Cervical Spinal Cord Injury, Spinal Cord Trauma, Spine Injury
Conditions
Keywords
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
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).
Interventions
BIOLOGICALAST-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
Sponsors
Lineage Cell Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AST-OPC1, Cohort 1 n=3 Dosage of 2 million cells AIS score A | 3 |
| AST-OPC1, Cohort 2 n=6 Dosage of 10 million cells AIS score A | 6 |
| AST-OPC1, Cohort 3 n=6 Dosage of 20 million cells AIS score A | 6 |
| AST-OPC1, Cohort 4 n=6 Dosage of 10 million cells AIS score B | 6 |
| AST-OPC1, Cohort 5 n=4 Dosage of 20 million cells AIS score B | 4 |
| Total | 25 |
Baseline characteristics
| Characteristic | AST-OPC1, Cohort 1 | AST-OPC1, Cohort 2 | AST-OPC1, Cohort 3 | AST-OPC1, Cohort 4 | AST-OPC1, Cohort 5 | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 6 Participants | 6 Participants | 6 Participants | 4 Participants | 25 Participants |
| Age, Continuous | 24.3 years STANDARD_DEVIATION 6.1 | 24.5 years STANDARD_DEVIATION 7.4 | 44.7 years STANDARD_DEVIATION 14.7 | 28.5 years STANDARD_DEVIATION 14.1 | 34.3 years STANDARD_DEVIATION 20.7 | 30.8 years STANDARD_DEVIATION 14.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 5 Participants | 6 Participants | 6 Participants | 2 Participants | 22 Participants |
| Region of Enrollment United States | 3 participants | 6 participants | 6 participants | 6 participants | 4 participants | 25 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 5 Participants | 6 Participants | 2 Participants | 21 Participants |
| The Abbreviated Injury Scale (AIS) | 3 Participants | 6 Participants | 6 Participants | 6 Participants | 4 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 4 |
| other Total, other adverse events | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 4 |
| serious Total, serious adverse events | 2 / 3 | 2 / 6 | 4 / 6 | 2 / 6 | 1 / 4 |
Outcome results
Primary
Number of Adverse Events Within 1 Year (365 Days) That Are Related to AST-OPC1 Injection
Numbers of adverse events within 1 year (365 days) that are related to AST-OPC1 injection
Time frame: One Year
Population: All 25 subject experienced at least one (1) AEs. The population description described on comment \[1\] above.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AST-OPC1, Cohort 1 | Number of Adverse Events Within 1 Year (365 Days) That Are Related to AST-OPC1 Injection | 92 Adverse Events |
| AST-OPC1, Cohort 2 | Number of Adverse Events Within 1 Year (365 Days) That Are Related to AST-OPC1 Injection | 122 Adverse Events |
| AST-OPC1, Cohort 3 | Number of Adverse Events Within 1 Year (365 Days) That Are Related to AST-OPC1 Injection | 133 Adverse Events |
| AST-OPC1, Cohort 4 | Number of Adverse Events Within 1 Year (365 Days) That Are Related to AST-OPC1 Injection | 118 Adverse Events |
| AST-OPC1, Cohort 5 | Number of Adverse Events Within 1 Year (365 Days) That Are Related to AST-OPC1 Injection | 69 Adverse Events |
Secondary
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
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
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| AST-OPC1, Cohort 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 | UEMS (Upper Extremities Motor Scale) - Baseline | 19 Score on a scale |
| AST-OPC1, Cohort 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 | UEMS (Upper Extremities Motor Scale) - Day 365 | 24 Score on a scale |
| AST-OPC1, Cohort 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 | LEMS (Lower Extremities Motor Scale) - Baseline | 0 Score on a scale |
| AST-OPC1, Cohort 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 | LEMS (Lower Extremities Motor Scale) - Day 365 | 0 Score on a scale |
| AST-OPC1, Cohort 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 | LT (Light Touch) - Baseline | 21 Score on a scale |
| AST-OPC1, Cohort 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 | LT (Light Touch) - Day 365 | 21 Score on a scale |
| AST-OPC1, Cohort 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 | PP (Pin Prick) - Baseline | 22 Score on a scale |
| AST-OPC1, Cohort 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 | PP (Pin Prick) - Day 365 | 20 Score on a scale |
| AST-OPC1, Cohort 2 | 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 | LEMS (Lower Extremities Motor Scale) - Baseline | 0 Score on a scale |
| AST-OPC1, Cohort 2 | 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 | LT (Light Touch) - Day 365 | 32 Score on a scale |
| AST-OPC1, Cohort 2 | 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 | UEMS (Upper Extremities Motor Scale) - Baseline | 21 Score on a scale |
| AST-OPC1, Cohort 2 | 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 | LEMS (Lower Extremities Motor Scale) - Day 365 | 0 Score on a scale |
| AST-OPC1, Cohort 2 | 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 | UEMS (Upper Extremities Motor Scale) - Day 365 | 34 Score on a scale |
| AST-OPC1, Cohort 2 | 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 | PP (Pin Prick) - Day 365 | 25 Score on a scale |
| AST-OPC1, Cohort 2 | 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 | LT (Light Touch) - Baseline | 27 Score on a scale |
| AST-OPC1, Cohort 2 | 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 | PP (Pin Prick) - Baseline | 23 Score on a scale |
| AST-OPC1, Cohort 3 | 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 | PP (Pin Prick) - Baseline | 19 Score on a scale |
| AST-OPC1, Cohort 3 | 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 | PP (Pin Prick) - Day 365 | 21 Score on a scale |
| AST-OPC1, Cohort 3 | 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 | LEMS (Lower Extremities Motor Scale) - Day 365 | 0 Score on a scale |
| AST-OPC1, Cohort 3 | 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 | LT (Light Touch) - Day 365 | 31 Score on a scale |
| AST-OPC1, Cohort 3 | 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 | LEMS (Lower Extremities Motor Scale) - Baseline | 0 Score on a scale |
| AST-OPC1, Cohort 3 | 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 | UEMS (Upper Extremities Motor Scale) - Day 365 | 26 Score on a scale |
| AST-OPC1, Cohort 3 | 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 | UEMS (Upper Extremities Motor Scale) - Baseline | 17 Score on a scale |
| AST-OPC1, Cohort 3 | 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 | LT (Light Touch) - Baseline | 22 Score on a scale |
| AST-OPC1, Cohort 4 | 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 | UEMS (Upper Extremities Motor Scale) - Day 365 | 28 Score on a scale |
| AST-OPC1, Cohort 4 | 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 | LEMS (Lower Extremities Motor Scale) - Baseline | 0 Score on a scale |
| AST-OPC1, Cohort 4 | 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 | LEMS (Lower Extremities Motor Scale) - Day 365 | 1 Score on a scale |
| AST-OPC1, Cohort 4 | 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 | LT (Light Touch) - Baseline | 35 Score on a scale |
| AST-OPC1, Cohort 4 | 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 | LT (Light Touch) - Day 365 | 46 Score on a scale |
| AST-OPC1, Cohort 4 | 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 | PP (Pin Prick) - Day 365 | 28 Score on a scale |
| AST-OPC1, Cohort 4 | 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 | UEMS (Upper Extremities Motor Scale) - Baseline | 22 Score on a scale |
| AST-OPC1, Cohort 4 | 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 | PP (Pin Prick) - Baseline | 25 Score on a scale |
| AST-OPC1, Cohort 5 | 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 | LEMS (Lower Extremities Motor Scale) - Day 365 | 1 Score on a scale |
| AST-OPC1, Cohort 5 | 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 | PP (Pin Prick) - Day 365 | 34 Score on a scale |
| AST-OPC1, Cohort 5 | 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 | LEMS (Lower Extremities Motor Scale) - Baseline | 0 Score on a scale |
| AST-OPC1, Cohort 5 | 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 | PP (Pin Prick) - Baseline | 22 Score on a scale |
| AST-OPC1, Cohort 5 | 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 | UEMS (Upper Extremities Motor Scale) - Baseline | 18 Score on a scale |
| AST-OPC1, Cohort 5 | 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 | LT (Light Touch) - Day 365 | 65 Score on a scale |
| AST-OPC1, Cohort 5 | 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 | UEMS (Upper Extremities Motor Scale) - Day 365 | 24 Score on a scale |
| AST-OPC1, Cohort 5 | 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 | LT (Light Touch) - Baseline | 53 Score on a scale |