Study of NTx®-265: Human Chorionic Gonadotropin (hCG) and Epoetin Alfa (EPO) in Acute Ischemic Stroke Patients

Study Overview
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Brief Summary
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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.

Official Title
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A Phase IIb Prospective, Randomized, Double-blind, Placebo Controlled, Multicenter, Dose Escalation Study of NTx®-265: Human Chorionic Gonadotropin (hCG) and Epoetin Alfa (EPO) in Acute Ischemic Stroke Patients (REGENESIS-LED)

Conditions
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Stroke

Intervention / Treatment
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* Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO)
* Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO)
* Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO)
* Drug: Saline Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NTx®-265 Low Dose<br>hCG 385 µg (10,000 international unit [IU]), subcutaneously (SC), on Day 1, 3 and 5 of study participation, then EPO 4,000 IU, intravenously (IV), on Day 7, 8, and 9 of study participation | Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO)<br>* 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<br>* Other names: Eprex;|
| Experimental: NTx®-265 Medium Dose<br>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 | Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO)<br>* 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<br>* Other names: Eprex;|
| Experimental: NTx®-265 High Dose<br>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 | Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO)<br>* 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<br>* Other names: Eprex;|
| Placebo Comparator: Saline Placebo<br> | Drug: Saline Placebo<br>* Saline SC, on Day 1, 3, and 5 of study participation, then Saline IV, on Day 7, 8, and 9 of study participation<br>* Other names: Sodium Chloride 0.9%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline and Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and Day 90 | 
| 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). | Baseline and Day 30 | 
| 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. | Day 90 | 
| 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. | Day 90 | 
| 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. | Baseline and Day 90 | 
| 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. | Baseline and Day 90 | 
| 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. | Baseline and Day 90 | 
| 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. | Baseline and Day 90 | 
| 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…) | Baseline and Day 90 | 
| 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) | Baseline and Day 90 | 
| 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. | Day 90 |