<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/NCT04484077</url>
  </required_header>
  <id_info>
    <org_study_id>PRO00104691</org_study_id>
    <nct_id>NCT04484077</nct_id>
  </id_info>
  <brief_title>hCT-MSC Infusion in Adults With Autism Spectrum Disorder</brief_title>
  <acronym>AIMs</acronym>
  <official_title>A PHASE I STUDY OF hCT-MSC, AN UMBILICAL CORD-DERIVED MESENCHYMAL STROMAL CELL PRODUCT, IN ADULTS WITH AUTISM SPECTRUM DISORDER</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Joanne Kurtzberg, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Marcus Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The purpose of the study is to determine the safety and tolerability of a single intravenous&#xD;
      dose of Human Umbilical Cord Tissue Derived Mesenchymal Stromal Cells (hCT-MSC) in adults&#xD;
      with autism spectrum disorder (ASD). hCT-MSC is a cell product isolated from umbilical cord&#xD;
      tissue. The cells from the cord tissue are processed and expanded in the laboratory and then&#xD;
      infused intravenously in a single dose per participant. Participants will be ages 18-35&#xD;
      years, with ASD and a full-scale IQ &gt;70 without an identified genetic cause of autism.&#xD;
      Participants will have an in-person baseline visit and remote follow up visits at 6 and 12&#xD;
      months. In addition to the primary endpoints evaluating safety, the study will evaluate&#xD;
      changes in social communications skills after hCT-MSC administration.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, open label, phase one study to determine the safety and tolerability&#xD;
      of a single intravenous dose of Human Umbilical Cord Tissue Derived Mesenchymal Stromal Cells&#xD;
      (hCT-MSC) in adults with autism spectrum disorder (ASD). hCT-MSCs are manufactured from&#xD;
      umbilical cord tissue donated by healthy mothers delivering full term babies via Cesarean&#xD;
      Section. The cells are extracted from the cord tissue, expanded and cryopreserved (frozen).&#xD;
      One dose of 2x10^6 cells/kg (maximum of 10 x 10^7) will be administered intravenously to each&#xD;
      participant in this study.&#xD;
&#xD;
      It is hypothesized that immune dysregulation and/or abnormal neuronal connectivity that&#xD;
      adversely affects normal brain development may cause core symptomatology observed in&#xD;
      individuals with ASD. Mesenchymal stromal cells (MSC) have demonstrated a multitude of&#xD;
      immunomodulatory effects which are thought to be carried out via paracrine and trophic&#xD;
      signaling. While MSCs modulate the immune response, MSCs themselves have low immunogenicity&#xD;
      (the body does not have a strong immune reaction against them) and they do not permanently&#xD;
      engraft in the recipient.&#xD;
&#xD;
      Adults ages 18 to less than 35 years with ASD will be eligible to participate. All&#xD;
      participants will have a screening visit that includes clinical evaluations to verify&#xD;
      cognitive abilities and confirmation of eligibility.&#xD;
&#xD;
      One dose of 2x10^6 cells/kg (maximum of 10 x 10^7) will be administered intravenously to each&#xD;
      participant at a baseline visit. Participants will be admitted to the infusion center on the&#xD;
      day of their baseline visit and vital signs (heart rate, blood pressure, temperature,&#xD;
      respiratory rate) will be measured. Participants may request anti-anxiety medication prior to&#xD;
      IV placement if desired. A peripheral IV will be placed and prior to the infusion,&#xD;
      premedications (Benadryl, Solumedrol, 0.5mg/kg each) will be administered. The hCT-MSCs&#xD;
      product will be administered intravenously over 30-60 minutes. Pulse oximetry will be&#xD;
      monitored continuously throughout the infusion and IV fluid maintenance will be given.&#xD;
      Participants will be discharged after 1 hour, providing all vital signs are at their baseline&#xD;
      and they are asymptomatic with no evidence of toxicity. Participants will be evaluated the&#xD;
      day after the infusion to assess for any infusion-related adverse reactions or complications.&#xD;
      A phone call or email will be done to assess safety of the infusion 7-10 days after the&#xD;
      infusion. Remote follow up will be conducted 6 months and one year after infusion. The&#xD;
      Medical and Behavioral History Questionnaire assessing adverse events will be obtained at&#xD;
      baseline, 6 and 12-months.&#xD;
&#xD;
      The main endpoint is safety, and acute infusion reactions, incidence of infections, and&#xD;
      markers of alloimmunization will be assessed. Social communication will be assessed at&#xD;
      baseline and 6 months post product administration.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 24, 2022</start_date>
  <completion_date type="Anticipated">May 2024</completion_date>
  <primary_completion_date type="Anticipated">November 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of infusion reactions</measure>
    <time_frame>Baseline through 10 days post infusion</time_frame>
    <description>cumulative incidence as measured by clinical examination and patient interview</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of product-related infections</measure>
    <time_frame>Baseline through 12 months</time_frame>
    <description>cumulative incidence as measured by patient interview and questionnaire</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Evidence of formation of anti-HLA antibodies</measure>
    <time_frame>Baseline, 6 months, 12 months</time_frame>
    <description>change from baseline to 6 and 12 months post infusion as measured by PRA testing</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of graft vs. host disease</measure>
    <time_frame>Baseline through 12 months</time_frame>
    <description>cumulative incidence as measured by patient interview and questionnaire</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of unexpected adverse events, by severity and relation to study</measure>
    <time_frame>Baseline through 12 months</time_frame>
    <description>cumulative incidence as measured by patient questionnaire and clinical labs</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Vineland Adaptive Behavior Scale Interview, 3rd Edition, Comprehensive interview form</measure>
    <time_frame>Baseline and 6 months</time_frame>
    <description>Change from baseline to six months in the Combined Socialization Standard Score based on parent report. Scores range from 20 to 140. Higher scores indicate a higher functioning level</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">11</enrollment>
  <condition>Autism Spectrum Disorder</condition>
  <condition>Autism</condition>
  <arm_group>
    <arm_group_label>hCT-MSC infusion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single, intravenous infusion of hCT-MSCs. Targeted dose is 2x10^6 cells/kg with a maximum dose of 10 x 10^7 cells/kg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>hCT-MSC</intervention_name>
    <description>2x10^6 hCT-MSC/kg suspended in plasmalyte-A, 5% HSA, and residual DMSO/dextran administered intravenously over 30-60 minutes via syringe pump</description>
    <arm_group_label>hCT-MSC infusion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥18 to &lt; 35 years (34 years, 364 days) at the time of consent&#xD;
&#xD;
          2. Confirmed pre-existing diagnosis of ASD in the individual's educational and/or medical&#xD;
             record&#xD;
&#xD;
          3. Fragile X testing performed and negative; CMA and/or whole exome sequencing performed&#xD;
             and results not linked to autism diagnosis&#xD;
&#xD;
          4. Stable on current psychiatric medication regimen (dose and dosing schedule) for at&#xD;
             least 2 months prior to infusion of study product, with no intention of changing or&#xD;
             beginning new psychiatric medications or behavioral treatments during the duration of&#xD;
             the study.&#xD;
&#xD;
          5. Normal absolute lymphocyte count (≥1200/uL for African American participants and&#xD;
             ≥1500/uL for all other participants)&#xD;
&#xD;
          6. General Ability Index of ≥70, confirmed through cognitive testing completed by study&#xD;
             personnel to establish eligibility&#xD;
&#xD;
          7. Participant and Parent are English speaking&#xD;
&#xD;
          8. Able to travel to Duke University for baseline visit.&#xD;
&#xD;
          9. Participant has a parent who spends four or more hours a week with the participant,&#xD;
             who is able and willing to participate in study visits and interim surveys and&#xD;
             interviews&#xD;
&#xD;
         10. Informed consent of the participant and parent (participants must have legal authority&#xD;
             regarding their own medical care and a parent or legally authorized representative may&#xD;
             not consent on their behalf)&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. General:&#xD;
&#xD;
               1. Review of medical records indicates ASD diagnosis and IQ &gt; 70 unlikely.&#xD;
&#xD;
               2. Known or suspected diagnosis of any of the following coexisting psychiatric&#xD;
                  conditions: bipolar disorder, schizophrenia, Tourette syndrome, and/or any&#xD;
                  co-occurring psychiatric disorder that the investigator believes would interfere&#xD;
                  with accurate completion of study instruments and/or current (within the past&#xD;
                  year) evidence of suicidality as assessed by an interview with participant and/or&#xD;
                  parent which includes the Columbia Suicide Severity Rating Scale, and a review of&#xD;
                  responses on the Behavioral and Symptom Identification Scale (BASIS-24).&#xD;
&#xD;
               3. Screening data or in-person evaluations suggest that participant would not be&#xD;
                  able to comply with the requirements of the study procedures as assessed by the&#xD;
                  study team&#xD;
&#xD;
               4. Parent and/or participant is unwilling or unable to commit to participation in&#xD;
                  all study-related assessments, including protocol follow up&#xD;
&#xD;
               5. Sibling is enrolled in this (Duke AIMs) study&#xD;
&#xD;
          2. Genetic:&#xD;
&#xD;
               1. Records indicate that the participant has a known genetic syndrome such as (but&#xD;
                  not limited to) Fragile X syndrome, neurofibromatosis, Rett syndrome, tuberous&#xD;
                  sclerosis, PTEN mutation, cystic fibrosis, muscular dystrophy or a genetic defect&#xD;
                  definitively known to be associated with ASD&#xD;
&#xD;
               2. Known pathogenic mutation or copy number variation (CNV) associated with ASD&#xD;
                  (e.g., 16p11.2, 15q13.2, 2q13.3)&#xD;
&#xD;
          3. Infectious:&#xD;
&#xD;
               1. Known active CNS infection&#xD;
&#xD;
               2. Evidence of uncontrolled infection based on records or clinical assessment&#xD;
&#xD;
               3. Known HIV positivity&#xD;
&#xD;
               4. Exposure to COVID-19 in the preceding 14 days or positive COVID-19 test in the&#xD;
                  previous 28 days. Subjects with a past history of infection with COVID-19 must be&#xD;
                  symptom-free for 14 days prior to the initial visit.&#xD;
&#xD;
          4. Medical:&#xD;
&#xD;
               1. Known metabolic disorder&#xD;
&#xD;
               2. Known mitochondrial dysfunction&#xD;
&#xD;
               3. History of unstable epilepsy or uncontrolled seizure disorder, infantile spasms,&#xD;
                  Lennox Gastaut syndrome, Dravet syndrome, or other similar chronic seizure&#xD;
                  disorder&#xD;
&#xD;
               4. Active malignancy or prior malignancy that was treated with chemotherapy&#xD;
&#xD;
               5. History of a primary immunodeficiency disorder&#xD;
&#xD;
               6. History of autoimmune cytopenias (i.e., ITP, AIHA)&#xD;
&#xD;
               7. Coexisting medical condition that would place the participant at increased risk&#xD;
                  for complications of study procedures&#xD;
&#xD;
               8. Concurrent genetic or acquired disease or comorbidity(ies) that could require a&#xD;
                  future stem cell transplant&#xD;
&#xD;
               9. Significant sensory (e.g., blindness, deafness, uncorrected hearing impairment)&#xD;
                  or motor (e.g., cerebral palsy) impairment&#xD;
&#xD;
              10. Impaired renal or liver function as determined by serum creatinine &gt;1.5mg/dL or&#xD;
                  total bilirubin &gt;1.3mg/dL, except in participants with known Gilbert's disease&#xD;
&#xD;
              11. Significant hematologic abnormalities defined as: Hemoglobin &lt;10.0 g/dL,&#xD;
                  Platelets &lt;150 x 10e9/uL, WBC &lt;3,000 cells/mL, ALC &lt;1200/uL for African Americans&#xD;
                  or &lt;1500/uL for all other participants.&#xD;
&#xD;
              12. Evidence of clinically relevant physical dysmorphology indicative of a genetic&#xD;
                  syndrome as assessed by the PIs or other investigators, including a medical&#xD;
                  geneticist and psychiatrists trained in identifying dysmorphic features&#xD;
                  associated with neurodevelopmental conditions.&#xD;
&#xD;
              13. Current pregnancy and unwillingness to use adequate birth control for 3 months&#xD;
                  after the final study product infusion.&#xD;
&#xD;
          5. Current/Prior Therapy:&#xD;
&#xD;
             a. Availability of a banked, qualified autologous cord blood unit or parent deferred&#xD;
             use of qualified, autologous cord blood unit b. History of prior cell therapy c.&#xD;
             Current or prior use of IVIG or other anti-inflammatory medications with the exception&#xD;
             of NSAIDs d. Current or prior immunosuppressive therapy i. No systemic steroid therapy&#xD;
             that has lasted &gt;5 days within 4 weeks, prior to enrollment. Topical and inhaled&#xD;
             steroids are permitted.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>34 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jessica Sun, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Joanne Kurtzberg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 16, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 23, 2020</study_first_posted>
  <last_update_submitted>May 23, 2023</last_update_submitted>
  <last_update_submitted_qc>May 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 24, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Duke University</investigator_affiliation>
    <investigator_full_name>Joanne Kurtzberg, MD</investigator_full_name>
    <investigator_title>Jerome Harris Distinguished Professor of Pediatrics; Professor of Pathology; Director, Marcus Center for Cellular Cures; Director, Pediatric Blood and Marrow Transplant Program; Director, Carolinas Cord Blood Bank</investigator_title>
  </responsible_party>
  <keyword>autism</keyword>
  <keyword>MSC</keyword>
  <keyword>hCT-MSC</keyword>
  <keyword>mesenchymal stromal cells</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Autistic Disorder</mesh_term>
    <mesh_term>Autism Spectrum Disorder</mesh_term>
    <mesh_term>Child Development Disorders, Pervasive</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT04484077
org study id: PRO00104691
nct id: NCT04484077
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of the study is to determine the safety and tolerability of a single intravenous
      dose of Human Umbilical Cord Tissue Derived Mesenchymal Stromal Cells (hCT-MSC) in adults
      with autism spectrum disorder (ASD). hCT-MSC is a cell product isolated from umbilical cord
      tissue. The cells from the cord tissue are processed and expanded in the laboratory and then
      infused intravenously in a single dose per participant. Participants will be ages 18-35
      years, with ASD and a full-scale IQ >70 without an identified genetic cause of autism.
      Participants will have an in-person baseline visit and remote follow up visits at 6 and 12
      months. In addition to the primary endpoints evaluating safety, the study will evaluate
      changes in social communications skills after hCT-MSC administration.
This is a prospective, open label, phase one study to determine the safety and tolerability
      of a single intravenous dose of Human Umbilical Cord Tissue Derived Mesenchymal Stromal Cells
      (hCT-MSC) in adults with autism spectrum disorder (ASD). hCT-MSCs are manufactured from
      umbilical cord tissue donated by healthy mothers delivering full term babies via Cesarean
      Section. The cells are extracted from the cord tissue, expanded and cryopreserved (frozen).
      One dose of 2x10^6 cells/kg (maximum of 10 x 10^7) will be administered intravenously to each
      participant in this study.

      It is hypothesized that immune dysregulation and/or abnormal neuronal connectivity that
      adversely affects normal brain development may cause core symptomatology observed in
      individuals with ASD. Mesenchymal stromal cells (MSC) have demonstrated a multitude of
      immunomodulatory effects which are thought to be carried out via paracrine and trophic
      signaling. While MSCs modulate the immune response, MSCs themselves have low immunogenicity
      (the body does not have a strong immune reaction against them) and they do not permanently
      engraft in the recipient.

      Adults ages 18 to less than 35 years with ASD will be eligible to participate. All
      participants will have a screening visit that includes clinical evaluations to verify
      cognitive abilities and confirmation of eligibility.

      One dose of 2x10^6 cells/kg (maximum of 10 x 10^7) will be administered intravenously to each
      participant at a baseline visit. Participants will be admitted to the infusion center on the
      day of their baseline visit and vital signs (heart rate, blood pressure, temperature,
      respiratory rate) will be measured. Participants may request anti-anxiety medication prior to
      IV placement if desired. A peripheral IV will be placed and prior to the infusion,
      premedications (Benadryl, Solumedrol, 0.5mg/kg each) will be administered. The hCT-MSCs
      product will be administered intravenously over 30-60 minutes. Pulse oximetry will be
      monitored continuously throughout the infusion and IV fluid maintenance will be given.
      Participants will be discharged after 1 hour, providing all vital signs are at their baseline
      and they are asymptomatic with no evidence of toxicity. Participants will be evaluated the
      day after the infusion to assess for any infusion-related adverse reactions or complications.
      A phone call or email will be done to assess safety of the infusion 7-10 days after the
      infusion. Remote follow up will be conducted 6 months and one year after infusion. The
      Medical and Behavioral History Questionnaire assessing adverse events will be obtained at
      baseline, 6 and 12-months.

      The main endpoint is safety, and acute infusion reactions, incidence of infections, and
      markers of alloimmunization will be assessed. Social communication will be assessed at
      baseline and 6 months post product administration.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of infusion reactions
time frame: Baseline through 10 days post infusion
description: cumulative incidence as measured by clinical examination and patient interview
measure: Incidence of product-related infections
time frame: Baseline through 12 months
description: cumulative incidence as measured by patient interview and questionnaire
measure: Evidence of formation of anti-HLA antibodies
time frame: Baseline, 6 months, 12 months
description: change from baseline to 6 and 12 months post infusion as measured by PRA testing
measure: Incidence of graft vs. host disease
time frame: Baseline through 12 months
description: cumulative incidence as measured by patient interview and questionnaire
measure: Incidence of unexpected adverse events, by severity and relation to study
time frame: Baseline through 12 months
description: cumulative incidence as measured by patient questionnaire and clinical labs
measure: The Vineland Adaptive Behavior Scale Interview, 3rd Edition, Comprehensive interview form
time frame: Baseline and 6 months
description: Change from baseline to six months in the Combined Socialization Standard Score based on parent report. Scores range from 20 to 140. Higher scores indicate a higher functioning level
arm group label: hCT-MSC infusion
arm group type: Experimental
description: A single, intravenous infusion of hCT-MSCs. Targeted dose is 2x10^6 cells/kg with a maximum dose of 10 x 10^7 cells/kg.
intervention type: Biological
intervention name: hCT-MSC
description: 2x10^6 hCT-MSC/kg suspended in plasmalyte-A, 5% HSA, and residual DMSO/dextran administered intravenously over 30-60 minutes via syringe pump
arm group label: hCT-MSC infusion
criteria: 
gender: All
minimum age: 18 Years
maximum age: 34 Years
healthy volunteers: No
last name: Jessica Sun, MD
role: Principal Investigator
affiliation: Duke University
last name: Joanne Kurtzberg, MD
role: Principal Investigator
affiliation: Duke University
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Duke University
investigator full name: Joanne Kurtzberg, MD
investigator title: Jerome Harris Distinguished Professor of Pediatrics; Professor of Pathology; Director, Marcus Center for Cellular Cures; Director, Pediatric Blood and Marrow Transplant Program; Director, Carolinas Cord Blood Bank
mesh term: Autistic Disorder
mesh term: Autism Spectrum Disorder
mesh term: Child Development Disorders, Pervasive
sharing ipd: No