A PHASE I STUDY OF hCT-MSC, AN UMBILICAL CORD-DERIVED MESENCHYMAL STROMAL CELL PRODUCT, IN ADULTS WITH AUTISM SPECTRUM DISORDER

PRO00104691

The purpose of the study is to determine the safety and tolerability of a single intravenous dose of Human Umbilical Cord Tissue Derived Mesenchymal Stromal Cells (hCT-MSC) in adults with autism spectrum disorder (ASD). hCT-MSC is a cell product isolated from umbilical cord tissue. The cells from the cord tissue are processed and expanded in the laboratory and then infused intravenously in a single dose per participant. Participants will be ages 18-35 years, with ASD and a full-scale IQ \>70 without an identified genetic cause of autism. Participants will have an in-person baseline visit and remote follow up visits at 6 and 12 months. In addition to the primary endpoints evaluating safety, the study will evaluate changes in social communications skills after hCT-MSC administration.

2022-01-24

2024-06-01

2024-06-01

Active (not recruiting)

Early phase I

11

Inclusion Criteria: 1. Age ≥18 to \< 35 years (34 years, 364 days) at the time of consent 2. Confirmed pre-existing diagnosis of ASD in the individual's educational and/or medical record 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, with no intention of changing or beginning new psychiatric medications or behavioral treatments during the duration of the study. 5. Normal absolute lymphocyte count (≥1200/uL for African American participants and ≥1500/uL for all other participants) 6. General Ability Index of ≥70, confirmed through cognitive testing completed by study personnel to establish eligibility 7. Participant and Parent are English speaking 8. Able to travel to Duke University for baseline visit. 9. Participant has a parent who spends four or more hours a week with the participant, who is able and willing to participate in study visits and interim surveys and interviews 10. Informed consent of the participant and parent (participants must have legal authority regarding their own medical care and a parent or legally authorized representative may not consent on their behalf) Exclusion Criteria 1. General: 1. Review of medical records indicates ASD diagnosis and IQ \> 70 unlikely. 2. Known or suspected diagnosis of any of the following coexisting psychiatric conditions: bipolar disorder, schizophrenia, Tourette syndrome, and/or any co-occurring psychiatric disorder that the investigator believes would interfere with accurate completion of study instruments and/or current (within the past year) evidence of suicidality as assessed by an interview with participant and/or parent which includes the Columbia Suicide Severity Rating Scale, and a review of responses on the Behavioral and Symptom Identification Scale (BASIS-24). 3. Screening data or in-person evaluations suggest that participant would not be able to comply with the requirements of the study procedures as assessed by the study team 4. Parent and/or participant is unwilling or unable to commit to participation in all study-related assessments, including protocol follow up 5. Sibling is enrolled in this (Duke AIMs) study 2. Genetic: 1. Records indicate that the participant 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 participant 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 participants 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. 13. Current pregnancy and unwillingness to use adequate birth control for 3 months after the final study product infusion. 5. Current/Prior Therapy: a. Availability of a banked, qualified autologous cord blood unit or parent 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 \>5 days within 4 weeks, prior to enrollment. Topical and inhaled steroids are permitted.

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2023-12-14