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

Autism Spectrum Disorder Clinical Trial

— TACT  

Official title:

AN OPEN LABEL PHASE I STUDY OF hCT-MSC, AN UMBILICAL CORD-DERIVED MESENCHYMAL STROMAL CELL PRODUCT IN YOUNG CHILDREN WITH AUTISM SPECTRUM DISORDER

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04294290
• Other study ID #: Pro00104460
• Status: Completed
• Phase: Phase 1
• Start date: February 24, 2021
• Est. completion date: August 17, 2022

Study information

• Verified date: January 2023
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: August 17, 2022
• Est. primary completion date: August 17, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Months to 48 Months

Eligibility

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.

Related Conditions & MeSH terms

• Autism Spectrum Disorder
• Autistic Disorder
• Child Development Disorders, Pervasive
• Disease

Intervention

Biological:
• hCT-MSC infusion
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).

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	The Marcus Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of hCT-MSC infusion as measured by incidence of infusion reactions		1 year
Primary	Safety of hCT-MSC infusion as measured by severity of infusion reactions	CTCAE is used to measure severity	1 year
Primary	Safety of hCT-MSC infusion as measured by incidence of product-related infections		1 year
Primary	Safety of hCT-MSC infusion as measured by severity of product-related infections	CTCAE is used to measure severity	1 year
Primary	Safety of hCT-MSC infusion as measured by evidence of alloimmunization via anit-HLA antibodies		1 year
Primary	Safety of hCT-MSC infusion as measured by incidence of graft vs. host disease		1 year
Primary	Safety of hCT-MSC infusion as measured by severity of graft vs. host disease	CTCAE is used to measure severity	1 year
Primary	Safety of hCT-MSC infusion as measured by incidence of unexpected adverse events		1 year
Primary	Safety of hCT-MSC infusion as measured by severity of unexpected adverse events	CTCAE is used to measure severity	1 year
Primary	Change in PDD Behavior Inventory Autism Composite Score (PDDBI)		Baseline, 6 months
Primary	Change in mean of the Socialization Subscale and Communication Subscale standard scores on the Vineland Adaptive Behavior Scales (VABS-3)		baseline, 6 months
Primary	Change in Clinical Global Impression Scale (CGI)		baseline, 6 months
Primary	Change in Communicative Development Inventories (CDI-2)		baseline, 6 months
Primary	Change in attention abilities as assess via eye-tracking		baseline, 6 months
Primary	Change in brain activity as measured by EEG		baseline, 6 months