IMPACT: hCT-MSC in Children With Autism Spectrum Disorder

Sponsor

Joanne Kurtzberg, MD (Other)

Overall Status

Recruiting

CT.gov ID

NCT04089579

Collaborator

The Marcus Foundation (Other)

164

Enrollment

Location

Arms

33.6

Anticipated Duration (Months)

4.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Autism Autism Spectrum Disorder	Biological: Cord Tissue Mesenchymal Stromal Cells Other: Placebo Infusion	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

164 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

This study is a phase II, prospective, randomized, blinded, cross over, clinical trial designed to assess the efficacy of intravenous dosing of hCT-MSC for improving social communication abilities in young children with ASD. All participants will ultimately be treated with hCT-MSC. Participants randomized to arm A will each receive a single intravenous dose of 6x106 hCT-MSC per kilogram at baseline, followed by a placebo infusion at six months. Participants randomized to arm B will each receive a placebo infusion at baseline, followed by an intravenous dose of 6x106 hCT-MSC per kilogram at six months.This study is a phase II, prospective, randomized, blinded, cross over, clinical trial designed to assess the efficacy of intravenous dosing of hCT-MSC for improving social communication abilities in young children with ASD. All participants will ultimately be treated with hCT-MSC. Participants randomized to arm A will each receive a single intravenous dose of 6x106 hCT-MSC per kilogram at baseline, followed by a placebo infusion at six months. Participants randomized to arm B will each receive a placebo infusion at baseline, followed by an intravenous dose of 6x106 hCT-MSC per kilogram at six months.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Blinded infusion

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 12, 2020

Anticipated Primary Completion Date :

Feb 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change on the Socialization and Communication Subscale Standard Scores on the Vineland Behavior Scales [Baseline, 6 months]
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.

Secondary Outcome Measures

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

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

4 Years to 11 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Age ≥ 4 years to < 12 years (11 years, 364 days) at the time of consent
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)
Fragile X testing performed and negative; CMA and/or whole exome sequencing performed and results not linked to autism diagnosis
Stable on current psychiatric medication regimen (dose and dosing schedule) for at least 2 months prior to infusion of study product
Normal absolute lymphocyte count (≥1200/uL for African American participants and ≥1500/uL for all other participants)
GAI ≥ 65 via cognitive testing by study personnel
Participant and parent/guardian are English speaking
Able to travel to Duke University two times (baseline, six months), and parent/guardian is able to participate in interim surveys and interviews
Parental/guardian consent from at least one parent/guardian

Exclusion Criteria

General:
Review of medical records and/or screening assessments indicates ASD diagnosis and/or GAI > 65 not confident
Known diagnosis of any of the following coexisting psychiatric conditions: depression, bipolar disorder, schizophrenia, obsessive compulsive disorder associated with bipolar disorder, Tourette syndrome
Screening data suggests that participant would not be able to comply with the requirements of the study procedures as assessed by the study team
Family is unwilling or unable to commit to participation in all study-related assessments, including protocol follow up
Sibling is enrolled in this (Duke IMPACT) study
Genetic:
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
Known pathogenic mutation or copy number variation (CNV) associated with ASD (e.g., 16p11.2, 15q13.2, 2q13.3)
Infectious:
Known active CNS infection
Evidence of uncontrolled infection based on records or clinical assessment
Known HIV positivity
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.
Medical:
Known metabolic disorder
Known mitochondrial dysfunction
History of unstable epilepsy or uncontrolled seizure disorder, infantile spasms, Lennox Gastaut syndrome, Dravet syndrome, or other similar chronic seizure disorder
Active malignancy or prior malignancy that was treated with chemotherapy
History of a primary immunodeficiency disorder
History of autoimmune cytopenias (i.e., ITP, AIHA)
Coexisting medical condition that would place the child at increased risk for complications of study procedures
Concurrent genetic or acquired disease or comorbidity(ies) that could require a future stem cell transplant
Significant sensory (e.g., blindness, deafness, uncorrected hearing impairment) or motor (e.g., cerebral palsy) impairment
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
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.
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.
Current/Prior Therapy:

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.