Stroke
Conditions
Brief summary
The purpose of this study is: * To assess the neurological outcome in acute ischemic stroke patients treated with NTx®-265, when compared with patients given a placebo control. * To assess the safety and tolerability of NTx®-265 when given to acute ischemic stroke patients.
Interventions
DRUGSaline Placebo
Saline SC, on Day 1, 3, and 5 of study participation, then Saline IV, on Day 7, 8, and 9 of study participation
DRUGhuman chorionic gonadotropin (hCG), then epoetin alfa (EPO)
hCG 385 µg (10,000 IU), SC, on Day 1, 3 and 5 of study participation, then EPO 4,000 IU, IV, on Day 7, 8, and 9 of study participation
Sponsors
Stem Cell Therapeutics Corp.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-85 * NIHSS score 8-20 * Stroke is ischemic in origin, supratentorial, and radiologically confirmed * Patient is 24-48 hours from time of stroke onset when the first dose of NTx®-265 therapy is administered * Reasonable expectation of availability to receive the full 9 day NTx®- 265 therapy and subsequent follow-up visits * Reasonable expectation that patient will receive standard post-stroke physical, occupational, speech, and cognitive therapy as indicated * Female patient is either not of childbearing potential or agrees to use two of the effective separate non-hormonal forms of contraception throughout the study
Exclusion criteria
* Patients presenting with lacunar, hemorrhagic and/or brain stem stroke * Patients who have received tissue plasminogen activator (tPA)following the index stroke * Patients classified as comatose * Women who have tested positive for pregnancy, or are breast-feeding, or are not using a birth control * Serum hemoglobin \> 16 grams(g)/deciliter (dL)(males) or \> 14 g/dL (females); or platelet count \> 400,000/cubic millimeters(mm3) * Advanced liver, kidney, cardiac, or pulmonary disease * Elevated serum bilirubin,alkaline phosphatase, aspartate aminotransferase (AST) or alanine transaminase (ALT),creatinine, or prostate-specific antigen (PSA) levels * Patients with a known history of hypercoagulability * Expected survival \< 1 year * Allergy or other contraindication to hCG or EPO * A known diagnosis of cancer in the previous 5 years * Uncontrolled hypertension * Use of either hCG or epoetin alfa within the previous 90 days * Any condition known to elevate hCG * Patients with a pre-stroke/pre-morbid modified Rankin Score (mRS)≥ 2 * Any patients not living independently * Any other medical condition or degree of stroke such that, in the investigator's opinion, the patient should not be included in the trial * With the exception of the qualifying stroke, any other stroke within the previous 3 months * Patients who cannot take anti-platelet or anti-coagulant therapy * Pre-existing and active major psychiatric or other chronic neurological disease * Alcohol abuse or have a history of substance abuse or dependency within 12 months prior to the study * Currently participating in another investigational study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| National Institutes of Health Stroke Scale (NIHSS) Change From Baseline at Day 90 | Baseline and Day 90 | The NIHSS is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from 0 (no deficit) to 42 (dead). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Boston Naming Test (BNT) Change From Baseline at Day 90 | Baseline and Day 90 | The BNT assesses impairment of language ability by asking patients to identify 20 different pictures each time the test is taken. A score of 20 is best, 0 is worst. |
| NIHSS Response >=4 at Day 90 | Baseline and Day 90 | The NIHSS is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from 0 (no deficit) to 42 (dead). NIHSS Response \>=4 is defined as a \>=4 change from baseline at Day 90. |
| NIHSS Change From Baseline at Day 30 | Baseline and Day 30 | The NIHSS is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from 0 (no deficit) to 42 (dead). |
| Modified Rankin Scale (mRS) Response <=2 at Day 90 | Day 90 | The mRS measures the degree of disability or dependence in the daily activities of people who have suffered a stroke. The scale runs from 0 (perfect health without symptoms) to 6 (dead). mRS response \<=2 is defined as the mRS score \<=2 at Day 90. |
| Barthel Index at Day 90 | Day 90 | The Barthel Index measures 10 activities of daily living and mobility. A score of 100 = is best (able to live at home with a degree of independence), 0 is worst. |
| Gait Velocity Test Change From Baseline at Day 90 | Baseline and Day 90 | The Gait Velocity Test assesses ability to walk as measured by the time (seconds) it takes a patient to walk 10 meters. |
| Line Cancellation Test Change From Baseline at Day 90 | Baseline and Day 90 | The Line Cancellation Test detects the loss of awareness of one side of the body. A score of 0.00 (no units) is normal (patient favors neither right nor left side). A score of +1.00 indicates severe unawareness of the left side. A score of -1.00 indicates severe unawareness of the right side. |
| Trails A Test Change From Baseline at Day 90 | Baseline and Day 90 | The Trails A test measures visual scanning, numeric sequencing, and visual-motor coordination; the test score is the time (seconds) required to connect 25 numbers (e.g., 1, 2, 3, 4…) |
| Trails B Test Change From Baseline at Day 90 | Baseline and Day 90 | The Trails B test measures visual scanning, numeric sequencing, and visual-motor coordination; the test score is the time (seconds) required to connect 25 alpha numeric circles (e.g., 1, A, 2, B, 3, C, 4, D) |
| Geriatric Depression Scale at Day 90 | Day 90 | The Geriatric Depression Scale is commonly used to assess depression in stroke patients of any age by asking 15 yes/no questions, and then scored. A score of 0 - 5 is normal, whereas a score of 6 -15 suggests depression. |
| Action Research Arm Test (ARAT) Change From Baseline at Day 90 | Baseline and Day 90 | The ARAT assesses recovery of arm function following stroke through a series of subtests judging ability to grasp, grip, pinch, or move the arm; scores are on a scale; The total maximum (best) score is 57 and the total minimum (worst) score is 0. |
Countries
Canada, India, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NTx®-265 Low Dose hCG 385 µg (10,000 IU), SC, on Day 1, 3 and 5 of study participation, then EPO 4,000 IU, IV, on Day 7, 8, and 9 of study participation | 24 |
| NTx®-265 Medium Dose hCG 385 µg (10,000 IU), SC, on Day 1, 3 and 5 of study participation, then EPO 12,000 IU, IV, on Day 7, 8, and 9 of study participation | 24 |
| NTx®-265 High Dose hCG 385 µg (10,000 IU), SC, on Day 1, 3 and 5 of study participation, then EPO 20,000 IU, IV, on Day 7, 8, and 9 of study participation | 24 |
| Saline Placebo saline SC, on Day 1, 3 and 5 of study participation, then saline IV, on Day 7, 8, and 9 of study participation | 24 |
| Total | 96 |
Baseline characteristics
| Characteristic | NTx®-265 Low Dose | NTx®-265 Medium Dose | NTx®-265 High Dose | Saline Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 7 Participants | 7 Participants | 12 Participants | 29 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 17 Participants | 17 Participants | 12 Participants | 67 Participants |
| Age Continuous | 57.42 years STANDARD_DEVIATION 10.49 | 58.58 years STANDARD_DEVIATION 13.32 | 54.83 years STANDARD_DEVIATION 12.98 | 61.67 years STANDARD_DEVIATION 12.38 | 58.13 years STANDARD_DEVIATION 12.39 |
| Region of Enrollment Canada | 0 participants | 2 participants | 0 participants | 0 participants | 2 participants |
| Region of Enrollment India | 24 participants | 22 participants | 24 participants | 24 participants | 94 participants |
| Sex: Female, Male Female | 18 Participants | 14 Participants | 17 Participants | 16 Participants | 65 Participants |
| Sex: Female, Male Male | 6 Participants | 10 Participants | 7 Participants | 8 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 24 | 19 / 24 | 2 / 24 | 10 / 24 |
| serious Total, serious adverse events | 2 / 24 | 4 / 24 | 3 / 24 | 2 / 24 |
Outcome results
Primary
National Institutes of Health Stroke Scale (NIHSS) Change From Baseline at Day 90
The NIHSS is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from 0 (no deficit) to 42 (dead).
Time frame: Baseline and Day 90
Population: The analysis was conducted using a modified Intent-to-Treat population, defined as all randomized patients who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTx®-265 Low Dose | National Institutes of Health Stroke Scale (NIHSS) Change From Baseline at Day 90 | 6.79 scores on a scale | Standard Deviation 4.22 |
| NTx®-265 Medium Dose | National Institutes of Health Stroke Scale (NIHSS) Change From Baseline at Day 90 | 6.50 scores on a scale | Standard Deviation 4.53 |
| NTx®-265 High Dose | National Institutes of Health Stroke Scale (NIHSS) Change From Baseline at Day 90 | 6.08 scores on a scale | Standard Deviation 3.3 |
| Saline Placebo | National Institutes of Health Stroke Scale (NIHSS) Change From Baseline at Day 90 | 7.17 scores on a scale | Standard Deviation 4.24 |
Secondary
Action Research Arm Test (ARAT) Change From Baseline at Day 90
The ARAT assesses recovery of arm function following stroke through a series of subtests judging ability to grasp, grip, pinch, or move the arm; scores are on a scale; The total maximum (best) score is 57 and the total minimum (worst) score is 0.
Time frame: Baseline and Day 90
Population: Not all patients enrolled in the group completed this outcome measure.~The analysis was conducted using a modified Intent-to-Treat population, defined as all randomized patients who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTx®-265 Low Dose | Action Research Arm Test (ARAT) Change From Baseline at Day 90 | 10.67 scores on a scale | Standard Deviation 13.37 |
| NTx®-265 Medium Dose | Action Research Arm Test (ARAT) Change From Baseline at Day 90 | 33.50 scores on a scale | Standard Deviation 26.12 |
| NTx®-265 High Dose | Action Research Arm Test (ARAT) Change From Baseline at Day 90 | 30.33 scores on a scale | Standard Deviation 16.8 |
| Saline Placebo | Action Research Arm Test (ARAT) Change From Baseline at Day 90 | 23.75 scores on a scale | Standard Deviation 20.27 |
Secondary
Barthel Index at Day 90
The Barthel Index measures 10 activities of daily living and mobility. A score of 100 = is best (able to live at home with a degree of independence), 0 is worst.
Time frame: Day 90
Population: The analysis was conducted using a modified Intent-to-Treat population, defined as all randomized patients who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTx®-265 Low Dose | Barthel Index at Day 90 | 68.18 Scores on a scale | Standard Deviation 29.62 |
| NTx®-265 Medium Dose | Barthel Index at Day 90 | 80.17 Scores on a scale | Standard Deviation 22.04 |
| NTx®-265 High Dose | Barthel Index at Day 90 | 85.25 Scores on a scale | Standard Deviation 20.28 |
| Saline Placebo | Barthel Index at Day 90 | 90.89 Scores on a scale | Standard Deviation 12.69 |
Secondary
Boston Naming Test (BNT) Change From Baseline at Day 90
The BNT assesses impairment of language ability by asking patients to identify 20 different pictures each time the test is taken. A score of 20 is best, 0 is worst.
Time frame: Baseline and Day 90
Population: Not all patients enrolled in the group completed this outcome measure.~The analysis was conducted using a modified Intent-to-Treat population, defined as all randomized patients who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTx®-265 Low Dose | Boston Naming Test (BNT) Change From Baseline at Day 90 | 3.93 Scores on a scale | Standard Deviation 3.1 |
| NTx®-265 Medium Dose | Boston Naming Test (BNT) Change From Baseline at Day 90 | 4.17 Scores on a scale | Standard Deviation 4.11 |
| NTx®-265 High Dose | Boston Naming Test (BNT) Change From Baseline at Day 90 | 0.20 Scores on a scale | Standard Deviation 2.74 |
| Saline Placebo | Boston Naming Test (BNT) Change From Baseline at Day 90 | 3.69 Scores on a scale | Standard Deviation 3.82 |
Secondary
Gait Velocity Test Change From Baseline at Day 90
The Gait Velocity Test assesses ability to walk as measured by the time (seconds) it takes a patient to walk 10 meters.
Time frame: Baseline and Day 90
Population: Not all patients enrolled in the group completed this outcome measure.~The analysis was conducted using a modified Intent-to-Treat population, defined as all randomized patients who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTx®-265 Low Dose | Gait Velocity Test Change From Baseline at Day 90 | -22.75 seconds | Standard Deviation 41.6 |
| NTx®-265 Medium Dose | Gait Velocity Test Change From Baseline at Day 90 | -50.33 seconds | Standard Deviation 48.95 |
| NTx®-265 High Dose | Gait Velocity Test Change From Baseline at Day 90 | -6.40 seconds | Standard Deviation 7.37 |
| Saline Placebo | Gait Velocity Test Change From Baseline at Day 90 | -53.80 seconds | Standard Deviation 54.15 |
Secondary
Geriatric Depression Scale at Day 90
The Geriatric Depression Scale is commonly used to assess depression in stroke patients of any age by asking 15 yes/no questions, and then scored. A score of 0 - 5 is normal, whereas a score of 6 -15 suggests depression.
Time frame: Day 90
Population: Not all patients enrolled in the group completed this outcome measure.~The analysis was conducted using a modified Intent-to-Treat population, defined as all randomized patients who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTx®-265 Low Dose | Geriatric Depression Scale at Day 90 | 7.25 scores on a scale | Standard Deviation 4.24 |
| NTx®-265 Medium Dose | Geriatric Depression Scale at Day 90 | 3.88 scores on a scale | Standard Deviation 3.08 |
| NTx®-265 High Dose | Geriatric Depression Scale at Day 90 | 3.56 scores on a scale | Standard Deviation 2.77 |
| Saline Placebo | Geriatric Depression Scale at Day 90 | 4.74 scores on a scale | Standard Deviation 3.9 |
Secondary
Line Cancellation Test Change From Baseline at Day 90
The Line Cancellation Test detects the loss of awareness of one side of the body. A score of 0.00 (no units) is normal (patient favors neither right nor left side). A score of +1.00 indicates severe unawareness of the left side. A score of -1.00 indicates severe unawareness of the right side.
Time frame: Baseline and Day 90
Population: Not all patients enrolled in the group completed this outcome measure.~The analysis was conducted using a modified Intent-to-Treat population, defined as all randomized patients who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTx®-265 Low Dose | Line Cancellation Test Change From Baseline at Day 90 | -0.03 scores on a scale | Standard Deviation 0.03 |
| NTx®-265 Medium Dose | Line Cancellation Test Change From Baseline at Day 90 | -0.07 scores on a scale | Standard Deviation 0.11 |
| NTx®-265 High Dose | Line Cancellation Test Change From Baseline at Day 90 | -0.04 scores on a scale | Standard Deviation 0.1 |
| Saline Placebo | Line Cancellation Test Change From Baseline at Day 90 | -0.00 scores on a scale | Standard Deviation 0.16 |
Secondary
Modified Rankin Scale (mRS) Response <=2 at Day 90
The mRS measures the degree of disability or dependence in the daily activities of people who have suffered a stroke. The scale runs from 0 (perfect health without symptoms) to 6 (dead). mRS response \<=2 is defined as the mRS score \<=2 at Day 90.
Time frame: Day 90
Population: The analysis was conducted using a modified Intent-to-Treat population, defined as all randomized patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NTx®-265 Low Dose | Modified Rankin Scale (mRS) Response <=2 at Day 90 | response (mRS <=2) | 11 participants |
| NTx®-265 Low Dose | Modified Rankin Scale (mRS) Response <=2 at Day 90 | No response (mRS > 2) | 13 participants |
| NTx®-265 Medium Dose | Modified Rankin Scale (mRS) Response <=2 at Day 90 | No response (mRS > 2) | 13 participants |
| NTx®-265 Medium Dose | Modified Rankin Scale (mRS) Response <=2 at Day 90 | response (mRS <=2) | 11 participants |
| NTx®-265 High Dose | Modified Rankin Scale (mRS) Response <=2 at Day 90 | response (mRS <=2) | 15 participants |
| NTx®-265 High Dose | Modified Rankin Scale (mRS) Response <=2 at Day 90 | No response (mRS > 2) | 9 participants |
| Saline Placebo | Modified Rankin Scale (mRS) Response <=2 at Day 90 | response (mRS <=2) | 18 participants |
| Saline Placebo | Modified Rankin Scale (mRS) Response <=2 at Day 90 | No response (mRS > 2) | 6 participants |
Secondary
NIHSS Change From Baseline at Day 30
The NIHSS is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from 0 (no deficit) to 42 (dead).
Time frame: Baseline and Day 30
Population: The analysis was conducted using a modified Intent-to-Treat population, defined as all randomized patients who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTx®-265 Low Dose | NIHSS Change From Baseline at Day 30 | 4.67 scores on a scale | Standard Deviation 4.53 |
| NTx®-265 Medium Dose | NIHSS Change From Baseline at Day 30 | 4.29 scores on a scale | Standard Deviation 3.37 |
| NTx®-265 High Dose | NIHSS Change From Baseline at Day 30 | 5.00 scores on a scale | Standard Deviation 2.98 |
| Saline Placebo | NIHSS Change From Baseline at Day 30 | 5.33 scores on a scale | Standard Deviation 3.33 |
Secondary
NIHSS Response >=4 at Day 90
The NIHSS is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. Values range from 0 (no deficit) to 42 (dead). NIHSS Response \>=4 is defined as a \>=4 change from baseline at Day 90.
Time frame: Baseline and Day 90
Population: The analysis was conducted using a modified Intent-to-Treat population, defined as all randomized patients who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| NTx®-265 Low Dose | NIHSS Response >=4 at Day 90 | No Response (<4) | 6 participants |
| NTx®-265 Low Dose | NIHSS Response >=4 at Day 90 | Response (>=4) | 18 participants |
| NTx®-265 Medium Dose | NIHSS Response >=4 at Day 90 | Response (>=4) | 17 participants |
| NTx®-265 Medium Dose | NIHSS Response >=4 at Day 90 | No Response (<4) | 7 participants |
| NTx®-265 High Dose | NIHSS Response >=4 at Day 90 | No Response (<4) | 5 participants |
| NTx®-265 High Dose | NIHSS Response >=4 at Day 90 | Response (>=4) | 19 participants |
| Saline Placebo | NIHSS Response >=4 at Day 90 | No Response (<4) | 5 participants |
| Saline Placebo | NIHSS Response >=4 at Day 90 | Response (>=4) | 19 participants |
Secondary
Trails A Test Change From Baseline at Day 90
The Trails A test measures visual scanning, numeric sequencing, and visual-motor coordination; the test score is the time (seconds) required to connect 25 numbers (e.g., 1, 2, 3, 4…)
Time frame: Baseline and Day 90
Population: Not all patients enrolled in the group completed this outcome measure.~The analysis was conducted using a modified Intent-to-Treat population, defined as all randomized patients who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTx®-265 Low Dose | Trails A Test Change From Baseline at Day 90 | -11.33 seconds | Standard Deviation 22.2 |
| NTx®-265 Medium Dose | Trails A Test Change From Baseline at Day 90 | -21.89 seconds | Standard Deviation 22.1 |
| NTx®-265 High Dose | Trails A Test Change From Baseline at Day 90 | -13.29 seconds | Standard Deviation 21.91 |
| Saline Placebo | Trails A Test Change From Baseline at Day 90 | -23.44 seconds | Standard Deviation 25.53 |
Secondary
Trails B Test Change From Baseline at Day 90
The Trails B test measures visual scanning, numeric sequencing, and visual-motor coordination; the test score is the time (seconds) required to connect 25 alpha numeric circles (e.g., 1, A, 2, B, 3, C, 4, D)
Time frame: Baseline and Day 90
Population: Not all patients enrolled in the group completed this outcome measure.~The analysis was conducted using a modified Intent-to-Treat population, defined as all randomized patients who received at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NTx®-265 Low Dose | Trails B Test Change From Baseline at Day 90 | -44.33 seconds | Standard Deviation 51.6 |
| NTx®-265 Medium Dose | Trails B Test Change From Baseline at Day 90 | -41.33 seconds | Standard Deviation 62.89 |
| NTx®-265 High Dose | Trails B Test Change From Baseline at Day 90 | -55.14 seconds | Standard Deviation 59.92 |
| Saline Placebo | Trails B Test Change From Baseline at Day 90 | -22.78 seconds | Standard Deviation 71.22 |