Open Label Phase I hCT-MSC in Toddlers With Autism Spectrum Disorder

NCT04294290 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: Pro00104460
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single site, prospective study of one intravenous infusion of human umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC) in toddlers with autism spectrum disorder (ASD). Toddlers 18 to 48 months of age with a confirmed diagnosis of ASD will be eligible to participate. Diagnosis will be confirmed at the time of the eligibility visit at the Duke Center for Autism and Brain Development. All participants will receive a single intravenous dose of 2x106/kg hCT-MSC per kilogram at baseline. Assessments will be conducted at baseline and 6 months, with remote follow-up assessments at 12 months.

Conditions

Autism Spectrum Disorder

Keywords

Autism Spectrum Disorder; ASD; Autism; PDD

Outcome Measures

Primary Outcomes (15)

• Safety of hCT-MSC Infusion as Measured by Total Number of Infusion Reactions

  1 year

• Safety of hCT-MSC Infusion as Measured by Severity of Infusion Reactions

  CTCAE is used to measure severity: 1= Mild, 2 = Moderate, 3 = Severe, 4 = Life-threatening, 5 = Death.

  1 year

• Safety of hCT-MSC Infusion as Measured by Total Number of Product-related Infections

  1 year

• Safety of hCT-MSC Infusion as Measured by Severity of Product-related Infections

  CTCAE is used to measure severity: 1= Mild, 2 = Moderate, 3 = Severe, 4 = Life-threatening, 5 = Death.

  1 year

• Safety of hCT-MSC Infusion as Measured by Number of Participants With Evidence of Alloimmunization Via Anti-HLA Antibodies

  1 year

• Safety of hCT-MSC Infusion as Measured by Total Number of Graft vs. Host Disease (GVHD) Instances

  1 year

• Safety of hCT-MSC Infusion as Measured by Severity of Graft vs. Host Disease (GVHD)

  CTCAE is used to measure severity: 1= Mild, 2 = Moderate, 3 = Severe, 4 = Life-threatening, 5 = Death.

  1 year

• Safety of hCT-MSC Infusion as Measured by Total Number of Unexpected Adverse Events

  1 year

• Safety of hCT-MSC Infusion as Measured by Severity of Unexpected Adverse Events

  CTCAE is used to measure severity: 1= Mild, 2 = Moderate, 3 = Severe, 4 = Life-threatening, 5 = Death.

  1 year

• Change in Pervasive Developmental Disorder Behavior Inventory Autism Composite Score (PDDBI)

  6-month T score minus Baseline T score. PDDBI is designed to assess problem behaviors and social, language, and learning or memory skills of children who have been diagnosed with autism spectrum disorder. Raw scores are converted to T scores with a mean of 50 and standard deviation of 10, with a possible range of 10-100. Higher scores represent more severe problem behaviors. Therefore, a negative change in score indicates improvement.

  Baseline, 6 months

• Change in VABS-3 (Vineland Adaptive Behavior Scales) Socialization and Communication Composite Score

  The change in the average of the Communication and Socialization Standard Subscale Scores on the Vineland Adaptive Behavior Scales (VABS-3) from the Comprehensive Interview form from baseline to six months. Higher scores indicate greater communication and/or socialization, with a range of 20 to 160 (mean = 100). A positive change in the scores indicates an improvement in communication and/or socialization.

  Baseline, 6 months

• Number of Participants Who Improved (Much Improved or Minimally Improved) on the Clinical Global Impression Scale (CGI)

  The number of participants who scored a 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the Clinical Global Impression Scale (CGI-I). The CGI-I score ranges from 1 to 7, where a lower score indicates greater improvement.

  Baseline, 6 months

• Change in Communicative Development Inventories (CDI-2)

  6-month number of words produced minus baseline number of words produced. A positive change indicates improvement.

  Baseline, 6 months

• Change in Attention Abilities as Assessed Via Eye-tracking

  6-month percentage of gaze directed towards social stimulus minus baseline percentage of gaze directed towards social stimulus. A negative change indicates improvement.

  Baseline, 6 months

• Change in Brain Activity as Measured by EEG

  Baseline, 6 months

Study Arms (1)

hCT-MSC infusion

EXPERIMENTAL

hCT-MSC infusion

Biological: hCT-MSC infusion

Interventions

hCT-MSC infusion BIOLOGICAL

This is a single site, phase I, open-label, prospective study of one intravenous infusion of human umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC) in 12 toddlers 18 to 48 months of age with autism spectrum disorder (ASD).

hCT-MSC infusion

Eligibility Criteria

• Age: 18 Months - 48 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age ≥ 18 months to ≤ 48 months (48 months, 29 days) at the time of consent
• Confirmed clinical DSM-5 diagnosis of Autism Spectrum Disorder using the DSM-5 Checklist as informed by the Autism Diagnostic Observation Schedule - 2.
• Fragile X testing performed and negative; CMA and/or whole exome sequencing performed and results not linked to autism diagnosis
• Stable on current psychoactive medication regimen (dose and dosing schedule) for at least 2 months prior to infusion of study product
• Normal absolute lymphocyte count (≥1500/uL)
• Participant and parent/guardian are English speaking
• Able to travel to Duke University for two multi-day visits (baseline and six months) and parent/guardian is able to participate in interim surveys and interviews
• Parental consent

You may not qualify if:

• General:
• Review of medical records indicates ASD diagnosis not likely
• Screening data suggests that participant would not be able to comply with the requirements of the study procedures as assessed by the study team
• Family is unwilling or unable to commit to participation in all study-related assessments, including protocol follow up
• Sibling is enrolled in this (Duke hCT-MSC) study
• Genetic:
• Records indicate that child has a known genetic syndrome such as (but not limited to) Fragile X syndrome, neurofibromatosis, Rett syndrome, tuberous sclerosis, PTEN mutation, cystic fibrosis, muscular dystrophy or a genetic mutation known to be associated with ASD
• Known pathogenic mutation or copy number variation (CNV) associated with ASD (e.g., 16p11.2, 15q13.2, 2q13.3)
• Infectious:
• Known active CNS infection
• Evidence of uncontrolled infection based on records or clinical assessment
• Known HIV positivity
• Medical:
• Known metabolic disorder
• Known mitochondrial dysfunction

Sponsors & Collaborators

• Duke University: lead
• The Marcus Foundation: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Autism Spectrum Disorder; Autistic Disorder

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Results Point of Contact

• Title: Joanne Kurtzberg, MD
• Organization: Duke University

joanne.kurtzberg@duke.edu

919-668-1119

Study Officials

• Joanne Kurtzberg, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

• Geraldine Dawson, PhD

  Duke Health

  PRINCIPAL INVESTIGATOR

• Jessica Sun, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Jerome Harris Distinguished Professor of Pediatrics

Study Record Dates

• First Submitted: March 2, 2020
• First Posted: March 4, 2020
• Study Start: February 24, 2021
• Primary Completion: August 17, 2022
• Study Completion: August 17, 2022
• Last Updated: February 24, 2025
• Results First Posted: February 24, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)