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

Phase 1

Completed

• Conditions: Autism Spectrum Disorder
• Interventions: Biological: hCT-MSC infusion

• Registration Number: NCT04294290
• Lead Sponsor: Duke University

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.

Detailed Description

The primary purpose of this study is to evaluate safety and feasibility. Safety assessments include monitoring of acute infusion reactions, adverse events, incidence of infections, and markers of alloimmunization. Clinical outcome measures will also be described. A key clinical outcome measeure is the change in social communication abilities from baseline to 6 months based on the Joint Engagement Rating Inventory (JERI), a commonly-used and well-validated coding system for rating the quality and quantity of social communication skills in toddlers with and without ASD.91 JERI coding rates social communication abilities on a 1 to 7 scale and factors in both the quantity and quality of skills. The total joint engagement score as well as ratings on all JERI subscales that comprise the total score will be described.

Other clinical endpoints will include the PDD Behavior Inventory (PDDBI) autism composite score, the mean of the Socialization Subscale Standard Score and Communication Subscale Standard Score on the Vineland Adaptive Behavior Scales (VABS-3), the Clinical Global Impression Scale (CGI) - Severity and Improvement Scales, the Communicative Development Inventories (CDI-2): Words \& Sentences subscales, attention abilities via eye-tracking, and brain activity.

Exploratory clinical endpoints will include autism symptoms measured by an app that elicits and records autism symptoms on an iPad (SenseToKnow), Autism Diagnostic Observation Scale (ADOS-2) Calibrated Severity Score (overall, social affect, and repetitive behavior), PDD Behavior Inventory (PDDBI) Subscales, and VABS-3 Standard Score and age equivalent for the following subscales: Socialization, Communication, and Daily Living and the Standard Score and age equivalent for the VABS-3 Adaptive Behavior Composite.

Safety and VABS-3 assessments will also be conducted remotely at three and 12 months. Duration of study participation will be 12 months from the time of the baseline infusion.

Study Timeline

• Study First Submitted: 2020-03-02
• Study First Submitted QC: 2020-03-02
• Study First Posted: 2020-03-04
• Study Start: 2021-02-24
• Primary Completion: 2022-08-17
• Study Completion: 2022-08-17
• Results First Submitted: 2024-02-16
• Status Verified: 2025-02
• Results First Submitted QC: 2025-02-03
• Last Update Submitted: 2025-02-03
• Results First Posted: 2025-02-24
• Last Update Posted: 2025-02-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1. Age ≥ 18 months to ≤ 48 months (48 months, 29 days) at the time of consent
2. Confirmed clinical DSM-5 diagnosis of Autism Spectrum Disorder using the DSM-5 Checklist as informed by the Autism Diagnostic Observation Schedule - 2.
3. Fragile X testing performed and negative; CMA and/or whole exome sequencing performed and results not linked to autism diagnosis
4. Stable on current psychoactive medication regimen (dose and dosing schedule) for at least 2 months prior to infusion of study product
5. Normal absolute lymphocyte count (≥1500/uL)
6. Participant and parent/guardian are English speaking
7. 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
8. Parental consent

Exclusion Criteria

1. General:

   1. Review of medical records indicates ASD diagnosis not likely
   2. Screening data suggests that participant would not be able to comply with the requirements of the study procedures as assessed by the study team
   3. Family is unwilling or unable to commit to participation in all study-related assessments, including protocol follow up
   4. Sibling is enrolled in this (Duke hCT-MSC) study

2. Genetic:

   1. 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
   2. Known pathogenic mutation or copy number variation (CNV) associated with ASD (e.g., 16p11.2, 15q13.2, 2q13.3)

3. Infectious:

   1. Known active CNS infection
   2. Evidence of uncontrolled infection based on records or clinical assessment
   3. Known HIV positivity

4. Medical:

   1. Known metabolic disorder
   2. Known mitochondrial dysfunction
   3. History of unstable epilepsy or uncontrolled seizure disorder, infantile spasms, Lennox Gastaut syndrome, Dravet syndrome, or other similar chronic seizure disorder
   4. Active malignancy or prior malignancy that was treated with chemotherapy
   5. History of a primary immunodeficiency disorder
   6. History of autoimmune cytopenias (i.e., ITP, AIHA)
   7. Coexisting medical condition that would place the child at increased risk for complications of study procedures
   8. Concurrent genetic or acquired disease or comorbidity(ies) that could require a future stem cell transplant
   9. Significant sensory (e.g., blindness, deafness, uncorrected hearing impairment) or motor (e.g., cerebral palsy) impairment
   10. Impaired renal or liver function as determined by serum creatinine >1.5mg/dL or total bilirubin >1.3mg/dL, except in patients with known Gilbert's disease
   11. Significant hematologic abnormalities defined as: Hemoglobin <10.0 g/dL, WBC < 3,000 cells/mL, ALC <1000/uL, Platelets <150 x 10e9/uL
   12. Known clinically relevant physical dysmorphology associated with neurodevelopmental conditions.

5. Current/Prior Therapy:

   a. History of prior cell therapy b. Current or prior use of IVIG or other anti-inflammatory medications with the exception of NSAIDs c. Current or prior immunosuppressive therapy i. No systemic steroid therapy that has lasted >2 weeks, and no systemic steroids within 3 months prior to enrollment. Topical and inhaled steroids are permitted.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
hCT-MSC infusion	hCT-MSC infusion	-
hCT-MSC infusion	hCT-MSC infusion	hCT-MSC infusion

Primary Outcome Measures

Name	Time	Method
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	1 year	CTCAE is used to measure severity: 1= Mild, 2 = Moderate, 3 = Severe, 4 = Life-threatening, 5 = Death.
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	1 year	CTCAE is used to measure severity: 1= Mild, 2 = Moderate, 3 = Severe, 4 = Life-threatening, 5 = Death.
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)	1 year	CTCAE is used to measure severity: 1= Mild, 2 = Moderate, 3 = Severe, 4 = Life-threatening, 5 = Death.
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	1 year	CTCAE is used to measure severity: 1= Mild, 2 = Moderate, 3 = Severe, 4 = Life-threatening, 5 = Death.
Change in Pervasive Developmental Disorder Behavior Inventory Autism Composite Score (PDDBI)	Baseline, 6 months	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.
Change in VABS-3 (Vineland Adaptive Behavior Scales) Socialization and Communication Composite Score	Baseline, 6 months	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.
Number of Participants Who Improved (Much Improved or Minimally Improved) on the Clinical Global Impression Scale (CGI)	Baseline, 6 months	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.
Change in Communicative Development Inventories (CDI-2)	Baseline, 6 months	6-month number of words produced minus baseline number of words produced. A positive change indicates improvement.
Change in Attention Abilities as Assessed Via Eye-tracking	Baseline, 6 months	6-month percentage of gaze directed towards social stimulus minus baseline percentage of gaze directed towards social stimulus. A negative change indicates improvement.
Change in Brain Activity as Measured by EEG	Baseline, 6 months

Trial Locations

Locations (1)

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States