
    <description>Standard Uptake Value Ratio (SUVR) of the Amyloid PET scan</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>CDR-SB score (Clinical Dementia Rating Sum of Boxes)</measure>
    <time_frame>Baseline and 52 Weeks</time_frame>
    <description>Changes of CDR-SOB from baseline at Week 52 Score range: 0-18.0 0 = normal, 0.5-4.0 = questionable cognitive dementia, 4.5-9.0 = mild dementia, 9.5-15.5 = moderate dementia, and 16.0-18.0 = severe dementia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ADAS-Cog-11 score (Alzheimer's Disease assessment Scale-Cognitive Subscale (11 items))</measure>
    <time_frame>Baseline and 52 Weeks</time_frame>
    <description>Change of ADAS-Cog (Alzheimer's Disease Assessment Scale-cognitive subscale) from Baseline at Week 52 Score range: 0-70 A score of 70 represents the most severe impairment and 0 represents the least impairment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MMSE (Mini-mental status examination)</measure>
    <time_frame>Baseline and 52 Weeks</time_frame>
    <description>Change from baseline to Week 52 in the Mini-mental status examination (MMSE) score. The Mini-Mental State Exam (MMSE) is a widely used test of cognitive function among the elderly; it includes tests of orientation, attention, memory, language and visual-spatial skills. The Mini-Mental State Examination (MMSE) or Folstein test is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ADCS-ADL-MCI (Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory)</measure>
    <time_frame>Baseline and 52 Weeks</time_frame>
    <description>Change from baseline to Week 52 in the ADCS-ADl MCI 0-53 A score of 0 represents the most severe impairment and 53 represents the least impairment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C-SSRS (Columbia Suicide Severity Rating Scale)</measure>
    <time_frame>Baseline and 52 Weeks</time_frame>
    <description>Change from baseline to Week 52 in the Columbia Suicide Severity Rating Scale (C-SSRS) score. The suicidal ideation severity subscale ranges from 1 to 5 (with higher number indicating more severe ideation). The intensity of ideation subscale includes 5 questions each one ranging from 1 to 5 (with higher number indicating more intense ideation). The suicidal behavior subscale includes 4 yes/no questions. The suicidal behavior lethality subscale inquires about the level of actual or potential medical damage.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NPI (Neuropsychiatric Inventory)</measure>
    <time_frame>Baseline and 52 Weeks</time_frame>
    <description>Change from baseline to Week 52 in the Neuropsychiatric Inventory (NPI) score. The NPI is a structured interview with a caregiver or qualified study partner (defined as having direct contact &gt; 2 days/week) that evaluates both presence and severity of 12 neuropsychiatric features which include: delusions, hallucinations, dysphoria, anxiety, agitation/aggression, euphoria, disinhibition, irritability, lability, apathy, aberrant motor behavior, night-time behavior, and appetite/ eating changes. If the response to the domain question is &quot;No&quot;, the informant goes to the next question. If &quot;Yes&quot;, the informant then rates both the Severity of the symptoms present within the last month on a 3-point scale ranging from 1 to 3 (mild to severe).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment related Adverse Events</measure>
    <time_frame>Baseline and 52 Weeks</time_frame>
    <description>Number of subjects with treatment related adverse events as assessed by analysis of adverse events including symptoms, and abnormal findings on physical examination, vital signs, ECG, and standard laboratory examination results</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Alzheimer Disease</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Treatment group will be administered via intravenously AstroStem which consists of two syringes and each syringe contains 2.0 x 10^8 cells / 20 mL of saline with 30% auto-serum.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo control group will receive AstroStem Placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AstroStem</intervention_name>
    <description>Treatment group receive AstroStem(Autologous adipose tissue derived mesenchymal stem cells, AdMSCs) every 4 weeks from Week 0 to Week 36.</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo control group receive 20 mL of Saline and auto serum every 4 weeks from Week 0 to Week 36.</description>
    <arm_group_label>Placebo Control</arm_group_label>
    <other_name>AstroStem Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female patients aged 50 and above at the time of signing the Informed Consent&#xD;
             Form&#xD;
&#xD;
          -  Patients who can understand and provide written informed consent (assent)&#xD;
&#xD;
          -  Patients who have a diagnosis of probable mild Alzheimer's Disease(AD) according to&#xD;
             the National Institute of Neurological and Communicative Disorders and Stroke;&#xD;
             Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria within&#xD;
             one year of the start of treatment&#xD;
&#xD;
          -  Patients who have an MMSE Score of 20 to 24 at screening&#xD;
&#xD;
          -  Patients who have a Clinical Dementia Rating (CDR)-Global Score of 0.5 to 1 at&#xD;
             baseline&#xD;
&#xD;
          -  Patients who have any FDA-approved AD medication (donepezil, galantamine, memantine,&#xD;
             rivastigmine or any combination) since their AD diagnosis receiving a stable dose of&#xD;
             medical teratment for at least 12 weeks prior to Screening and were to stay on a&#xD;
             stable dose during the study&#xD;
&#xD;
          -  Patients who have one (or more) identified adult caregiver (study partner) who is able&#xD;
             to read, understand, and speak the designated language at the study site; who either&#xD;
             lives with the subject or sees the subject for ≥2 hours/day ≥4 days/week; and who&#xD;
             agrees to accompany the subject to each study visit and to participate in the&#xD;
             subject's clinical assessments&#xD;
&#xD;
          -  Patients who have a diagnosis of probable mild AD according to Amyloid PET scan at&#xD;
             screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female patients who are pregnant, nursing, or of childbearing potential while not&#xD;
             practicing effective contraception&#xD;
&#xD;
          -  Patients who have signs of delirium&#xD;
&#xD;
          -  Patients who have had a cortical stroke within the preceding 2 years&#xD;
&#xD;
          -  Patients who have a prolonged QTc interval at screening; &gt;450 msec for males or &gt;470&#xD;
             msec for females&#xD;
&#xD;
          -  Patients who have a diagnosis of severe white matter hyperintensity (WMH), which is&#xD;
             defined as ≥25mm of the deep white matter and ≥10mm of the periventricular&#xD;
             capping/banding in lengths&#xD;
&#xD;
          -  Patients who have a diagnosis of dementia or cause of cognitive impairment other than&#xD;
             AD&#xD;
&#xD;
          -  Patients who have a significant abnormal result in laboratory tests, in the opinion of&#xD;
             the investigator&#xD;
&#xD;
          -  Patients who have participated in any investigational drug, stem cell therapy, or&#xD;
             device trial within the previous 3 months at screening&#xD;
&#xD;
          -  Patients with any current psychiatric diagnosis other than AD if, in the judgment of&#xD;
             the investigator, the psychiatric disorder or symptom is likely to confound&#xD;
             interpretation of drug effect, affect cognitive assessments, or affect the subject´s&#xD;
             ability to complete the study&#xD;
&#xD;
          -  Patients who are known to have autosomal dominant mutation-associated presenile AD&#xD;
&#xD;
          -  Patients who show signs of Acquired Immunodeficiency Syndrome (AIDS), Hepatitis B&#xD;
             Virus (HBV), Hepatitis C (HCV), Venereal Disease Research Laboratory (VDRL)&#xD;
&#xD;
          -  Patients who have any conditions that would contraindicate an MRI, such as the&#xD;
             presence metallic objects in the eyes, skin, or heart&#xD;
&#xD;
          -  Patients who have &gt;4 cerebral microhemorrhages (regardless of their anatomical&#xD;
             location or diagnostic characterization as &quot;possible&quot; or &quot;definite&quot;), a single area of&#xD;
             superficial siderosis, or evidence of a prior microhemorrhage as assessed by MRI&#xD;
&#xD;
          -  Patients who have history of malignant cancer within the last 5 years (The following&#xD;
             is a partial list of conditions that are permissible for study entry: non-metastatic&#xD;
             basal and/or squamous cell carcinoma of the skin, in situ cervical, or non-progressive&#xD;
             prostate cancer)&#xD;
&#xD;
          -  Patients who have suspected active lung disease based on chest X-ray&#xD;
&#xD;
          -  Patients who are hypersensitive to fetal bovine serum or penicillin&#xD;
&#xD;
          -  Patients who are currently using immunosuppressants, cytotoxic drug, corticosteroids&#xD;
             or similar steroidal anti-inflammatory medication (e.g., Prednisone) on a regular&#xD;
             basis (exceptions allowed include; regular use of steroidal nasal sprays, topical&#xD;
             steroids, and estrogen-replacement therapy)&#xD;
&#xD;
          -  Patients for whom the investigator judges the liposuction may cause a problem&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Hugh Lee</last_name>
    <phone>301-540-2600</phone>
    <email>hughlee@kcrnresearch.com</email>
  </overall_contact>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>July 17, 2020</study_first_submitted>
  <study_first_submitted_qc>July 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 22, 2020</study_first_posted>
  <last_update_submitted>September 26, 2022</last_update_submitted>
  <last_update_submitted_qc>September 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04482413
org study id: AST-ADP2-US02
nct id: NCT04482413
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a phase 2b randomized, double-blind, Placebo-controlled study with 2 treatment arms,
      to compare the efficacy and safety of AstroStem vs. Placebo treatment in patients with mild
      Alzheimer's Disease(AD). Eligible patients diagnosed with AD within one year of the start of
      treatment will be enrolled. Patients who are randomized into the treatment group will be
      administered via intravenously AstroStem every 4 weeks from Week 0 to Week 36. On the other
      hand, patients who are randomized into the placebo control group will receive Placebo every 4
      weeks from Week 0 to Week 36. After the final administration, patients will be scheduled for
      two follow-up visits, at Weeks 44 and 52, to assess efficacy and safety endpoints.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: SUVR (Standard Uptake Value Ratio)
time frame: Baseline and 52 Weeks
description: Standard Uptake Value Ratio (SUVR) of the Amyloid PET scan
measure: CDR-SB score (Clinical Dementia Rating Sum of Boxes)
time frame: Baseline and 52 Weeks
description: Changes of CDR-SOB from baseline at Week 52 Score range: 0-18.0 0 = normal, 0.5-4.0 = questionable cognitive dementia, 4.5-9.0 = mild dementia, 9.5-15.5 = moderate dementia, and 16.0-18.0 = severe dementia
measure: ADAS-Cog-11 score (Alzheimer's Disease assessment Scale-Cognitive Subscale (11 items))
time frame: Baseline and 52 Weeks
description: Change of ADAS-Cog (Alzheimer's Disease Assessment Scale-cognitive subscale) from Baseline at Week 52 Score range: 0-70 A score of 70 represents the most severe impairment and 0 represents the least impairment
measure: MMSE (Mini-mental status examination)
time frame: Baseline and 52 Weeks
description: Change from baseline to Week 52 in the Mini-mental status examination (MMSE) score. The Mini-Mental State Exam (MMSE) is a widely used test of cognitive function among the elderly; it includes tests of orientation, attention, memory, language and visual-spatial skills. The Mini-Mental State Examination (MMSE) or Folstein test is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment.
measure: ADCS-ADL-MCI (Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory)
time frame: Baseline and 52 Weeks
description: Change from baseline to Week 52 in the ADCS-ADl MCI 0-53 A score of 0 represents the most severe impairment and 53 represents the least impairment
measure: C-SSRS (Columbia Suicide Severity Rating Scale)
time frame: Baseline and 52 Weeks
description: Change from baseline to Week 52 in the Columbia Suicide Severity Rating Scale (C-SSRS) score. The suicidal ideation severity subscale ranges from 1 to 5 (with higher number indicating more severe ideation). The intensity of ideation subscale includes 5 questions each one ranging from 1 to 5 (with higher number indicating more intense ideation). The suicidal behavior subscale includes 4 yes/no questions. The suicidal behavior lethality subscale inquires about the level of actual or potential medical damage.
measure: NPI (Neuropsychiatric Inventory)
time frame: Baseline and 52 Weeks
description: Change from baseline to Week 52 in the Neuropsychiatric Inventory (NPI) score. The NPI is a structured interview with a caregiver or qualified study partner (defined as having direct contact > 2 days/week) that evaluates both presence and severity of 12 neuropsychiatric features which include: delusions, hallucinations, dysphoria, anxiety, agitation/aggression, euphoria, disinhibition, irritability, lability, apathy, aberrant motor behavior, night-time behavior, and appetite/ eating changes. If the response to the domain question is "No", the informant goes to the next question. If "Yes", the informant then rates both the Severity of the symptoms present within the last month on a 3-point scale ranging from 1 to 3 (mild to severe).
measure: Treatment related Adverse Events
time frame: Baseline and 52 Weeks
description: Number of subjects with treatment related adverse events as assessed by analysis of adverse events including symptoms, and abnormal findings on physical examination, vital signs, ECG, and standard laboratory examination results
arm group label: Treatment
arm group type: Experimental
description: Treatment group will be administered via intravenously AstroStem which consists of two syringes and each syringe contains 2.0 x 10^8 cells / 20 mL of saline with 30% auto-serum.
arm group label: Placebo Control
arm group type: Placebo Comparator
description: Placebo control group will receive AstroStem Placebo.
intervention type: Drug
intervention name: AstroStem
description: Treatment group receive AstroStem(Autologous adipose tissue derived mesenchymal stem cells, AdMSCs) every 4 weeks from Week 0 to Week 36.
arm group label: Treatment
intervention type: Drug
intervention name: Placebo
description: Placebo control group receive 20 mL of Saline and auto serum every 4 weeks from Week 0 to Week 36.
arm group label: Placebo Control
other name: AstroStem Placebo
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Hugh Lee
phone: 301-540-2600
email: hughlee@kcrnresearch.com
responsible party type: Sponsor
mesh term: Alzheimer Disease
sharing ipd: Undecided