hCT-MSC in Children With Autism Spectrum Disorder (IMPACT)

A Phase II Study of hCT-MSC, an Umbilical Cord-Derived Mesenchymal Stromal Cell Product, in Children With Autism Spectrum Disorder

The purpose of this Phase II study is to determine the efficacy of human umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC) for improving social communication abilities in children with autism spectrum disorder (ASD).

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorder; Autism
• Intervention / Treatment: Biological: Cord Tissue Mesenchymal Stromal Cells; Other: Placebo Infusion

Detailed Description

The purpose of this double blinded Phase II study is to determine the efficacy of human umbilical cord tissue-derived mesencymal stromal cells (hCT-MSC), administered in two different dosing strategies, in children with autism spectrum disorder (ASD).

This study will be enrolling children with ASD, aging 4-11 years of age. Qualifying subjects will undergo neuropsychological evaluation, EEG testing, eye tracking, CVA assessments, and infusion of study product. Subjects will be randomized to one of two study arms; 1) a single infusion of 6.0x106 cells/Kg at baseline, followed by a blinded placebo infusion at six months or, 2) Placebo infusion at baseline, followed by an intravenous dose of 6x106 cells/Kg at six months.

The primary endpoint of this study is the change in social communication skill from baseline to six months. The potential risks associated with infusion of MSCs include a reaction to the product (rash, shortness of breath, wheezing, difficulty breathing, hypotension, swelling around the mouth, throat or eyes, tachycardia, diaphoresis), transmission of infection, and HLA sensitization.

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 11 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Age ≥ 4 years to < 12 years (11 years, 364 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 Brief Observation of Symptoms of Autism (BOSA) and the Autism Diagnostic Interview-Revised (ADI-R)
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 psychiatric medication regimen (dose and dosing schedule) for at least 2 months prior to infusion of study product
5. Normal absolute lymphocyte count (≥1200/uL for African American participants and ≥1500/uL for all other participants)
6. GAI ≥ 65 via cognitive testing by study personnel
7. Participant and parent/guardian are English speaking
8. Able to travel to Duke University two times (baseline, six months), and parent/guardian is able to participate in interim surveys and interviews
9. Parental/guardian consent from at least one parent/guardian

Exclusion Criteria

1. General:

   1. Review of medical records and/or screening assessments indicates ASD diagnosis and/or GAI > 65 not confident
   2. Known diagnosis of any of the following coexisting psychiatric conditions: depression, bipolar disorder, schizophrenia, obsessive compulsive disorder associated with bipolar disorder, Tourette syndrome
   3. Screening data suggests that participant would not be able to comply with the requirements of the study procedures as assessed by the study team
   4. Family is unwilling or unable to commit to participation in all study-related assessments, including protocol follow up
   5. Sibling is enrolled in this (Duke IMPACT) 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 defect definitively 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. Exposure to COVID-19 in the preceding 14 days or positive COVID-19 test in the previous 28 days. Subjects with a past history of infection with COVID-19 must be symptom-free for 14 days prior to the initial visit.

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, Platelets <150 x 10e9/uL, WBC <3,000 cells/mL, ALC <1200/uL for African Americans or <1500/uL for all other participants.
   12. Evidence of clinically relevant physical dysmorphology indicative of a genetic syndrome as assessed by the PIs or other investigators, including a medical geneticist and psychiatrists trained in identifying dysmorphic features associated with neurodevelopmental conditions.

5. Current/Prior Therapy:

   a. Availability of a banked, qualified autologous cord blood unit or parents deferred use of qualified, autologous cord blood unit b. History of prior cell therapy c. Current or prior use of IVIG or other anti-inflammatory medications with the exception of NSAIDs d. 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MSC; One dose of 6x10e6 cells/kg administered intravenously.	Biological: Cord Tissue Mesenchymal Stromal Cells; Human Umbilical Cord Tissue Derived Mesenchymal Stromal Cells (hCT-MSC), isolated and expanded from umbilical cord tissue from allogeneic unrelated donors. One dose of 6x10e6 cells/kg administered intravenously.
Placebo Comparator: Placebo Infusion; Placebo infusion	Other: Placebo Infusion; Placebo comparative infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change on the Socialization and Communication Subscale Standard Scores on the Vineland Behavior Scales	The primary outcome measure is the mean of the change on the Socialization and Communication Subscale Standard Scores on the Vineland Adaptive Behavior Scales (VABS-3). The primary endpoint is the change on this outcome measure from baseline to six months.	Baseline, 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in VABS-3 Socialization Standard Score	Change in VABS-3 (Vineland Adaptive Behavior Scales) Socialization Standard Score	Baseline, 6 months
Change in VABS-3 Communication Standard Score	Change in VABS-3 (Vineland Adaptive Behavior Scales) Communication Standard Score	Baseline, 6 months
Change in CGI-Severity score	Clinical Global Impression- Severity Scale	Baseline, 6 months
CGI-Intervention score	Clinical Global Impression- Impression	Baseline, 6 months
Change in the Pediatric Quality of Life Scale	Pediatric Quality of Life Scale, raw scale range of 0-2300 with higher scores indicating a higher quality of life (better outcome)	Baseline, 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of infusion reactions	Assess for infusion reactions	Baseline, 6 months
Incidence and severity of product-related infections	Assess for infections directly related to the study product infusions	Baseline, 6 months
Evidence of formation of anti-HLA antibodies	Assess for anti-HLA antibodies	Baseline, 6 months, 12 months
Incidence and severity of graft versus host disease	Assess for signs and symptoms of graft versus host disease	6 months, 12 months
Incidence and severity of unexpected adverse events related to the study product	Assess for study related and unexpected adverse events	Baseline, 6 months, 12 months

Collaborators and Investigators

• Sponsor: Joanne Kurtzberg, MD
• Collaborators: The Marcus Foundation; Cryo-Cell International
• Investigators: Principal Investigator: Lauren Franz, MBChB, Duke University; Principal Investigator: Beth Shaz, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2020
• Primary Completion (Actual): May 2, 2023
• Study Completion (Actual): February 1, 2024

Study Registration Dates

• First Submitted: September 12, 2019
• First Submitted That Met QC Criteria: September 12, 2019
• First Posted (Actual): September 13, 2019

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Autism; Autism Spectrum Disorder; Stem cell; Mesenchymal Stromal Cells
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
• Other Study ID Numbers: Pro00113011; Pro00102894 (Other Identifier: Duke IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No