hCT-MSCs for Children With Autism Spectrum Disorder (ASD)

This study is a phase I, prospective, open-label trial designed to assess the safety of one,
two, and three intravenous doses of hCT-MSC in young children with ASD. Children ages two to
11 years with ASD will be eligible to participate. All participants will receive intravenous
infusion(s) of CTCs. The first cohort of three patients will receive a single dose. If there
are no safety concerns, the second cohort of three patients will receive two doses, given two
months apart. The third cohort will consist of six patients, each of whom will receive three
hCT-MSC infusions with a two-month interval between doses. All participants will have an
initial clinical evaluation to verify the diagnosis of ASD and confirm protocol eligibility.
The main endpoint is safety, for which acute infusion reactions and incidence of infections
will be assessed. ASD-specific outcome measures, described below, will be assessed at
baseline and six months from baseline and results will be described.

Inclusion Criteria:

1. Age ≥ 2 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 with a moderate severity level of ASD as reflected by SRS score ≥ 66 and
CGI-S severity score of ≥ 4.

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 (≥1500/uL)

6. Participant and parent/guardian are English speaking

7. Able to travel to Duke University up to four times (baseline, every two months for
subsequent infusions, and 6 months after initial infusion), 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. 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 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 defect
definitively known to be associated with ASD

2. Evaluation by geneticist (performed locally as standard of care or remotely by
the study geneticist via review of available data - minimally medical records,
photos, Fragile X and CMA testing) indicates a genetic cause for ASD.

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 abnormal thyroid function (patients with treated hypothyroidism with a
normal TSH may be included)

3. Known mitochondrial dysfunction

4. History of unstable epilepsy or uncontrolled seizure disorder, infantile spasms,
Lennox Gastaut syndrome, Dravet syndrome, or other similar chronic seizure
disorder

5. Active malignancy or prior malignancy that was treated with chemotherapy

6. History of a primary immunodeficiency disorder

7. History of autoimmune cytopenias (i.e., ITP, AIHA)

8. Coexisting medical condition that would place the child at increased risk for
complications of study procedures

9. Concurrent genetic or acquired disease or comorbidity(ies) that could require a
future stem cell transplant

10. Significant sensory (e.g., blindness, deafness, uncorrected hearing impairment)
or motor (e.g., cerebral palsy) impairment

11. 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

12. Significant hematologic abnormalities defined as: Hemoglobin <10.0 g/dL, WBC <
3,000 cells/mL, ALC <1000/uL, Platelets <150 x 10e9/uL

13. 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 dysmporphic features
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.