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

• NIHSS response [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
• Adverse events [ Time Frame: Day 90 ] [ Designated as safety issue: Yes ]
• Modified Rankin Score [ Time Frame: Day 90 ] [ Designated as safety issue: No ]

• NIHSS Response >=4 at Day 90 [ Time Frame: Baseline and Day 90 ] [ Designated as safety issue: No ]
  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 [ Time Frame: Baseline and Day 30 ] [ Designated as safety issue: No ]
  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 [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
  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 [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
  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.
• Action Research Arm Test (ARAT) Change From Baseline at Day 90 [ Time Frame: Baseline and Day 90 ] [ Designated as safety issue: No ]
  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.
• Gait Velocity Test Change From Baseline at Day 90 [ Time Frame: Baseline and Day 90 ] [ Designated as safety issue: No ]
  The Gait Velocity Test assesses ability to walk as measured by the time (seconds) it takes a patient to walk 10 meters.
• Boston Naming Test (BNT) Change From Baseline at Day 90 [ Time Frame: Baseline and Day 90 ] [ Designated as safety issue: No ]
  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.
• Line Cancellation Test Change From Baseline at Day 90 [ Time Frame: Baseline and Day 90 ] [ Designated as safety issue: No ]
  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 [ Time Frame: Baseline and Day 90 ] [ Designated as safety issue: No ]
  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 [ Time Frame: Baseline and Day 90 ] [ Designated as safety issue: No ]
  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 [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
  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.

• Barthel index [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
• Action Research Arm Test [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
• Gait Velocity Test [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
• Boston Naming Test [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
• Line Cancellation Test [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
• Trails A & B Test [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
• Geriatric Depression Scale [ Time Frame: Day 90 ] [ Designated as safety issue: No ]

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.

• Drug: human 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
  Other Names:

  • Ovidrel
  • Ovitrelle
  • Epogen
  • Eprex
• Drug: human 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 12,000 IU, IV, on Day 7, 8, and 9 of study participation
  Other Names:

  • Ovidrel
  • Ovitrelle
  • Epogen
  • Eprex
• Drug: human 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 20,000 IU, IV, on Day 7, 8, and 9 of study participation
  Other Names:

  • Ovidrel
  • Ovitrelle
  • Epogen
  • Eprex
• Drug: 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
  Other Name: Sodium Chloride 0.9%

• Experimental: NTx®-265 Low Dose
  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
  Intervention: Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO)
• Experimental: 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
  Intervention: Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO)
• Experimental: 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
  Intervention: Drug: human chorionic gonadotropin (hCG), then epoetin alfa (EPO)
• Placebo Comparator: Saline Placebo
  Intervention: Drug: Saline Placebo

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