Dose Escalation Study of AST-OPC1 in Spinal Cord Injury

• Sponsor: Lineage Cell Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02302157
• Collaborator: (none)
• Enrollment: 25
• Locations: 9
• Arm: 1
• Duration (Months): 45
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety of cross sequential escalating doses of AST-OPC1 administered among 5 cohorts at a single time-point between 21 and 42 days post injury, inclusively, to subjects with subacute cervical spinal cord injuries (SCI).

Condition or Disease	Intervention/Treatment	Phase
Cervical Spinal Cord Injury; Spine Injury; Spinal Cord Trauma	Biological: AST-OPC1	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2a Dose Escalation Study of AST-OPC1 in Subjects With Subacute Cervical Spinal Cord Injury
• Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: Dec 1, 2018
• Actual Study Completion Date: Dec 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AST-OPC1 Open label, dose escalation, cross-sequential cohort of subjects who receive an injection or two injections of AST-OPC1 at a single time-point	Biological: AST-OPC1; One injection of 2 million or 10 million AST-OPC1 cells, or 2 injections of 10 million AST-OPC1 cells for a total of 20 million cells; cohort dependent

Outcome Measures

Primary Outcome Measures

1. Number of Adverse Events Within 1 Year (365 Days) That Are Related to AST-OPC1 Injection [One Year]

   Numbers of adverse events within 1 year (365 days) that are related to AST-OPC1 injection

Secondary Outcome Measures

1. Neurological Function as Measured by Upper Extremity Motor Scores and Motor Level on International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) Examinations as Secondary End Point - 365 Days After Injection of AST-OPC1 [One Year]

   The scale is based on the ISNCSCI (International Standards for Neurological Classification of Spinal Cord Injury) that measures the severity of Spinal cord injury. The data was collected per time point during the first year (30,60,90,180,270,365). The 365-days time point was pre-specified as Secondary Outcome Measure. High score means better outcome. Units are "Scores on a scale". The score is divided to motor scale (0-100) and sensor scale (0-224). Motor scale is divided to subscale of upper extremity (0-50) and lower extremity (0-50). Upper and lower extremity are divided to subscale of Right (0-25) + Left (0-25). Each upper & lower extremity is divided to subscale of 5 motor nerve function (0-5). Sensor scale is divided to subscale of light touch (0-112) and pin prick (0-112). light touch and pin prick are divided to subscales of Right (0-56) + Left (0-56). Each right and left light touch and pin prick are divided to subscales of 28 sensor nerve function (0-2)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 69 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Major Inclusion Criteria:

• Sensorimotor complete, traumatic SCI (ASIA Impairment Scale A) for cohorts 1,2,3

• Sensorimotor incomplete, traumatic SCI (ASIA Impairment Scale B) for cohorts 4,5

• Last fully preserved single neurological level (SNL) from C-4 to C-7

• From 18 through 69 years of age at time of injury

• Single spinal cord lesion on a post-stabilization magnetic resonance imaging (MRI) scan, with sufficient visualization of the spinal cord injury epicenter and lesion margins to enable post-injection safety monitoring

• Informed consent for this protocol and the companion long term follow-up protocol must be provided and documented (i.e., signed informed consent forms) no later than 37 days following injury

• Able to participate in an elective surgical procedure to inject AST-OPC1 21-42 days following SCI

Major Exclusion Criteria:

• SCI due to penetrating trauma

• Traumatic anatomical transection or laceration of the spinal cord based on prior surgery or MRI

• Any concomitant injury that interferes with the performance, interpretation or validity of neurological examinations

• Inability to communicate effectively with neurological examiner such that the validity of patient data could be compromised

• Significant organ damage or systemic disease that would create an unacceptable risk for surgery or immunosuppression

• History of any malignancy (except non-melanoma skin cancers)

• Pregnant or nursing women

• Body mass index (BMI) > 35 or weight > 300 lbs.

• Active participation in another experimental procedure/intervention

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univ. of California at San Diego	La Jolla	California	United States	92093
2	Rancho Los Amigos/USC	Los Angeles	California	United States
3	Stanford University/Santa Clara Valley Medical Center	San Jose	California	United States	95128
4	Shepherd Center	Atlanta	Georgia	United States	30309
5	Rush University Medical Center	Chicago	Illinois	United States	60612
6	Indiana University	Indianapolis	Indiana	United States	46202
7	Washington University	Saint Louis	Missouri	United States	63110
8	Thomas Jefferson University/Magee Rehabilitation	Philadelphia	Pennsylvania	United States	19107
9	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Lineage Cell Therapeutics, Inc.

Investigators

• Study Director: Edward D Wirth III, MD, PhD, Asterias Biotherapeutics

Study Documents (Full-Text)

• Study Protocol - Jul 7, 2017
• Statistical Analysis Plan - Oct 3, 2018

More Information

Publications

None provided.

• Responsible Party: Lineage Cell Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02302157
• Other Study ID Numbers: AST-OPC1-01
• First Posted: Nov 26, 2014
• Last Update Posted: Jul 14, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by Lineage Cell Therapeutics, Inc.: Cervical spinal cord injury; AST-OPC1; SCiStar; OPC1; Neural cell; Trauma spinal cord; stemcell transplant; Cervical spine injury; Paralysis; Quadriplegia; Tetraplegia; Spine injury; oligodendrocyte progenitor cell; Subacute spinal cord injury
• Additional relevant MeSH terms: Spinal Cord Injuries; Wounds and Injuries; Spinal Injuries

Study Results

Participant Flow

Arm/Group Title	AST-OPC1, Cohort 1	AST-OPC1, Cohort 2	AST-OPC1, Cohort 3	AST-OPC1, Cohort 4	AST-OPC1, Cohort 5
Arm/Group Description	n=3 subjects Dosage of 2 million cells AIS score A	n=6 subjects Dosage 10 million cells AIS score A	n=6 subjects Dosage of 20 million cells AIS score A	n=6 subjects Dosage of 10 million AIS score B	n=4 subjects Dosage of 20 million cells AIS score B
Period Title: Overall Study
STARTED	3	6	6	6	4
COMPLETED	3	6	6	6	4
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	AST-OPC1, Cohort 1	AST-OPC1, Cohort 2	AST-OPC1, Cohort 3	AST-OPC1, Cohort 4	AST-OPC1, Cohort 5	Total
Arm/Group Description	n=3 Dosage of 2 million cells AIS score A	n=6 Dosage of 10 million cells AIS score A	n=6 Dosage of 20 million cells AIS score A	n=6 Dosage of 10 million cells AIS score B	n=4 Dosage of 20 million cells AIS score B	Total of all reporting groups
Overall Participants	3	6	6	6	4	25
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	3 100%	6 100%	6 100%	6 100%	4 100%	25 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	24.3 (6.1)	24.5 (7.4)	44.7 (14.7)	28.5 (14.1)	34.3 (20.7)	30.8 (14.8)
Sex: Female, Male (Count of Participants)
Female	0 0%	1 16.7%	1 16.7%	0 0%	2 50%	4 16%
Male	3 100%	5 83.3%	5 83.3%	6 100%	2 50%	21 84%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	1 25%	1 4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	1 25%	1 4%
Black or African American	0 0%	1 16.7%	0 0%	0 0%	0 0%	1 4%
White	3 100%	5 83.3%	6 100%	6 100%	2 50%	22 88%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	3 100%	6 100%	6 100%	6 100%	4 100%	25 100%
The Abbreviated Injury Scale (AIS) (Count of Participants)
Count of Participants [Participants]	3 100%	6 100%	6 100%	6 100%	4 100%	25 100%

Outcome Measures

1. Primary Outcome

Title	Number of Adverse Events Within 1 Year (365 Days) That Are Related to AST-OPC1 Injection
Description	Numbers of adverse events within 1 year (365 days) that are related to AST-OPC1 injection
Time Frame	One Year

Outcome Measure Data

Analysis Population Description

All 25 subject experienced at least one (1) AEs. The population description described on comment [1] above.

Arm/Group Title	AST-OPC1, Cohort 1	AST-OPC1, Cohort 2	AST-OPC1, Cohort 3	AST-OPC1, Cohort 4	AST-OPC1, Cohort 5
Arm/Group Description	n=3 Dosage of 2 million cells AIS score A	n=6 Dosage of 10 million cells AIS score A	n=6 Dosage of 20 million cells AIS score A	n=6 Dosage of 10 million cells AIS score B	n=4 Dosage of 20 million cells AIS score B
Measure Participants	3	6	6	6	4
Number [Adverse Events]	92	122	133	118	69

2. Secondary Outcome

Title	Neurological Function as Measured by Upper Extremity Motor Scores and Motor Level on International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) Examinations as Secondary End Point - 365 Days After Injection of AST-OPC1
Description	The scale is based on the ISNCSCI (International Standards for Neurological Classification of Spinal Cord Injury) that measures the severity of Spinal cord injury. The data was collected per time point during the first year (30,60,90,180,270,365). The 365-days time point was pre-specified as Secondary Outcome Measure. High score means better outcome. Units are "Scores on a scale". The score is divided to motor scale (0-100) and sensor scale (0-224). Motor scale is divided to subscale of upper extremity (0-50) and lower extremity (0-50). Upper and lower extremity are divided to subscale of Right (0-25) + Left (0-25). Each upper & lower extremity is divided to subscale of 5 motor nerve function (0-5). Sensor scale is divided to subscale of light touch (0-112) and pin prick (0-112). light touch and pin prick are divided to subscales of Right (0-56) + Left (0-56). Each right and left light touch and pin prick are divided to subscales of 28 sensor nerve function (0-2)
Time Frame	One Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AST-OPC1, Cohort 1	AST-OPC1, Cohort 2	AST-OPC1, Cohort 3	AST-OPC1, Cohort 4	AST-OPC1, Cohort 5
Arm/Group Description	n=3 Dosage of 2 million AIS A	n=6 Dosage of 10 million AIS A	n=6 Dosage of 20 million AIS A	n=6 Dosage of 10 million AIS B	n=4 Dosage of 20 million AIS B
Measure Participants	3	6	6	6	4
UEMS (Upper Extremities Motor Scale) - Baseline	19	21	17	22	18
UEMS (Upper Extremities Motor Scale) - Day 365	24	34	26	28	24
LEMS (Lower Extremities Motor Scale) - Baseline	0	0	0	0	0
LEMS (Lower Extremities Motor Scale) - Day 365	0	0	0	1	1
LT (Light Touch) - Baseline	21	27	22	35	53
LT (Light Touch) - Day 365	21	32	31	46	65
PP (Pin Prick) - Baseline	22	23	19	25	22
PP (Pin Prick) - Day 365	20	25	21	28	34

Adverse Events

Time Frame	1 year
Arm/Group Title	AST-OPC1, Cohort 1		AST-OPC1, Cohort 2		AST-OPC1, Cohort 3		AST-OPC1, Cohort 4		AST-OPC1, Cohort 5
Arm/Group Description	n=3 Dosage of 2 million cells AIS score A		n=6 Dosage of 10 million cells AIS score A		n=6 Dosage of 20 million cells AIS score A		n=6 Dosage of 10 million cells AIS score B		n=4 Dosage of 20 million cells AIS score B
All Cause Mortality
	AST-OPC1, Cohort 1		AST-OPC1, Cohort 2		AST-OPC1, Cohort 3		AST-OPC1, Cohort 4		AST-OPC1, Cohort 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)
Serious Adverse Events
	AST-OPC1, Cohort 1		AST-OPC1, Cohort 2		AST-OPC1, Cohort 3		AST-OPC1, Cohort 4		AST-OPC1, Cohort 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)		2/6 (33.3%)		4/6 (66.7%)		2/6 (33.3%)		1/4 (25%)
Blood and lymphatic system disorders
Hypokalemia	0/3 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/4 (0%)	0
Cardiac disorders
Atrial Fibrillation	0/3 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/4 (25%)	1
Gastrointestinal disorders
Bilateral Decubitus Ulcers	0/3 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/4 (0%)	0
Gastrointestinal Bleeding	0/3 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/4 (0%)	0
General disorders
Altered Mental Status	0/3 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	2	0/6 (0%)	0	0/4 (0%)	0
Infections and infestations
Aspiration Pneumonia	0/3 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/4 (0%)	0
Bilateral Pyelonephritis due to UTI	0/3 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/4 (0%)	0
Buttock Abscess	0/3 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/4 (0%)	0
Escherichia Coli Urinary Sepsis	0/3 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/4 (0%)	0
Infected Epidural Fluid	0/3 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/4 (0%)	0
Sepsis	1/3 (33.3%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/4 (0%)	0
Urosepsis	0/3 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/4 (0%)	0
Urinary Tract Infection (UTI)	2/3 (66.7%)	2	1/6 (16.7%)	1	2/6 (33.3%)	2	2/6 (33.3%)	2	0/4 (0%)	0
Wound Infection	0/3 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/4 (0%)	0
Injury, poisoning and procedural complications
Cerebrospinal Fluid Leak	0/3 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/4 (0%)	0
Musculoskeletal and connective tissue disorders
Bilateral Hip Effusions	0/3 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/4 (0%)	0
Left Femoral Shaft Fracture	1/3 (33.3%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/4 (0%)	0
Renal and urinary disorders
Acute Renal Failure	0/3 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/4 (0%)	0
Non-Traumatic Kidney Injury	0/3 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/4 (25%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/3 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/4 (0%)	0
Vascular disorders
Pulmonary Embolism	0/3 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	2	0/6 (0%)	0	0/4 (0%)	0
Other (Not Including Serious) Adverse Events
	AST-OPC1, Cohort 1		AST-OPC1, Cohort 2		AST-OPC1, Cohort 3		AST-OPC1, Cohort 4		AST-OPC1, Cohort 5
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/4 (0%)

Limitations/Caveats

Open label study

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.