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

NCT03473301 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: Pro00089362
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 1

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.

Conditions

Cerebral Palsy

Keywords

CP; Cerebral Palsy; Stem Cell; Cord Blood; MSCs

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to 12 months

Secondary Outcomes (1)

• Number of Adverse Events

  12 months

Study Arms (3)

Allogeneic Umbilical Cord Blood

EXPERIMENTAL

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

Biological: Infusion of allogeneic umbilical cord blood

Cord Tissue Mesenchymal Stromal Cells

EXPERIMENTAL

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

Biological: Infusion of MSCs

Natural History

ACTIVE COMPARATOR

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.

Biological: Infusion of allogeneic umbilical cord blood

Interventions

Infusion of allogeneic umbilical cord blood BIOLOGICAL

Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.

Allogeneic Umbilical Cord Blood; Natural History

Infusion of MSCs BIOLOGICAL

Subjects will receive 3 infusions of MSCs (baseline, 3 months and 6 months).

Cord Tissue Mesenchymal Stromal Cells

Eligibility Criteria

• Age: 24 Months - 60 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Joanne Kurtzberg, MD: lead
• The Marcus Foundation: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Related Publications (2)

• Liu J, Poehlein E, Chow SC. Statistical Evaluation of Responder Analysis in Stem Cell Clinical Trials. Ther Innov Regul Sci. 2023 Nov;57(6):1238-1247. doi: 10.1007/s43441-023-00556-8. Epub 2023 Aug 9.

  PMID: 37555886 DERIVED

• Sun JM, Case LE, McLaughlin C, Burgess A, Skergan N, Crane S, Jasien JM, Mikati MA, Troy J, Kurtzberg J. Motor function and safety after allogeneic cord blood and cord tissue-derived mesenchymal stromal cells in cerebral palsy: An open-label, randomized trial. Dev Med Child Neurol. 2022 Dec;64(12):1477-1486. doi: 10.1111/dmcn.15325. Epub 2022 Jul 10.

  PMID: 35811372 DERIVED

MeSH Terms

Conditions

Cerebral Palsy

Condition Hierarchy (Ancestors)

Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Jesse D. Troy, PhD, MPH
• Organization: Duke University

cordbloodtherapyinfo@dm.duke.edu

919-668-1102

Study Officials

• Joanne Kurtzberg, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Every attempt will be made to blind the outcomes assessor.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: March 15, 2018
• First Posted: March 22, 2018
• Study Start: April 10, 2018
• Primary Completion: February 26, 2020
• Study Completion: May 31, 2021
• Last Updated: August 19, 2021
• Results First Posted: February 17, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)