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

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ClinicalTrials.gov Identifier: NCT03473301

Recruitment Status : Completed

First Posted : March 22, 2018

Results First Posted : February 17, 2021

Last Update Posted : August 19, 2021

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

The Marcus Foundation

Information provided by (Responsible Party):

Joanne Kurtzberg, MD, Duke University

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
Condition	Cerebral Palsy
Interventions	Biological: Infusion of allogeneic umbilical cord blood Biological: Infusion of MSCs
Enrollment	91

Participant Flow

Recruitment Details	First participant randomized on April 10, 2018. Last participant randomized May 30, 2019. Single center study.
Pre-assignment Details


Arm/Group Title	Allogeneic Umbilical Cord Blood (AlloCB)	Cord Tissue Mesenchymal Stromal Cells (MSC)	Natural History, Then AlloCB
Arm/Group Description	Subjects will receive a single intr...	Subjects will receive three intrave...	Subjects will not receive any study...
Arm/Group Description	Subjects will receive a single intravenous infusion of a maximum of 10x107/kg allogeneic umbilical cord blood (CB) cells Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.	Subjects will receive three intravenous infusions of 2x106/kg human umbilical cord tissue cells (hCT-MSC), manufactured from allogeneic umbilical cord donors Infusion of MSCs: Subjects will receive 3 infusions of MSCs (baseline, 3 months and 6 months).	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. Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.
Period Title: Overall Study
Started	31	29	31
Completed	20	23	25
Not Completed	11	6	6
Reason Not Completed
Protocol Violation	4	0	0
Withdrawal by Subject	0	1	0
Missed study visit due to pandemic restrictions	7	5	6

Baseline Characteristics

Arm/Group Title		Allogeneic Umbilical Cord Blood (AlloCB)	Cord Tissue Mesenchymal Stromal Cells (MSC)	Natural History, Then AlloCB	Total
Arm/Group Description		Subjects will receive a single intr...	Subjects will receive three intrave...	Subjects will not receive any study...	Total of all reporting groups
Arm/Group Description		Subjects will receive a single intravenous infusion of a maximum of 10x107/kg allogeneic umbilical cord blood (CB) cells Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.	Subjects will receive three intravenous infusions of 2x106/kg human umbilical cord tissue cells (hCT-MSC), manufactured from allogeneic umbilical cord donors Infusion of MSCs: Subjects will receive 3 infusions of MSCs (baseline, 3 months and 6 months).	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. Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.	Total of all reporting groups
Overall Number of Baseline Participants		31	29	31	91
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	31 participants	29 participants	31 participants	91 participants
		3.47 (0.96)	3.53 (0.88)	3.55 (0.84)	3.52 (0.89)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	31 participants	29 participants	31 participants	91 participants
	Female	16 51.6%	9 31.0%	14 45.2%	39 42.9%
	Male	15 48.4%	20 69.0%	17 54.8%	52 57.1%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	31 participants	29 participants	31 participants	91 participants
	Hispanic or Latino	4 12.9%	2 6.9%	6 19.4%	12 13.2%
	Not Hispanic or Latino	27 87.1%	27 93.1%	25 80.6%	79 86.8%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	31 participants	29 participants	31 participants	91 participants
Asian		0 0.0%	3 10.3%	3 9.7%	6 6.6%
British Indian		0 0.0%	0 0.0%	1 3.2%	1 1.1%
Italian		0 0.0%	0 0.0%	1 3.2%	1 1.1%
White		30 96.8%	25 86.2%	24 77.4%	79 86.8%
More than one race		1 3.2%	1 3.4%	2 6.5%	4 4.4%
Region of Enrollment Measure Type: Count of Participants Unit of measure: Participants
United States	Number Analyzed	31 participants	29 participants	31 participants	91 participants
United States		31 100.0%	29 100.0%	31 100.0%	91 100.0%

Outcome Measures

1.Primary Outcome


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 cere...
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

Outcome Measure Data

Analysis Population Description

Efficacy data not collected on Natural History participants after receiving allogeneic umbilical cord blood. Participants who did not complete the Month 12 visit are excluded.


Arm/Group Title	Allogeneic Umbilical Cord Blood (AlloCB)	Cord Tissue Mesenchymal Stromal Cells (MSC)	Natural History	AlloCB After Natural History
Arm/Group Description:	Subjects will receive a single intr...	Subjects will receive three intrave...	Subjects will not receive any study...	Subjects will not receive any study...
Arm/Group Description:	Subjects will receive a single intravenous infusion of a maximum of 10x107/kg allogeneic umbilical cord blood (CB) cells Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.	Subjects will receive three intravenous infusions of 2x106/kg human umbilical cord tissue cells (hCT-MSC), manufactured from allogeneic umbilical cord donors Infusion of MSCs: Subjects will receive 3 infusions of MSCs (baseline, 3 months and 6 months).	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. Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.	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. Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.
Overall Number of Participants Analyzed	20	23	25	0
Mean (95% Confidence Interval) Unit of Measure: score on a scale
	5.83 (3.44 to 8.21)	4.27 (2.17 to 6.36)	3.15 (1.31 to 4.99)

2.Secondary Outcome


Title	Number of Adverse Events
Description	The secondary endpoint of this study is the number of adverse events o...
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

Outcome Measure Data

Analysis Population Description

Four participants randomized to the Natural History arm did not receive an infusion of AlloCB at Month12.


Arm/Group Title	Allogeneic Umbilical Cord Blood (AlloCB)	Cord Tissue Mesenchymal Stromal Cells (MSC)	Natural History	AlloCB After Natural History
Arm/Group Description:	Subjects will receive a single intr...	Subjects will receive three intrave...	Subjects will not receive any study...	Subjects will not receive any study...
Arm/Group Description:	Subjects will receive a single intravenous infusion of a maximum of 10x107/kg allogeneic umbilical cord blood (CB) cells Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.	Subjects will receive three intravenous infusions of 2x106/kg human umbilical cord tissue cells (hCT-MSC), manufactured from allogeneic umbilical cord donors Infusion of MSCs: Subjects will receive 3 infusions of MSCs (baseline, 3 months and 6 months).	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. Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.	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. Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.
Overall Number of Participants Analyzed	31	29	31	27
Measure Type: Number Unit of Measure: adverse events
	30	48	16	9

Adverse Events

Time Frame	12 months
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Allogeneic Umbilical Cord Blood (AlloCB)	Cord Tissue Mesenchymal Stromal Cells (MSC)	Natural History	AlloCB After Natural History
Arm/Group Description	Subjects will receive a single intr...	Subjects will receive three intrave...	Subjects will not receive any study...	Subjects will not receive any study...
Arm/Group Description	Subjects will receive a single intravenous infusion of a maximum of 10x107/kg allogeneic umbilical cord blood (CB) cells Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.	Subjects will receive three intravenous infusions of 2x106/kg human umbilical cord tissue cells (hCT-MSC), manufactured from allogeneic umbilical cord donors Infusion of MSCs: Subjects will receive 3 infusions of MSCs (baseline, 3 months and 6 months).	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. Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.	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. Infusion of allogeneic umbilical cord blood: Subjects will receive a single infusion of allogeneic umbilical cord blood at the baseline visit.
All-Cause Mortality
	Allogeneic Umbilical Cord Blood (AlloCB)	Cord Tissue Mesenchymal Stromal Cells (MSC)	Natural History	AlloCB After Natural History
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/31 (0.00%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Serious Adverse Events Serious Adverse Events
	Allogeneic Umbilical Cord Blood (AlloCB)	Cord Tissue Mesenchymal Stromal Cells (MSC)	Natural History	AlloCB After Natural History
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	9/31 (29.03%)	3/29 (10.34%)	9/31 (29.03%)	3/27 (11.11%)
Gastrointestinal disorders
Gastritis ^† 1	1/31 (3.23%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Infections and infestations
Bronchitis viral ^† 1	1/31 (3.23%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Respiratory syncytial virus infection ^† 1	1/31 (3.23%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Respiratory tract infection viral ^† 1	0/31 (0.00%)	0/29 (0.00%)	1/31 (3.23%)	0/27 (0.00%)
Rhinovirus infection ^† 1	1/31 (3.23%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Metabolism and nutrition disorders
Dehydration ^† 1	1/31 (3.23%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Nervous system disorders
Seizure ^† 1	2/31 (6.45%)	0/29 (0.00%)	5/31 (16.13%)	1/27 (3.70%)
Psychiatric disorders
Sleep disorder ^† 1	0/31 (0.00%)	1/29 (3.45%)	0/31 (0.00%)	0/27 (0.00%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure ^† 1	0/31 (0.00%)	0/29 (0.00%)	1/31 (3.23%)	0/27 (0.00%)
Surgical and medical procedures
Hospitalisation ^† 1	0/31 (0.00%)	2/29 (6.90%)	2/31 (6.45%)	2/27 (7.41%)
Surgery ^† 1	3/31 (9.68%)	0/29 (0.00%)	1/31 (3.23%)	0/27 (0.00%)
Tonsillectomy ^† 1	0/31 (0.00%)	0/29 (0.00%)	1/31 (3.23%)	0/27 (0.00%)
1 Term from vocabulary, MedDRA † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Allogeneic Umbilical Cord Blood (AlloCB)	Cord Tissue Mesenchymal Stromal Cells (MSC)	Natural History	AlloCB After Natural History
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	18/31 (58.06%)	22/29 (75.86%)	12/31 (38.71%)	6/27 (22.22%)
Blood and lymphatic system disorders
Thrombocytopenia ^† 1	0/31 (0.00%)	0/29 (0.00%)	1/31 (3.23%)	0/27 (0.00%)
Anaemia ^† 1	0/31 (0.00%)	1/29 (3.45%)	0/31 (0.00%)	0/27 (0.00%)
Cardiac disorders
Bradycardia ^† 1	0/31 (0.00%)	0/29 (0.00%)	1/31 (3.23%)	0/27 (0.00%)
Ear and labyrinth disorders
Hypoacusis ^† 1	1/31 (3.23%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Gastrointestinal disorders
Gastroesophageal reflux disease ^† 1	0/31 (0.00%)	0/29 (0.00%)	1/31 (3.23%)	0/27 (0.00%)
Cyclic vomiting syndrome ^† 1	0/31 (0.00%)	0/29 (0.00%)	0/31 (0.00%)	1/27 (3.70%)
Toothache ^† 1	0/31 (0.00%)	0/29 (0.00%)	0/31 (0.00%)	1/27 (3.70%)
Constipation ^† 1	1/31 (3.23%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Diarrhoea ^† 1	1/31 (3.23%)	1/29 (3.45%)	0/31 (0.00%)	0/27 (0.00%)
Vomiting ^† 1	1/31 (3.23%)	2/29 (6.90%)	0/31 (0.00%)	0/27 (0.00%)
General disorders
Pyrexia ^† 1	2/31 (6.45%)	3/29 (10.34%)	2/31 (6.45%)	1/27 (3.70%)
Fatigue ^† 1	1/31 (3.23%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Influenza like illness ^† 1	0/31 (0.00%)	1/29 (3.45%)	0/31 (0.00%)	0/27 (0.00%)
Infusion site rash ^† 1	0/31 (0.00%)	1/29 (3.45%)	0/31 (0.00%)	0/27 (0.00%)
Injection site reaction ^† 1	0/31 (0.00%)	1/29 (3.45%)	0/31 (0.00%)	0/27 (0.00%)
Immune system disorders
Anaphylactic reaction ^† 1	1/31 (3.23%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Drug hypersensitivity ^† 1	0/31 (0.00%)	1/29 (3.45%)	0/31 (0.00%)	0/27 (0.00%)
Infections and infestations
Bronchitis ^† 1	0/31 (0.00%)	0/29 (0.00%)	1/31 (3.23%)	0/27 (0.00%)
Enterocolitis infectious ^† 1	0/31 (0.00%)	0/29 (0.00%)	1/31 (3.23%)	0/27 (0.00%)
Otitis media ^† 1	2/31 (6.45%)	2/29 (6.90%)	1/31 (3.23%)	0/27 (0.00%)
Hand-foot-and-mouth disease ^† 1	2/31 (6.45%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Influenza ^† 1	1/31 (3.23%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Pneumonia ^† 1	1/31 (3.23%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Upper respiratory tract infection ^† 1	1/31 (3.23%)	8/29 (27.59%)	0/31 (0.00%)	0/27 (0.00%)
Tonsillitis ^† 1	0/31 (0.00%)	1/29 (3.45%)	0/31 (0.00%)	0/27 (0.00%)
Varicella ^† 1	0/31 (0.00%)	1/29 (3.45%)	0/31 (0.00%)	0/27 (0.00%)
Injury, poisoning and procedural complications
Fall ^† 1	2/31 (6.45%)	1/29 (3.45%)	1/31 (3.23%)	0/27 (0.00%)
Fracture ^† 1	0/31 (0.00%)	0/29 (0.00%)	1/31 (3.23%)	0/27 (0.00%)
Infusion related reaction ^† 1	1/31 (3.23%)	4/29 (13.79%)	0/31 (0.00%)	2/27 (7.41%)
Arthropod bite ^† 1	1/31 (3.23%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Tooth avulsion ^† 1	1/31 (3.23%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Investigations
Laboratory test abnormal ^† 1	2/31 (6.45%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Metabolism and nutrition disorders
Dehydration ^† 1	1/31 (3.23%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Nervous system disorders
Nervous system disorder ^† 1	0/31 (0.00%)	0/29 (0.00%)	1/31 (3.23%)	0/27 (0.00%)
Seizure ^† 1	0/31 (0.00%)	6/29 (20.69%)	2/31 (6.45%)	0/27 (0.00%)
Headache ^† 1	0/31 (0.00%)	2/29 (6.90%)	0/31 (0.00%)	1/27 (3.70%)
Facial paresis ^† 1	1/31 (3.23%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Partial seizures ^† 1	1/31 (3.23%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Disturbance in attention ^† 1	0/31 (0.00%)	1/29 (3.45%)	0/31 (0.00%)	0/27 (0.00%)
Psychiatric disorders
Insomnia ^† 1	0/31 (0.00%)	1/29 (3.45%)	0/31 (0.00%)	0/27 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	0/31 (0.00%)	0/29 (0.00%)	0/31 (0.00%)	1/27 (3.70%)
Skin and subcutaneous tissue disorders
Rash ^† 1	0/31 (0.00%)	4/29 (13.79%)	0/31 (0.00%)	1/27 (3.70%)
Henoch-Schonlein purpura ^† 1	0/31 (0.00%)	1/29 (3.45%)	0/31 (0.00%)	0/27 (0.00%)
Rash maculo-papular ^† 1	0/31 (0.00%)	2/29 (6.90%)	0/31 (0.00%)	0/27 (0.00%)
Urticaria ^† 1	0/31 (0.00%)	1/29 (3.45%)	0/31 (0.00%)	0/27 (0.00%)
Surgical and medical procedures
Adenotonsillectomy ^† 1	0/31 (0.00%)	0/29 (0.00%)	1/31 (3.23%)	0/27 (0.00%)
Strabismus correction ^† 1	1/31 (3.23%)	0/29 (0.00%)	2/31 (6.45%)	0/27 (0.00%)
Dental operation ^† 1	1/31 (3.23%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Orchidopexy ^† 1	1/31 (3.23%)	1/29 (3.45%)	0/31 (0.00%)	0/27 (0.00%)
Suture insertion ^† 1	1/31 (3.23%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Tongue tie operation ^† 1	1/31 (3.23%)	0/29 (0.00%)	0/31 (0.00%)	0/27 (0.00%)
Adenoidectomy ^† 1	0/31 (0.00%)	1/29 (3.45%)	0/31 (0.00%)	0/27 (0.00%)
1 Term from vocabulary, MedDRA † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Jesse D. Troy, PhD, MPH
Organization:	Duke University
Phone:	919-668-1102
EMail:	cordbloodtherapyinfo@dm.duke.edu

Layout table for additonal information

Responsible Party:	Joanne Kurtzberg, MD, Duke University
ClinicalTrials.gov Identifier:	NCT03473301
Other Study ID Numbers:	Pro00089362
First Submitted:	March 15, 2018
First Posted:	March 22, 2018
Results First Submitted:	January 27, 2021
Results First Posted:	February 17, 2021
Last Update Posted:	August 19, 2021

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