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A Study of UCB and MSCs in Children With CP: ACCeNT-CP (ACCeNT-CP)

Primary Purpose

Cerebral Palsy

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Infusion of allogeneic umbilical cord blood
Infusion of MSCs
Sponsored by
Joanne Kurtzberg, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cerebral Palsy focused on measuring CP, Cerebral Palsy, Stem Cell, Cord Blood, MSCs

Eligibility Criteria

24 Months - 60 Months (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age ≥24 months and ≤60 months adjusted age at the time of enrollment.
  2. Diagnosis: Unilateral or bilateral hypertonic cerebral palsy secondary to in utero or perinatal stroke/hemorrhage, hypoxic ischemic encephalopathy (including, but not limited to, birth asphyxia), and/or periventricular leukomalacia.
  3. Performance status: Gross Motor Function Classification Score levels I - IV
  4. Review of brain imaging (obtained as standard of care prior to study entry) does not suggest a genetic condition or brain malformation.
  5. Legal authorized representative consent.

Exclusion Criteria:

  1. Available qualified autologous cord blood unit.
  2. Hypotonic or ataxic cerebral palsy without spasticity.
  3. Autism and autistic spectrum disorders.
  4. Hypsarrhythmia.
  5. Legally blind
  6. Intractable seizures causing epileptic encephalopathy.
  7. Evidence of a progressive neurologic disease.
  8. Has an active, uncontrolled systemic infection or documentation of HIV+ status.
  9. Known genetic disease or phenotypic evidence of a genetic disease on physical exam.
  10. Concurrent genetic or acquired disease or comorbidity(ies) that could require a future allogeneic stem cell transplant.
  11. Requires ventilatory support, including home ventilator, CPAP, BiPAP, or supplemental oxygen.
  12. Impaired renal or liver function as determined by serum creatinine >1.5mg/dL and/or total bilirubin >1.3mg/dL except in patients with known Gilbert's disease.
  13. Possible immunosuppression, defined as WBC <3,000 cells/mL or absolute lymphocyte count (ALC) <1500 with abnormal T-cell subsets.
  14. Patient's medical condition does not permit safe travel.
  15. Previously received any form of cellular therapy.

Sites / Locations

  • Duke University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Allogeneic Umbilical Cord Blood

Cord Tissue Mesenchymal Stromal Cells

Natural History

Arm Description

Subjects will receive a single intravenous infusion of a maximum of 10x107/kg allogeneic umbilical cord blood (CB) cells

Subjects will receive three intravenous infusions of 2x106/kg human umbilical cord tissue cells (hCT-MSC), manufactured from allogeneic umbilical cord donors

Subjects will not receive any study product infusion until after the 12 month assessment. At the 12 month visit, they will receive an infusion of allogeneic umbilical cord blood cells so that all study participants will receive some type of cellular therapy.

Outcomes

Primary Outcome Measures

Change in Gross Motor Function Measure (GMFM-66) in Excess of Expected Change
GMFM-66 is used to evaluate gross motor function in children with cerebral palsy and is scored using a propriety software program called the Gross Motor Ability Estimator that produces an interval level continuous score ranging from 0 to 100. Higher scores indicate better motor function. The primary endpoint in this study was computed from the GMFM-66 score in three steps: 1) The "observed" change in motor function from Baseline to Month 12 was calculated (positive values indicate improvement, negative values indicate reduction, and zero indicates no change) for each participant; and 2) The expected change in motor function was determined for each participant based on published growth curves; and 3) The expected change in GMFM-66 was subtracted from the observed change to yield the final primary outcome. Positive values indicate a greater change than would be expected, zero indicates change as expected, and negative values indicate a smaller amount of change than would be expected.

Secondary Outcome Measures

Number of Adverse Events
The secondary endpoint of this study is the number of adverse events occurring over a 12-month period post-treatment with hCT-MSC or AlloCB.

Full Information

First Posted
March 15, 2018
Last Updated
August 17, 2021
Sponsor
Joanne Kurtzberg, MD
Collaborators
The Marcus Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT03473301
Brief Title
A Study of UCB and MSCs in Children With CP: ACCeNT-CP
Acronym
ACCeNT-CP
Official Title
A Phase I/II Study of Allogeneic Umbilical Cord Blood and Umbilical Cord Tissue-Derived Mesenchymal Stromal Cell Infusions in Children With Cerebral Palsy
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
April 10, 2018 (Actual)
Primary Completion Date
February 26, 2020 (Actual)
Study Completion Date
May 31, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Joanne Kurtzberg, MD
Collaborators
The Marcus Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The main purpose of this study is to estimate change in motor function 12 months after treatment with a single dose of allogeneic umbilical cord blood (AlloCB) or repeated doses of umbilical cord tissue-derived mesenchymal stromal cells (hCT-MSC) in children with cerebral palsy. In addition, this study will contribute much needed data to the clinical trials community on the natural history of the motor function in CP over short-term (less than 1 year) time periods relevant to the conduct of clinical trials and assess the safety of AlloCB and hCT-MSC infusion in children with cerebral palsy.
Detailed Description
This study is a phase I/II, prospective, randomized, open-label trial designed to determine the effect size of change in GMFM-66 score in subjects treated with hCT-MSC or allogeneic CB and assess the safety of repeated doses of hCT-MSC in children with cerebral palsy. Children ages 2-5 years with cerebral palsy due to hypoxic ischemic encephalopathy, stroke, or periventricular leukomalacia may be eligible to participate. All participants will ultimately be treated with an allogeneic cell product at some point during the study. Participants will be randomized to one of three arms: (1) the "AlloCB" arm will receive one allogeneic CB infusion at the baseline visit; (2) the "MSC" arm will receive three hCT-MSC infusions, one each at baseline, three months, and six months; (3) the "natural history" arm will not receive an infusion at baseline but will receive an allogeneic CB infusion at 12 months. Motor outcome measures will be assessed at baseline, six-months, and one-year time points. Safety will be evaluated at each infusion visit and remotely for an additional 12 months after the final visit. Duration of study participation will be 24 months from the time of baseline visit. Randomization to treatment arms will be stratified by GMFCS level at study entry and etiology of CP (Stroke vs. Other).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cerebral Palsy
Keywords
CP, Cerebral Palsy, Stem Cell, Cord Blood, MSCs

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Masking Description
Every attempt will be made to blind the outcomes assessor.
Allocation
Randomized
Enrollment
91 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Allogeneic Umbilical Cord Blood
Arm Type
Experimental
Arm Description
Subjects will receive a single intravenous infusion of a maximum of 10x107/kg allogeneic umbilical cord blood (CB) cells
Arm Title
Cord Tissue Mesenchymal Stromal Cells
Arm Type
Experimental
Arm Description
Subjects will receive three intravenous infusions of 2x106/kg human umbilical cord tissue cells (hCT-MSC), manufactured from allogeneic umbilical cord donors
Arm Title
Natural History
Arm Type
Active Comparator
Arm Description
Subjects will not receive any study product infusion until after the 12 month assessment. At the 12 month visit, they will receive an infusion of allogeneic umbilical cord blood cells so that all study participants will receive some type of cellular therapy.
Intervention Type
Biological
Intervention Name(s)
Infusion of allogeneic umbilical cord blood
Intervention Description
Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.
Intervention Type
Biological
Intervention Name(s)
Infusion of MSCs
Intervention Description
Subjects will receive 3 infusions of MSCs (baseline, 3 months and 6 months).
Primary Outcome Measure Information:
Title
Change in Gross Motor Function Measure (GMFM-66) in Excess of Expected Change
Description
GMFM-66 is used to evaluate gross motor function in children with cerebral palsy and is scored using a propriety software program called the Gross Motor Ability Estimator that produces an interval level continuous score ranging from 0 to 100. Higher scores indicate better motor function. The primary endpoint in this study was computed from the GMFM-66 score in three steps: 1) The "observed" change in motor function from Baseline to Month 12 was calculated (positive values indicate improvement, negative values indicate reduction, and zero indicates no change) for each participant; and 2) The expected change in motor function was determined for each participant based on published growth curves; and 3) The expected change in GMFM-66 was subtracted from the observed change to yield the final primary outcome. Positive values indicate a greater change than would be expected, zero indicates change as expected, and negative values indicate a smaller amount of change than would be expected.
Time Frame
Baseline to 12 months
Secondary Outcome Measure Information:
Title
Number of Adverse Events
Description
The secondary endpoint of this study is the number of adverse events occurring over a 12-month period post-treatment with hCT-MSC or AlloCB.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
24 Months
Maximum Age & Unit of Time
60 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥24 months and ≤60 months adjusted age at the time of enrollment. Diagnosis: Unilateral or bilateral hypertonic cerebral palsy secondary to in utero or perinatal stroke/hemorrhage, hypoxic ischemic encephalopathy (including, but not limited to, birth asphyxia), and/or periventricular leukomalacia. Performance status: Gross Motor Function Classification Score levels I - IV Review of brain imaging (obtained as standard of care prior to study entry) does not suggest a genetic condition or brain malformation. Legal authorized representative consent. Exclusion Criteria: Available qualified autologous cord blood unit. Hypotonic or ataxic cerebral palsy without spasticity. Autism and autistic spectrum disorders. Hypsarrhythmia. Legally blind Intractable seizures causing epileptic encephalopathy. Evidence of a progressive neurologic disease. Has an active, uncontrolled systemic infection or documentation of HIV+ status. Known genetic disease or phenotypic evidence of a genetic disease on physical exam. Concurrent genetic or acquired disease or comorbidity(ies) that could require a future allogeneic stem cell transplant. Requires ventilatory support, including home ventilator, CPAP, BiPAP, or supplemental oxygen. Impaired renal or liver function as determined by serum creatinine >1.5mg/dL and/or total bilirubin >1.3mg/dL except in patients with known Gilbert's disease. Possible immunosuppression, defined as WBC <3,000 cells/mL or absolute lymphocyte count (ALC) <1500 with abnormal T-cell subsets. Patient's medical condition does not permit safe travel. Previously received any form of cellular therapy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joanne Kurtzberg, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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A Study of UCB and MSCs in Children With CP: ACCeNT-CP

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